The ANKK1 Gene and its Possible Influence on Alcohol
The Role of Victimization and Parent-Child Relationship
Advanced level: Independent thesis work, 30 hp Advisor: Catherine Tuvblad
First of all, I really need to thank my advisor, Catherine Tuvblad, for always being patient, kind and quick to laugh during this process and for always making time for me at all hours and days of the week no matter what problem I was facing. Secondly, I want to thank all my classmates for their constructive criticism – without them this essay would not even be half as good. I also want to send out some extra appreciation to my former roommate (you know who you are!) for despairing about these essays with me and always being ready to bring out a bottle of wine. And last but not least, I need to thank my partner for putting up with my mood swings during this semester, you are a true saint!
Risky alcohol use increases the risk of certain crimes such as drunk driving, spousal abuse and fighting. Around 60% of an individual’s alcohol use is attributable to genetic influences, however little is known regarding the specific genes that are involved in increasing the risk of risky alcohol use. Recent theories posit that some genes are so called susceptibility genes, meaning that carriers of certain genes or alleles are more susceptible both to positive and negative environments. The aim of the present study was to examine main and interaction effects of a possible susceptibility gene (ANKK1, which in previous research has been found to be related to risky alcohol use), and victimization as a negative environmental factor and parent-child relationship as a positive factor. Data were drawn from the RESUME project, and in the present study, 1.800 participants were included (47% males; 53% females; mean age of 22.15 years). Results showed no statistically significant main or interaction effect for ANKK1, but a statistically significant main effect was found for victimization and parent-child relationship. In conclusion, future research should include a larger sample size and use participants diagnosed with alcohol dependency. In addition, the susceptibility properties of ANKKI needs to be further examined, as the results from the present study indicate that ANKK1 is not a susceptibility gene.
Keywords: the ANKK1 gene, alcohol use, gene x environment interaction, the differential-susceptibility hypothesis, the biological-sensitivity- to-context thesis
Riskfylld alkoholkonsumtion kan öka risken för att vissa brott begås, såsom rattfylleri, partnervåld och slagsmål. Forskning har visat att omkring 60% av en individs
alkoholkonsumtion kan förklaras av genetik, men det finns lite forskning kring just vilka gener som ökar risken för alkoholism. Nya teorier tror att vissa gener är så kallade
sårbarhetsgener, vilket innebära att individer som bär på dessa gener eller särskilda alleler är mer sårbara för både positiva och negativa miljöfaktorer. Syftet med den nuvarande studien var att undersöka huvud-och interaktionseffekter av en potentiell sårbarhetsgen (ANKK1, som tidigare forskning visat har en påverkan på riskfylld alkoholkonsumtion), med utsatthet som den negativa faktorn och barn-föräldrarelation som den positiva faktorn. Data i form av enkätsvar och DNA prov från RESUME studien användes för den nuvarande studien, där 1,800 deltagare inkluderades (47% män; 53% av kvinnor; medelålder = 22.15). Resultaten visade inte på någon statistiskt signifikant huvud-eller interaktionseffekt för ANKKI, men det fanns en statistiskt signifikant huvudeffekt för utsatthet och barn-föräldrarelation. Slutsatsens som dras är att framtida studier bör fokusera på att ha ett större urval och använda sig av deltagare som är diagnosticerade med alkoholmissbruk. Utöver det bör framtida forskning fortsätta undersöka om ANKK1 är en sårbarhetsgen, eftersom resultaten från denna studie visar att den inte är en sårbarhetsgen.
Nyckelord: ANKK1 genen, alkoholkonsumtion, gen x miljöinteraktion, differential-susceptibility hypothesis, biological-sensitivity- to-context thesis
List of Contents
Risky alcohol Use ...2
The ANKK1 Gene...2
Interaction between ANKK1 Polymorphism and Risky Alcohol Use………..3
Parent-Child Relationship and Victimization………6
Aim of Study and Hypothesis………..9
Method ... 10 Participants... 10 Measures ... 11 Procedure………..12 Ethics………...13 Genotyping………14 Statistical analysis………....14 Results………..15 Discussion……….19
Findings in the present study in relation to previous research……… 20
Findings in the present study in relation to theory………21
Strengths and Limitations………..22
Implications of the current study………..24
Alcoholism is a complex disorder and one of the most common illnesses the world is faced with today (Bhaskar et al, 2010). Risky alcohol use can lead to a row of bad consequences in an individual’s life, such as having a negative effect on relationships, work, studies and other obligations. Alcohol has also shown to be a moderating factor for crime, were several studies have shown that alcohol shortens your self-control and in combination with certain
personality traits it can also make a person more reckless and violent (Bromley & Nelson, 2002; Petrie, Doran, Shakeshaft & Sanson-Fisher, 2010; Richardson & Budd, 2003).
Violence against strangers and partners often increase in intensity if alcohol is consumed, as does harassment and drunk driving as these are most common amongst people that show a risky alcohol use. Alcoholism has shown to arise from interactions between genetic and environmental risk factors, and evidence from family, twin and adoption studies have shown that alcoholism is indeed genetically influenced, with a heritability around 50-60% (Swagell et al, 2012). Unlike other drugs such as marijuana, cocaine or heroin we know very little about alcohol's pathway in the brain, but alcohol has the potential to interact with many different proteins in our body compared to other drugs (Bhaskar et al, 2010). A genetic vulnerability to alcohol exists, and both human and animal model studies have shown that dopamine receptors plays a big role in the reward and reinforcement behavior system in our bodies. Alcohol has a powerful effect on dopamine activity in the brain, and when we drink the brains so called reward circuits are flooded with dopamine (Rhanes, 2015). However, over time alcohol can cause dopamine levels to plummet, leaving you feeling miserable and craving more alcohol to feel better. The Ankyrin Repeat and Kinase Domain Containing 1 gene (ANKK1) plays a role in diminishing our dopamine receptors, which could make the gene a candidate in susceptibility for alcoholism (Koeneke et al, 2020; Ponce et al, 2009). The “differential-susceptibility hypothesis” (Belsky & Pluess, 2009) and the “biological-sensitivity- to-context thesis” (Boyce & Ellis, 2005) are two overlapping but somewhat different theories that claim that individuals with susceptibility genes (such as ANKK1) are more susceptible in both a positive and negative environments. This means that certain individuals react more negatively in an adverse environment and flourish more in a positive one. Which makes it important to test both adverse and positive life experiences in relation to ANKK1 and risky alcohol use. Victimization and parent-child relationship have been shown in previous studies to have an effect on risky alcohol use (Branstetter, Furman & Cottrell, 2009; Branstetter & Furman, 2013; Mak & Iacovou, 2019; Miller, Downs & Testa, 1993; Marschall-Lévesque et al, 2017; Nayaj, Lown, Bond & Greenfield, 2012), but the question
remains if the ANKK1 gene plays a part in the outcome as a possible susceptibility gene. Study results surrounding the ANKK1 gene and risky alcohol use have shown varied results and made the gene controversial, but many factors also remain to be tested in interaction with ANKK1 (Swagell et al, 2012). The present study aims to examine potential main and
interaction effects of the ANKK1 gene, parent-child relationship, victimization and their effect on risky alcohol use.
