Having a spouse with higher PGSPAU was associated with higher AUDcrit and the social genetic effect of spousal PGSPAU was stronger among male target individuals, highlighting the potential importance of social genetic effects for understanding the pathways from genotype to alcohol use disorder.
Abstract
ABSTRACT Background The field's conventional understanding of how genetic factors impact risk for alcohol use disorder (AUD) typically focuses on direct genetic effects, or how an individual's own genetic predispositions are associated with the likelihood of experiencing clinically significant alcohol problems. More recently, studies of behavioral health outcomes in preclinical and human studies have demonstrated the potential importance of social genetic effects or the influence of a social partner's genotype on substance use and related outcomes. In this study, we sought to characterize social genetic effects for AUD, specifically in the context of marriage. Methods The sample included 660 opposite‐sex spousal dyads from the Collaborative Study on the Genetics of Alcoholism, restricted to individuals who were genetically similar to European reference panels. Measured and latent indicators of genetic risk included polygenic scores of problematic alcohol use (PGSPAU) and parental history of AUD (PHAUD), respectively. The outcome was Diaganostic and Statistical Manual (DSM)‐5 alcohol use disorder criterion count (AUDcrit) during marriage. Multilevel models accounted for the non‐independence of partners' data, including correlations between partners' genetic risk and residual covariance in AUDcrit. Results After accounting for direct genetic effects (i.e., the influence of one's own genetic predispositions) and the correlations between partners' genetic predispositions, we found that having a spouse with higher PGSPAU was associated with higher AUDcrit (B = 0.084, 95% CI [0.035, 0.132]). This social genetic effect was robust after adjusting for both partners' educational attainment. Spousal PHAUD was not associated with AUDcrit. Exploratory analyses indicated that the social genetic effect of spousal PGSPAU was stronger among male target individuals. Conclusions Findings highlight the potential importance of social genetic effects for understanding the pathways from genotype to alcohol use disorder and the need for further investigation of latent measures of genetic predispositions in studies of social genetic effects.
Abstract Background Genetic and environmental factors, and psychiatric traits, contribute to risk for alcohol use disorder (AUD) and other substance use disorders (SUDs) and traits. Weighing the importance of the different kinds of contribution to risk is important in understanding risk prediction – which may be important clinically -- and in formulating prevention and treatment strategies. Aims & Objectives We worked to quantify the contribution of environmental, psychiatric, and genetic factors to AUD across different ancestries. Although polygenic risk prediction represents an important future application, its utility may be enhanced when considered in the context of environmental predictors. We used deeply phenotyped African- and European-ancestry (AFR and EUR) samples to examine how genetic, psychiatric, and environmental factors predict AUD criterion count. Method We analyzed data from 11,021 individuals in the Yale-Penn Study sample, 5,843 AFR and 5,178 EUR. Polygenic risk scores (PRSs) were generated from genome-wide association studies (GWAS) of problematic alcohol use (PAU). Generalized linear regression and relative importance analyses determined the independent and interactive effects of environmental and genetic factors on AUD, considering criterion count rather than binary diagnosis to maximize power. Results PRSs for PAU were positively associated with AUD criterion count in both ancestries and predicted 1.9% of variance in AUD criterion count in the EUR sample and 1.3% in the AFR sample. A combination of education, substance use in the household before age 13, annual household income, and male sex explained 73.1% of the variance in AUD criterion count in the AFR sample and 58.9% in EUR. Among examined psychiatric disorders, posttraumatic stress disorder explained the most variance (10.0% in AFR, 9.4% in EUR), followed by anxiety disorders (3.4% in AFR, 6.2% in EUR) and major depressive disorder (1.3% in AFR, 2.1% in EUR). In