Risky Alcohol Use
Risky alcohol use is the term that will be used in this study, instead of alcoholism or alcohol dependency, since there were so few participants in the present study sample that fit the criteria for alcohol dependency. Participants who displayed an unhealthy alcohol
consumption were instead considered to have a risky alcohol use. Risky alcohol use can be referred to as the harmful use of alcohol (World Health Organization, n.d.). There is no accepted universal definition, but one definition that is frequently cited is the one in DSM-V, which is the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders and issued by the American Psychiatric Association (Shiel, n.d.). Risky alcohol use is regarded in the DSM-V as a maladaptive pattern of substance use that leads to a row of consequences in the individual’s life. For example, it can result in failure to fulfill major obligations at work, at home or at school. Such as repeated absence, poor performance, possible suspensions or expulsions from school or neglect of children or the household. It can also be frequent substance use in situations where it is hazardous, such as driving a car or other heavy machinery. Or when the substance abuse leads to legal problems, such as arrests for
disorderly conduct, and when the use of the substance starts to impair social or interpersonal problems. Such as arguments with parents or spouse about their intoxication or when it leads to physical fights either with spouses, family or strangers and can lead to other criminal acts during intoxication.
The ANKK1 Gene
Since studies on risky alcohol use have found indications that 50-60% of the risk of developing risky alcohol use comes from heritable factors, there seems to be a genetic vulnerability at work (Swagell et al, 2012). A genetic vulnerability could rather be called a genetic predisposition, or a genetic susceptibility which is the term that will be used in the present study (U.S National Library of Medicine, 2020). Genetic susceptibility is an
increased likelihood of developing certain diseases or addictions based on a person’s specific genetic makeup. A genetic susceptibility results from specific genetic variations that are inherited from a parent. In the present study the ANKK1 gene will be examined, which is one
of the genes that is considered a candidate of susceptibility for addictive disorders, such as risky alcohol use (Koeneke et al, 2020; Ponce et al, 2009).
The ANKK1 gene is located in chromosome 11 in a human (start 113,387,779 bp and end 113,400,416 bp) (GeneCards, n.d; Koeneke et al, 2020). The ANKK1 gene is, amongst other things, involved in signal transduction pathways. Simply put signal transduction pathways convert extracellular stimuli into a specific cellular response (Costa, Giordano & Guizzetti, 2010). Meaning that signal transduction begins with a signal receptor and ends with a change in cell function, and eventually the signal creates a change in the cell either in the expression of the DNA or in the activity of enzymes. Abnormal signaling through communication pathways can however result in diseases, and signal transduction pathways are increasingly the target of drug development and addictions, such as risky alcohol use. The ANKK1 gene also contains a single nucleotide polymorphism called Taq1A (GeneCards, n.d; Koeneke et al, 2020). Genetic polymorphism is the occurrence in the same population of two or more alleles at one locus, each with appreciable frequency, in simpler terms one could say that the term genetic polymorphism describes the functionally silent differences in DNA sequence that make each human genome unique (Collins, n.d.).
The Taq1A polymorphism was previously thought to reside in the neighboring gene DRD2, though newer research has established that it lays just downstream of the DRD2 gene (Koeneke et al, 2020; SNPedia, 2019). Since the Taq1A polymorphism resides so close to the DRD2 dopamine gene it is thought to influence the DRD2 receptor expression, and it controls the synthesis of dopamine in the brain. As previously said, alcohol has a powerful effect on dopamine activity in the brain and when consumed it activates the so-called reward circuits in our brain, who then floods with dopamine (Rhanes, 2015). Over time, alcohol can cause dopamine levels to plummet, which leaves you feeling miserable and craving more alcohol to feel better. Every individual has the ANKK1 gene, but as previously mentioned, there are several alleles (Koeneke et al, 2020; Ponce et al, 2009). Individuals can be carriers of either the A1, A2 or A1/A2 allele. However, what has been proven is that individuals possessing the A1 allele of the ANKK1 gene have a significantly reduced number of dopamine receptors than individuals possessing the A2 allele, and this reduced number of dopamine receptors in carriers of the A1 allele has in previous research been associated with increased risk of risky alcohol use (Berggren et al, 2006; So Hee et al, 2013; Suraj Singh, Ghosh & Saraswathy, 2013; Wang, Simen, Arias, Lu & Zhang, 2013).
Interaction between ANKK1 Polymorphism and Risky Alcohol Use
receptors it has stood to reason that people possessing the A1 allele are more susceptible to risky alcohol use (Berggren et al, 2006; So Hee et al, 2013; Suraj Singh, Ghosh &
Saraswathy, 2013; Wang, Simen, Arias, Lu & Zhang, 2013). Studies have shown varying results, and the association remains controversial. Majority of studies though, have shown an association between the ANKK1 gene and Taq1A polymorphism with risky alcohol use. Berggren et al (2006) used a sample of Scandinavian participants consisting of 375 males and females, who all fulfilled the DSM-IV criteria for alcohol dependence rather than for risky alcohol use. They used 578 individuals as screened controls and 254 unscreened for alcohol consumption, so the total number of subjects were 1.217, one of the largest samples found about the ANKK1 gene. Their results showed that the genotype A1/A2 of the ANKK1 Taq1A polymorphism differed significantly between both the alcohol dependent group total and the screened and unscreened control groups. It also showed that the Taq1A A1 allele frequency was significantly overrepresented in the alcohol dependant subjects as compared to the control groups. The odds ratio for alcohol-dependency being associated with the A1 allele was 1.34, although its effect size was small. Consequently, the findings in this study lend further support to the notion of an association between the ANKK1 A1 allele and alcohol dependence.
One study, conducted by Singh, Ghosh and Saraswathy (2013) used a total of 129 participants who also met the DSM-IV criteria for alcohol dependency and 286 controls were also screened for four single-nucleotide polymorphisms, where Taq1A was one of them. The study results showed that minor A1 allele frequency of the TaqIA site was significantly higher among alcohol dependent subjects compared with controls, results that support the higher risk for alcohol dependency amongst carriers of the A1 allele. It also showed that individuals with the A1 allele have a significantly reduced number of DRD2 dopamine receptors than individuals carrying the A2 allele, which seems to be a part in what is causing the higher risk for alcohol dependency.
Another study by So Hee et al (2013) found similar results. They investigated the association between the ANKK1 Taq1A polymorphism and alcohol dependency in a Korean sample consisting of 245 participants who were all diagnosed using the DSM-IV criteria for alcohol dependency, and 110 healthy controls. Results showed a significant difference in genotype and allele frequency between the alcohol dependent group and the controls. Results also indicated that a haplotype −141C Del-G-A2 could play a protective role in alcohol dependency and that −141C Ins-A-A1 could have about 2.3 times higher risk of developing alcohol dependency. Their results leaned towards the same explanation as the previous study,
the reduced number of dopamine receptors increases the risk.
More recent studies, such as one carried out by Quraishi, Jain, Mishra & Ambekar (2017) show the same results. They looked at 79 male participants who all had sought treatment for their alcohol dependency and measured the amount of alcohol they consumed per day. Carriers of the A1 and A2 allele of the ANKK1 gene were compared with key demographics and alcohol dependence profile. Carriers of the A1 allele reported a significantly higher amount of alcohol consumed per day, and regression analysis also
showed that the carriers of the A1 allele were 2.5 times more likely to report a higher amount of alcohol consumption than carriers of the A2 allele.
A meta-analysis was conducted with the aim to examine the associations between the ANKK1 gene and alcohol dependency, in hopes of either confirming or denying what
previous research has stated (Wang, Simen, Arias, Lu, and Zhang, 2013). They examined the association between the ANKK1 Taq1A polymorphism and alcohol dependency in over 18 000 subjects and 61 case-control studies. They used both allelic and genotypic analysis, of which allelic association studies are based on comparing allele frequencies. There were 56 studies included in the allelic analysis, and the results confirm previous studies conclusions. There is an association between the ANKK1 Taq1A polymorphism and alcohol dependency, and that the risk for alcohol dependency seems to be strongest amongst carriers of the A1 allele.
Little research has been made regarding the ANKK1 gene in the theoretical frameworks of the “differential susceptibility hypothesis” and the “biological-sensitivity-to-context thesis,” (Belsky & Pluess, 2009; Boyce & Ellis, 2005) since these two theories are relatively new and have a unique outlook on susceptibility genes. Both theories claim that individuals who are carriers of susceptibility genes are not just more susceptible to negative
environments and risks, but also to positive environments. However, Brody, Chen & Beach (2013) examined the ANKK1 gene in relation to the “differential susceptibility hypothesis” with alcohol abuse as the outcome variable, and with prevention programs as the positive environmental factor. Using two longitudinal studies they identified individuals who were carriers of suspected risk alleles, amongst them those who were carriers of the A1 allele of the ANKK1 gene, and randomized them into two groups. One group of individuals who carried risk alleles and who did not get included in any alcohol prevention program, and one group with risk alleles that were included in the prevention program. They also used healthy control groups, meaning individuals that were not carriers of any risk alleles. The participants were studied for two years regarding their alcohol consumption, and results showed that
carriers of risk alleles, amongst them the A1 allele, that went through the prevention program had significantly lower alcohol consumption than the risk group that did not go through any prevention program. Their results seemed to indicate that the ANKK1 gene might be a susceptibility gene.
In sum, even though previous research has been controversial, most of the research seems to indicate that the ANKK1 gene, and specifically the A1 allele, increases the risk for risky alcohol use in carriers. The author of the present study found very little previous research that looked at the ANKK1 gene in the theoretical frameworks of the “differential-susceptibility hypothesis” and the “biological-sensitivity- to-context thesis” (Belsky & Pluess, 2009; Boyce & Ellis, 2005). Thus, the present study aims to examine whether the ANKK1 gene is a susceptibility gene and has the potential to both increase and decrease the risk of risky alcohol use when in interaction with negative and positive environmental factors. Parent-Child Relationship and Victimization
The “differential-susceptibility hypothesis” and the “biological-sensitivity- to-context thesis” (Belsky & Pluess, 2009; Boyce & Ellis, 2005) posit that individuals with susceptibility genes (such as the ANKK1 gene) will be more vulnerable in both a positive and adverse
environment. Meaning that they will flourish in a positive environment, and wither in an adverse environment. Many different factors have been used when studying the ANKK1 gene, but victimization and parent-child relationship has to the authors knowledge never been studied in relation to the ANKK1 gene. However, both victimization and parent-child
relationship have in previous studies been connected to increasing and decreasing the risk of alcoholism (Branstetter, Furman & Cottrell, 2009; Branstetter & Furman, 2013; Mak & Iacovou, 2019; Miller, Downs & Testa, 1993; Marschall-Lévesque et al, 2017; Nayak, Lown, Bond & Greenfield, 2012) .
Studies that have focused on sexual or physical victimization (Marschall-Lévesque et al, 2017; Miller, Downs & Testa, 1993; Nayak, Lown, Bond & Greenfield, 2012) with both men and women in their sample have found that victimization do play a part in increasing the risk of risky alcohol use. Victimization in childhood, adolescence or just at any point or several points during the life course increases the risk of becoming alcoholic. Usually alcohol has shown to be consumed as a form of self-medication.
Parent-child relationship, on the other hand, has the potential to be a protective factor (Branstetter, Furman & Cottrell, 2009; Branstetter & Furman, 2013; Mak & Iacovou, 2019). A warm relationship, but also the quality of or perceived good relationship with one’s parents, has shown in several studies to decrease the risk of hazardous substance use in
adolescence. However, it is unclear for how long a period it continues to be a protective factor, or if the risks increase if the relationship changes later in life. Compared to controls, a presently good parent-child relationship helps to diminish the risk of unhealthy drinking or other substance use.
Victimization can have a negative effect on risky alcohol use and parent-child relationship a positive one, the question that remains to be disentangled is whether these factors interact with the ANKK1 gene in increasing and decreasing the risk of risky alcohol use.
As mentioned earlier, there are two modern theories that focus on susceptibility genes and gene X environment interaction, and those are the “differential-susceptibility hypothesis” (Belsky & Pluess, 2009) and the “biological-sensitivity- to-context thesis” (Boyce & Ellis, 2005). The central difference between these two theories is what role they assign to the importance of nature vs nurture. Whereas the “differential susceptibility hypothesis” has its focus on nature without excluding the role of nurture, and the “biological-sensitivity-to-context thesis” has its focus on nurture without disregarding the influence of nature. What they both predict, however, is that some individuals will be more susceptible to both negative and positive life events. Meaning that while these individuals might suffer more from adverse events compared to others, they will also benefit more from positive experiences than other individuals would. In other words, they can become exceptional individuals with a good upbringing and lack of adversity and succeed in life at a higher rate than others, but in an adverse environment they will have a harder time making it through life than other people with the same life circumstances. When previous research has talked about susceptibility genes, it has been only in relation to negative outcomes (US National Library of Medicine, 2020). But these two theories mean that a susceptibility gene is more sensitive to not only adverse environments, but also to positive once (Belsky & Pluess, 2009; Boyce & Ellis, 2005) The ANKK1 gene has the potential to be a susceptibility gene (Koeneke et al, 2020; Ponce et al, 2009) and victimization and positive parent-child relationship will be the test for negative and positive life experiences.
These two theories also claim to have their roots in evolutionary theory. The “differential susceptibility hypothesis” with its main focus on nature claims that children should vary in their susceptibility to child rearing, and that modern biology means that natural selection shapes things not just to survive but also to reproduce, it is the ultimate biological imperative (Belsky & Pluess, 2009). There are mainly two different ways of
reproduction, such as when you get immediate descendants like children and grandchildren, but also when your sister, nice, brother and nephew reproduce and passes on a part of your genetic make-up to a next generation. As parents never could know, in the past or now in the present, which child rearing practices would prove most effective for them to increase their chances of both immediate and second-hand reproduction, it benefited them to have children who varied in their developmental plasticity. So, if a way of parenting proved dysfunctional and possibly could worsen their chances of immediate reproduction, it would be in the favour of evolution to have one or more children that are more resilient to the effect of child rearing, who are less malleable to any negative effect. It would also benefit their more malleable siblings insofar as second-hand reproduction goes. If a form of child rearing proved positive and good, this would affect the malleable children, those who have a higher developmental plasticity, to a greater extent than the resilient siblings and their reproduction chances would be higher than those of the other siblings even though they both were raised in positive ways. To summarize, it is adaptive to have a child varying in plasticity, and it is adaptive for them to have siblings with contrasting abilities.
The “biological sensitivity to context” theory has a very similar, but still slightly different, evolutionary approach (Boyce & Ellis, 2005). The theory posits that children in an especially supportive or unsupportive environment should develop or maintain high levels of physiological stress reactivity, which is what they regard as a susceptibility factor/plasticity mechanism. They expect high reactivity to emerge both in highly protected social
environments and in highly stressful ones. For those children who are raised in supportive contexts it would be adaptive to be maximally influenced by that positive developmental environment. This positive environment should enhance the social competitiveness of the child and help it develop a wide range of competences, and therefore increase the
reproductive chances and make them more attractive to a potential partner. Just as those growing up in more harsh conditions could increase their chances of attracting mates by becoming vigilant and capable of combating any risks that might come their way. Thus, the hypothesis is that their stress response reactivity is a conditional adaptation, made to enable individuals to early in life fit into their conditions and make them attractive as a partner choice. So, weather plasticity is considered a central function of either nature, nurture or their interaction the claim of individual differences in plasticity is central to both evolutionary arguments.
In sum, both the ”differential-susceptibility hypothesis” (Belsky & Pluess, 2009) and the “biological-sensitivity- to-context thesis” (Boyce & Ellis, 2005) are based on evolutionary
theory, and there are modern studies that have shown results supportive of their susceptibility thesis (Lorber, Erlanger & Slep, 2013; Obradović, Bush, Stamperdahl, Adler & Boyce, 2010; Tuvblad et al, 2016). Both theories are very similar, but there are some key differences between them, and they build of each other. Therefore, the author of the present study considers them both to contribute to the present thesis. However, considering the relative newness of these theories and the fact that studies that have included or tested them are somewhat scarce, there is a gap in the literature which the current study attempts to fill. Knowledge Gap
Studies surrounding the ANKK1 gene and its association with risky alcohol use are controversial because of the varied results, and it is not until recently that the Taq1A
polymorphism who has been rather widely researched were found to lay in the ANKK1 gene, which of course could have played a part in confusing some of the previous research.
However, the author of the present study found very few studies that have applied the
“differential-susceptibility hypothesis” and the “biological-sensitivity- to-context thesis” into their research surrounding the ANKK1 gene. These two theories are relatively new and different because of the way that they look at both positive and negative environmental factors and an individual’s susceptibility. Thus, few studies have included this approach, the focus has rather been negative factors and their influences. Additionally, it has never been investigated with victimization and parent-child relationship as interacting factors. A lot remains to be understood regarding this gene and its association with risky alcohol use and its role as a possible susceptibility gene, and hopefully this study will in part help fill the current knowledge gap.
Aim of the study and hypothesis
The aim of the present study was to examine the association of risky alcohol use with (1) ANKK1 gene, and (2) two-way interactions of the ANKK1 gene with parent-child
relationship and victimization. Based on theory, i.e. “differential-susceptibility hypothesis” (Belsky and Pluess, 2009) and the “biological-sensitivity- to-context thesis” (Boyce and Ellis, 2005) the following hypotheses were formulated. (A) Individuals with the ANKK1 gene carrying the A1 allele and who have been repeatedly or severely victimized during their lifetime will be more prone to express risky alcohol use than individuals that are not carriers of the A1 allele. (B) Individuals who are carriers of the A1 allele who report to have a good relationship with their parents will show a reduced risk of risky alcohol use.
The current study used data from a large Swedish population-based, cross-sectional and retrospective project called RESUME and all analyses in this study were conducted using the statistical software IBM SPSS Statistics Version 0.26 (IBM Corp, 2009). The next sections will describe details of the participants, measurements used in the present study, procedure, ethics and the analyses used to answer the aim of the present study.
Participants for the present study were taken from the Retrospective Study of Young People's Experiences (RESUME). RESUME is Swedish-based, retrospective and cross-sectional and examines the association of stressful and adverse events in childhood and adolescence (Cater, Andershed & Andershed, 2014; Tuvblad et al., 2016). It also measured different outcomes of these experiences, such as aggressive behavior, criminal behavior, addictions to alcohol and/or other drugs, social adjustment as well as mental and physical health. The sample in RESUME consists of 2.500 randomly selected individuals, but the number of participants in the present study is less than the 2.500. Because a DNA sample was necessary to be included in the present study only participants who contributed a saliva sample were included. That left the current study sample at 1.800 participants, resulting in 845 males (47%) and 955 females (53%) who were born between 1987 and 1991. This placed them at the ages of 20 to 24 years old at the start of the study (with a mean age = 22.15 years). The individuals in the RESUME project were recruited from a national population register at Statistics Sweden, and in order to examine whether the participants differed significantly from those who declined or were never reached a comparison was made between them and 30 randomly selected
individuals. No significant differences between the two groups on key demographics or outcomes were found, with the exception being that only participants in RESUME reported having “been forced to participate in sexual activities.”
The data were collected between March and December in 2011 (Cater, Andershed & Andershed, 2014; Tuvblad et al., 2016). The study included both an interview section at the beginning and end with a survey in between. Trained interviewers administered the protocol, which also included informed consent and DNA saliva samples outside of the face to face interviews and questionnaire. In the present study only data collected via the questionnaire and DNA samples were included.
Risky Alcohol Use. Alcohol use was measured using a part of the Alcohol Use Disorders Identification Test (AUDIT), an instrument for identification of hazardous and
harmful alcohol consumption. AUDIT consists of a 10-item scale, but only three of the items were used to measure alcohol consumption in the present study. This was because a very low percentage of the participants showed any indication for alcohol abuse or dependency when checking the results of all the 10 items in the scale, while there were a considerably larger number that showed a risky alcohol use. The three questions included in the index were the first three questions in AUDIT, the three questions that are said to capture participants that just show a risky alcohol use (Wennberg, Källmén, Hermansson & Bergman, 2008). The first question asks “how often do you drink alcohol,” with five possible responses ranging from “never,” “once a month or less,” “2-4 times a month,” “2-3 times a week,” and “4 times a week or more.” The second question then asks “how many glasses do you drink on a typical day when you are drinking alcohol” (and also gives examples of which type of drink and its percentage, such as whisky, wine or beer) and also have five possible responses ranging from “1-2 glasses,” “3-4 glasses,” “5-6 glasses,” “7-9 glasses” and “10 or more glasses.” And the last questions asks, “how often do you drink six such glasses or more at the same occasion?” with five possible responses ranging between “never,” “less than once a month,” “every month,” “every week” and “daily or almost daily.” A higher score in the index indicated a risky alcohol consumption, and the scores ranged between 1 and 15. A participant was considered having a risky alcohol use if they scored 10 or higher in the index. The index had a Cronbach’s alpha of 0.66 which is considered a decent internal consistency, but not good. However, considering that these three questions are meant to be a part of a 10-item
measurement battery, it is to be expected that only the three of them together will show a weaker internal consistency.
Parent-Child Relationship. Parent-child relationship was measured using two items: “How would you describe your relationship with your mother?” and “How would you
describe your relationship with your father?” There were four possible responses, ranging from “very close” to “not very close at all.” The variable was recoded into three categories “Not close,” “Pretty close” and “Very close”. Cronbach’s Alpha for the two items were low, at .51, which is not unexpected given that the two questions were nearly identical.
Victimization. The type of victimization that was included in the present study was physical (e.g., physically having been forced to do something you did not want to do, or having been hit, attacked with an object or by a group of people to name a few) and sexual victimization (e.g., been forced to touch somebody else’s genitalia, been raped, or filmed during sexual activities against once will to name a few). As the long-lasting impact of these types of victimization are the most researched (Marschall-Lévesque et al, 2017; Miller,
Downs & Testa, 1993; Nayak, Lown, Bond & Greenfield, 2012). There were eleven items used to measure some types of physical violence, and six of these came from the Juvenile Victimization Questionnaire (JVQ), except that they were modified to cover lifetime
victimization and different perpetrators (JVQ; Finkelhor, Hamby, Ormrod, & Turner, 2005; Hamby, Finkelhor, Ormrod, & Turner, 2004). The additional five items were added in order to fully cover up other types of physical victimization that have been examined in other studies (Janson, Långberg, & Svensson, 2007; May-Chahal & Cawson, 2005). There were seven items that measured sexual victimization, five of them were taken from JVQ and modified (Finkelhor et al, 2005; Hamby et al, 2004) and the remaining two items were taken from the NSPCC study (May-Chahal & Cawson, 2005).
All of the questions were asked on the same 6-point response scale that ranged from “zero times”, “one time”, “two times”, “three times”, “four times” and “five times or more”. The questions were also framed to ask if the participant ever had experienced that type of victimization during their lifetime (Cater, Andershed & Andershed, 2014). The index consisted of these 18 items and was then recoded into a dichotomous variable, where every participant that had never been victimized was placed in a “Never” category and everyone that had been severely victimized one time or more placed in the “Once or more” category. The index had a Cronbach’s Alpha of 0.86 which indicates a high internal consistency. Procedure
Recruitment for the RESUME study was done over the phone, were the randomly selected participants were given information about the study (Cater, Andershed & Andershed, 2014; Tuvblad et al., 2016). Participants then received information over email and could also decide where they wanted the interview to take place. These face-to-face interviews were then carried out between March and December in 2011. Informed consent was collected from each participant before the start of the interview. In addition, any questions that were considered sensitive were answered by the participants either through pen and paper or an iPad
depending on which one the participant preferred. On average, the interviews and questionnaire took about an hour and the participants received 400 SEK for their participation. The study was also evaluated and approved by an ethics committee (#2010/463).
This study followed the Swedish scientific councils (Vetenskapsrådet) demands regarding ethical principles. There are four basic demands, which include the information demand (i.e., informationskravet) (1) meaning that all the participants were informed about the aim of the
study, their part in the study and everything that could possibly affect their willingness to participate and the terms regarding their participation (Vetenskapsrådet, 2002). This did of course include information about the fact that they can leave and interrupt their participation in the study at any given point in time, and should they choose to do so all information that has been gathered from them shall be destroyed. The second one is the demand of informed consent (i.e., samtyckeskravet) (2) meaning that the participants received information about the study and gave their consent to participate; this information was given both verbally and in writing and consent was also collected. The third demand is the one of confidentiality (i.e., konfidentialitetskravet) (3) this means that all information that is collected about the
participants are given the utmost confidentiality and is protected to the extent that
unauthorized individuals cannot gain access to it. In the case of the present study that meant the removal of any information that can identify the individual, such as names, numbers, email and address.
All current data used in the present study are kept on a computer that is password protected. In addition, a contract was signed between the author of the present study, Dr. Catherine Tuvblad who is the author’s advisor and Dr. Henrik Andershed who is the principal investigator (PI) of the RESUME study. All information will also be deleted from the authors computer after the finalization of the present study and no details of the study will be shown or shared with an unauthorized individual.
The fourth demand of the Swedish Research Council is that of utilization (i.e., nyttjandekravet) (4) which means that the collected data will not be used for any other purpose than scientific research and that collected information about the participants cannot be used against them for any form of decision that affects the individual (e.g. forced intake or other medical care) (Vetenskapsrådet, 2002). The study also follows the directions of the General Data Protection Regulation (Datainspektionen, n.d.) by not saving any personal, identifying information about the participants and with the study not being shared with unauthorized individuals, just as the data is password protected and will be deleted after the present study is finalized.
The DNA from RESUME was extracted from 200 ml of saliva and was collected with the Orange self-collection kit (DNA Genotek1) by using the silica-based Klear-gene DNA extraction method (Tuvblad et al, 2016). The Kiboscience Allele-specific Polymorphism assay (KASP) was used for genotyping analyses of single SNPs and was based on competitive allele-specific PCR and b-allelic scoring of the single SNPs. In order to be
capable of detecting contamination or non-specific amplification No-template control samples were included. The ANKK1 gene was investigated with its A1, A2 and A1/A2 alleles. A saliva sample was provided by 1,870 of the participants in RESUME, and ANKK1 genotype data were available for 1,800 of the participants.
All analysis was performed using the statistical software program IBM SPSS Statistics version 26.0 (IBM Corp, 2019). The analysis used to answer the study aim was a Two-Way Between-Groups Analysis of Variance (ANOVA). The dependent variable was Risky Alcohol Use, and the independent variables were Parent-Child Relationship, Victimization and the ANKK1 gene. A two-way between groups ANOVA was preferred because the author of the present study wished to investigate the interaction and main effects of one dependent variable and three independent variables. Main effects for Parent-Child Relationship,
Victimization and the ANKK1 gene were examined, as well as potential interaction effects of ANKK1*Victimization and ANKK1*Parent-Child Relationship. A between groups ANOVA was needed because of the three groups of individuals that the author of the present study was interested in, meaning the three different alleles an individual can carry. Every individual possesses the ANKK1 gene, but they can be carriers of different alleles (Koeneke et al, 2020). These alleles have in previous research proven to have different effects on alcohol use (Berggren et al, 2006; So Hee et al, 2013; Suraj Singh, Ghosh & Saraswathy, 2013; Wang, Simen, Arias, Lu & Zhang, 2013). This means that one group of people are carriers of the A1 allele, another group the A2 allele and a third group of the A1/A2 allele (Koeneke et al, 2020). It was the differences between these three groups and their interaction with the other variables that was of interest for the present study.
Descriptive statistics were first run, checking for outliers and normal distribution for all the variables. The ANKK1 and Alcohol Use variables were normally distributed, but
Victimization and Parent-Child Relationship were not normally distributed, instead they had very high skewness and kurtosis values. When the variables were dichotomized and
categorized, normal distributions were achieved. The dependent Risky Alcohol Use variable was continuous, while Parent-Child Relationship and the ANKK1 gene were categorical (divided into three categories) and Victimization was dichotomous.
Before running the main analysis all assumptions for an ANOVA were tested (Tabachnick & Fidell, 2013). The included variables were one continuous dependent
variable, and two categorical and one dichotomous independent variable. All variables had an approximate normal distribution and no outliers were detected, meeting the normality test.
Homogeneity of variances were tested using, Levene’s test, the results were not significant which means we do not reject the null hypothesis of equal population variances and that the assumption of homogeneity of variances is met. Both main and interaction effects were examined, using Bonferroni correction and Tukey HSD as the post-hoc test that were run for both ANOVAS.
First, descriptive statistics were conducted on all variables to check for internal loss between the variables and to check the distribution between the two genders. A larger proportion of the females (75%) reported having been sexually or physically victimized compared to men (48%). Regarding Risky Alcohol Use, men showed a higher percentage at 43% compared to females at 16%. There was barley no gender difference between men and women on Parent-Child Relationship. The results also showed that both males and females more frequently were carriers of the A1/A2 allele compared to the A1 or A2 alleles, Table 1.
Table 1. Descriptive Statistics
ANKK1 alleles Total N = 1800 n (%) Females N = 955 n (%) Males N = 845 n (%) A2 359 (20%) 185 (14.1%) 174 (15%) A1/A2 917 (51%) 504 (38.4%) 413 (35%) A1 524 (29%) 266 (20.2%) 258 (22%)
Number of participants that have reported being severely sexually or physically victimized once
1119 (62%) 717 (75%) 402 (48%)
Number of participants who reported having a good parent-child relationship
1065 (59%) 559 (59%) 506 (60%)
Number of participants who reported risky alcohol use
516 (29%) 156 (16%) 360 (43%)
A two-way between-groups analysis of variance was conducted next to explore the impact of the ANKK1 gene and Parent-Child Relationship on Risky Alcohol Use. Participants were divided in three groups based on which allele they were carriers of from the ANKK1 gene, the A1 allele, A2 allele and the A1/A2 allele.
Figure 1 shows that the risk for Risky Alcohol Use increased for carriers of all alleles when they had been victimized one time or more. The risk seemed to be highest for carriers of the A2 allele, and almost as much for carriers of the A1 allele. Carriers of the A1/A2 allele had a higher risk of Risky Alcohol Use compared to carriers of the other two alleles without ever having been victimized, but their risk also increased the least when Victimization became a factor, Figure 1.
Figure 1. Relationship between Alcohol Use, Victimization and the Different Alleles of the ANKK1 Gene.
Note. Y axis = Reported Risky Alcohol Use; X axis = Reported Victimization; Separate lines = Three different groups as separated by which allele they carry.
When looking at Figure 2 an unexpected pattern emerged. The risk of Risky Alcohol Use remained approximately the same for carriers of the A1 allele despite their relationship with their parents. Nevertheless, for carriers of the A2 and A1/A2 allele, the risk for risky alcohol use seemed to be highest when their relationship to their parents were described as “pretty close.” The risk decreased somewhat if they had a “very close” relationship to their parents. The risk seemed to be at the lowest for all carriers when they had reported that their
Figure 2. Relationship between Alcohol Use, Parent-Child Relationship and the Different Alleles of the ANKK1 Gene.
Note. Y axis = Reported Risky Alcohol Use; X axis = Reported Parent-Child Relationship; Separate lines = Three different groups as separated by which allele they carry.
Lastly, main and interaction effects of ANKK1 and Parent-Child Relationship on Risky Alcohol Use were examined using a two-way between group ANOVA. The interaction effect between ANKK1 and Parent-Child Relationship was not statistically significant, F (4.1548) = 1.432, p = .221 and the partial eta squared was very small, at .004. The test did not show a statistically significant main effect for ANKK1, F (2.1548) = .023, p = .977 on Risky Alcohol Use and it had a very small partial eta squared at .000. The test did show a
statistically significant main effect for Parent-Child Relationship F (2.1548) = 6.020, p = .002 on Risky Alcohol Use, with a small partial eta squared at .008, Table 2.
Post Hoc comparisons on Parent-Child Relationship were run using Tukey HSD test. Results indicated that the mean score for “Not close at all” (M = 7.50, SD =1.85) was
significantly different from “Pretty close” (M =8.07, SD = 2.04) and “Very close” (M = 7.93, SD =2.02). No statistically significant difference was found between “Pretty close” (M = 8.07, SD = 2.04), and “Very close” (M = 7.93, SD = 2.02). Meaning that a “Not close at all” Parent-Child Relationship do have an impact on Risky Alcohol Use, while a “Pretty close”
and “Very close” Parent-Child Relationship do not have a statistically significant impact on Risky Alcohol Use.
Table 2. Main and Interaction Effects of ANKKI and Parent-Child Relationship on Alcohol Use
Predictors Sum of squares
F Sig. Partial Eta
Squared Intercept 59977.054 1 59977.054 14816.117 .000 .905 ANKK1 .188 2 .094 .023 .977 .000 Parent-child relationship 48.742 2 24.371 6.020 .002** .008 ANKK1*Parent-child relationship 23.182 4 5.795 1.432 .221 .004 Error 6266.452 1548 4.048
Note. Difference between groups p < .05, shown through Tukeys post hoc-test. *** p < 0.001; ** p < 0.01; * p < 0.05
A second two-way between-groups analysis of variance was then conducted to explore the impact of ANKKI and Victimization on Risky Alcohol Use in order to examine potential main and interaction effects. No statistically significant interaction effect was found between ANKK1 and Victimization, F (2.1633) = 1.451, p = .235 with a very small partial eta squared at .002. There was a statistically significant main effect for Victimization, F (1.1633) = 26. 498, p = .000 though the partial eta squared was small at .016, meaning that Victimization explains a small but statistically significant part of the variance in Risky Alcohol Use. Since Victimization is dichotomous, no Post Hoc results will be presented for this variable. The only statistically significant results were the main effect of Victimization and Parent-Child Relationship on Risky Alcohol Use. Even though the results presented in Figure 1, seemed to indicate a tendency towards different outcomes for carriers of different alleles, these results were not statistically significant. The ANKK1 gene does not have a significant impact on Risky Alcohol Use on its own or in interaction with Parent-Child Relationship or Victimization. Only Victimization and Parent-Child Relationship explained a small part of the variance in Risky Alcohol Use.
Table 3. Main and Interaction Effects of ANKK1 and Victimization on Alcohol Use Predictors Sum of
F Sig. Partial Eta Squared Intercept 80959. 193 1 80959. 193 20062. 457 .000 .925 Victimization 106.929 1 106.929 26.498 .000 .016*** ANKK1 1.688 2 .844 .209 .811 .000 ANKK1*Victimization 11.712 2 5.856 1.451 .235 .002 Error 6589.739 1633 4.035
Note. Difference between groups p < .05, shown through Tukeys post hoc-test. *** p < 0.001; ** p <0.01; * p < 0.05
The aim of the present study was to examine the associations of risky alcohol use with (1) the ANKK1 gene, and (2) two-way interactions of the ANKK1 gene with parent-child
relationship and victimization. Results showed no statistically significant interaction effect between victimization and the ANKK1 gene, nor between parent-child relationship and the ANKK1 gene. The ANKK1 gene did not show any significant main effect either. However, results did indicate a small but statistically significant main effect for both victimization and parent-child relationship. There was a modest indication that carriers of all alleles of the ANKK1 gene had a higher risk of risky alcohol use when they had been victimized, whereas carriers of the A2 allele seemed to have the highest increased risk, but carriers of the A1 allele had an increase that was almost as high. Carriers of the A1/A2 allele had a higher risk than the rest even though the carrier had not been exposed to victimization, and when
victimized the risk increased the least for those carriers. Figure 2 for parent-child relationship seemed to indicate that carriers of the A2 and A1/A2 allele consumed the least amount of alcohol when they reported having experienced a “not close” parent-child relationship. They consumed the most alcohol when the relationship was described as “pretty close,” only for the risky alcohol use to decrease slightly when the relationship was described as “very close.” Carriers of the A1 allele, however, barley showed any increased or decreased risk for risky alcohol use no matter what category of parent-child relationship they were in. A Post Hoc test was run on parent-child relationship and results showed that it was the “Not close at all” category that was significantly different from the other two categories. Since the ANKK1 gene did not show any significant main or interaction effect these results should not carry too
Findings in the Present Study in Relation to Previous Research
The statistically significant main effect for victimization is in line with previous research. Several studies (Marschall-Lévesque et al, 2017; Miller, Downs & Testa, 1993; Nayak, Lown, Bond & Greenfield, 2012) have shown that sever or repeated victimization increases the risk of risky alcohol use, and the results of this study seems to indicate the same.
However, the results depicted in Figure 1 in the present study, seemed to show that the risk was highest for carriers of the A2 allele, results that are not in line with previous studies or with the hypothesis of the present study. Previous research has rather strongly indicated that carriers of the A1 allele have a heightened risk for risky alcohol use (Berggren et al, 2006; So Hee et al, 2013; Suraj Singh, Ghosh & Saraswathy, 2013; Wang, Simen, Arias, Lu & Zhang, 2013). Results in the present study did not show any statistically significant relationship between the ANKK1 gene and risky alcohol use, or any interaction effect between the ANKK1 gene and victimization. Thus, the gene itself does not show any impact on risky alcohol use in the present study. The observed difference between carriers of the A2 and A1 allele was also small, meaning that the results might just be coincidental. Nonetheless, results from the present study do not indicate that the A1, A2 or A1/A2 alleles have any impact on the participants alcohol use because of the non-statistically significant results. It is possible that a different sample could have produced a different set of results. Previous research of the ANKK1 gene have used samples of participants that have been diagnosed with alcohol dependency syndrome and healthy control groups. Studies that have used a sample of more chronic alcoholics have often showed statistically significant results. Very few participants in the RESUME sample showed any indications of alcohol dependency, and in relation to the results this might indicate that for an association between the ANKK1 gene and alcohol use to occur the intake of alcohol has to be severe enough to be labelled alcohol dependency. Parent-child relationship also showed a statistically significant main effect in relation to risky alcohol use, though the results were not in line with previous research or the current studies hypothesis (Branstetter, Furman & Cottrell, 2009; Branstetter & Furman, 2013; Mak & Iacovou, 2019). Previous research has shown that a good parent-child relationship works as a protective factor against risky alcohol use, though it has been more unclear if a good relationship in adolescence continues to work as a protective factor even if the relationship changes later in life or if it is the current parent-child relationship that matters. Nevertheless, the results from this study showed that a good parent-child relationship did not work as protective factor. Figure 2 seemed to show that those who categorised their relationship as
“Not close at all” had the lowest risk of risky alcohol use, and that those who saw themselves as having a “Pretty close” relationship had the highest risk for risky alcohol use. The risk decreased for those who reported that their relationship was “Very close,” but their risk for risky alcohol use still remained higher than for those who reported that they were “Not close at all.” These results are not in line with previous studies or the current hypothesis, but the results could have been influenced by the way that parent-child relationship was measured in the present study. Only two variables were used, where the questions were the same for their relationship with their mother and father, respectively. One could argue that only two
variables that ask the same question are not enough to capture the true parent-child
relationship, and had more questions been asked and included in the index the results might have been different. Another hypothesis in the present study was that carriers of the A1 allele would be the most protected from having a risky alcohol use if they had a “very close” parent-child relationship, but the results indicated something different. It rather showed that carriers of the A1 allele were the least effected by the nature of the parent-child relationship; they barely showed any increased or decreased risk for risky alcohol use if the relationship was “very close,” “pretty close” or “not close at all.” Carriers of the A2 allele seemed to show the biggest decreases and increases in risk for risky alcohol use depending on the relationship, and carriers of the A1/A2 allele showed a pattern very similar to carriers of the A2 allele in risk depending on the nature of the parent-child relationship. However, since the ANKK1 gene did not show any statistically significant relationship to risky alcohol use or any interaction effect with parent-child relationship the results should be interpreted with caution. The Post Hoc test did show that it was the “Not close at all” categorization of the relationship that differed significantly from the rest, indicating that this type of parent-child relationship relates to the use of alcohol.
Findings in the Present Study in Relation to Theory
The current study used the” differential-susceptibility hypothesis” (Belsky & Pluess, 2009) and the “biological-sensitivity- to-context thesis” (Boyce & Ellis, 2005) as a theoretical framework. The ANKK1 gene is suspected of being a susceptibility gene (Koeneke et al, 2020; Ponce et al, 2009), which would mean that individuals who are carriers of a certain allele (in the case of the ANKK1 gene it would be the A1 allele) would be more susceptible to both negative and positive environmental factors. In the present study, the negative factor was victimization, and the positive factor parent-child relationship. The hypotheses for the present study was as follows; “(A) Individuals with the ANKK1 gene carrying the A1 allele and who have been repeatedly or severely victimized during their lifetime will be more prone
to express risky alcohol use than individuals that are not carriers of the A1 allele. (B)
Individuals who are carriers of the A1 allele who report to have a currently good relationship with their parents will show a reduced risk of risky alcohol use.” The results of the present study did not support any of the two hypotheses. Even though the results are almost in line with the first hypothesis, since both carriers of the A2 and the A1 allele showed the highest increase in risky alcohol use when they had been victimized once or more. However, the A2 allele showed a slightly higher risk than the A1 allele, which goes against previous research (Berggren et al, 2006; So Hee et al, 2013; Suraj Singh, Ghosh & Saraswathy, 2013; Wang, Simen, Arias, Lu & Zhang, 2013). Regarding the results from the parent-child relationship and risky alcohol use plot in Figure 2, they went straight against the second hypothesis. A good parent-child relationship was thought to work as a protective factor and decrease the risk for risky alcohol use in carriers of the A1 allele (Branstetter, Furman & Cottrell, 2009; Branstetter & Furman, 2013; Mak & Iacovou, 2019), instead it seemed to work in the opposite direction. Rather, parent-child relationship categorised as “not close at all”
decreased the risk of risky alcohol use in carriers of the A2 and A1/A2 alleles, while the risk was higher for those who had reported that they had a “very good” parent-child relationship, but the risk peaked highest for those who reported to have a “pretty close” relationship. While carriers of the A1 allele had no noticeable decrease or increase in their alcohol use in relation to parent-child relationship, it seemed that parent-child relationship had no major influence on their alcohol use. These results are somewhat odd, and as they go against previous research, indicating that they should be viewed with utmost caution. It is likely that the two items used, and the later categorisation of these variables, failed to capture the true parent-child relationship. All results regarding the ANKK1 gene were not-statistically significant, which needs to be considered when interpreting the results of the present study in relation to previous research and theory.
Strengths and Limitations
There are a few methodological limitations related to the present study. One of them is in the way that parent-child relationship was measured. It was measured in the form of two items (the questions simply asked them how they would rate their relationship to their mother and father respectively), and it can be criticised for whether two questions truly capture the nature of such a relationship. The problem was that all other questions regarding parent-child
relationship in RESUME were measured in different ways, including different response alternatives which made the index small with simply two questions that both measured the relationship in the same way. The other issue was the lack of participants in the study with
alcohol dependency problems. There were so few in the study that used alcohol or any other form of drug to a higher degree than what is normal, that any potential link between the different alleles in the gene and risky alcohol could have been too weak. If a different sample that consisted of individuals with more severe alcohol problems had been used, or if
individuals diagnosed with alcohol dependency had been compared with a healthy control group, the study might have seen different results more in line with previous research (Berggren et al, 2006; So Hee et al, 2013; Suraj Singh, Ghosh & Saraswathy, 2013; Wang, Simen, Arias, Lu & Zhang, 2013). There was also a rather large internal loss between the different variable groups, as not everyone chose to give a DNA sample, others had not responded to all the questions regarding victimization or alcohol use, and some had skipped the question surrounding parent-child relationship. This led to the number of participants being unequal between the variables in the study (Bryman & Nilsson, 2018). Another disadvantage was the need to transform some variables into categorical or dichotomous variables. It was a necessity for the analysis and in order to approximate a normal distribution, but some of the nuances in the data for parent-child relationship and victimization most likely got lost in the process.
The present study did also have some strengths. Something that is in clear favor of this study compared to other studies is that data on the ANKKI gene was collected from a large number of participants (Bryman & Nilsson, 2018). There were 1800 participants with the ANKK1 gene that could be included in the present analyses, where previous studies often only have included a few hundred participants (Berggren et al, 2006; So Hee et al, 2013; Suraj Singh, Ghosh & Saraswathy, 2013). Another strength is the use of validated
instruments such as AUDIT (Cassidy, Schmitz & Malla, 2008) and JVQ (Finkelhor et al, 2005) as well as their high internal consistency. This ensures that the questions truly capture what they intended to measure, which in this case is the participants actual alcohol use as well as their sexual and physical victimization. Another strength is the fact that a randomly selected sample of participants were included in RESUME, and the fact that 30 randomly selected individuals acted as a control group to examine if any characteristics differed between the sample and those who declined to participate (Bryman & Nilsson, 2018). This took away any possible selection bias.
Implications of the Current Study
The research into genes and their potential relationship to human addiction and behavior is relatively new, and any practical implications often takes the form of laying a foundation for future studies. However, implications of the current study seem to show that the ANKK1
gene does not play a part in increasing the risk for risky alcohol use, but that victimization does increase the risk for alcohol use, even when the participant only has one experience of having been physically or sexually victimized. This implies that all victims of sexual or physical abuse should be offered and given proper support and treatment. Both medically but also psychological care, such as seeing a therapist to decrease the risk of risky alcohol use. The results also imply that ANKK1 is not a susceptibility gene, but more research is needed before we can draw any firm conclusions regarding this gene. If we can identify individuals that are carriers of certain susceptibility genes or alleles, we can also target them for early prevention work. We could learn which positive environmental factors that counteract the negative factors and educate professionals in the field who deals with vulnerable individuals to learn to harness and strengthen these protective factors. Possibly to also find a medical solution to genetic “weaknesses”, and perhaps learn how to nullify them.
Future research should focus more on applying the” differential-susceptibility hypothesis” (Belsky & Pluess, 2009) and the “biological-sensitivity- to-context thesis” (Boyce & Ellis, 2005) in their research when examining the influence of genetics on human addictions and behaviors. When applying the” differential-susceptibility hypothesis” and the “biological-sensitivity- to-context thesis”, research should use victimization as a negative environmental factor, since results of the present study did show a statistically significant relationship between victimization and risky alcohol use. Parent-child relationship and its influence should also be examined further, but with a sample that consists more of diagnosed alcoholics and with an index consisting of more questions in hopes of truly capturing the parent-child relationship in a more nuanced way. The results should be different then what was found in the present study regarding the influence of the parent-child relationship. Future studies should not shy away from examining other potential positive and negative environmental factors that could influence the outcome. More research is also needed on the ANKK1 gene itself, since results so far remains controversial regarding its effect on alcohol use. Research is needed in order to determine whether the ANKK1 gene truly is a susceptibility gene or not. Future studies should also focus on making their sample sizes larger and mainly include individuals that are diagnosed with alcohol dependency since any connection between the gene and alcohol use might be too weak in a sample with participants that only show risky alcohol use.
In sum, this study shows that sexual or physical victimization, even when only experienced once, increases the risk of risky alcohol use. This study also indicated that the ANKK1 gene is not a susceptibility gene as well as stating that the different alleles has no statistically significant influence on an individual’s alcohol use. A bad parent-child relationship rather decreased the risk of risky alcohol use, but due to limitations in the study the results should be viewed with caution. No interaction effect between the ANKK1 gene, victimization or parent-child relationship could be found. Victims of sexual or physical abuse should be given proper medical and psychological care in order to prevent future risky alcohol use, and the ANKK1 gene needs to be further researched in order to establish if it does have any influence on alcohol use and whether it is a susceptibility gene. Future studies should include even larger sample sizes, as well as using participants that have been diagnosed with alcohol dependency when further examining the ANKK1 gene.
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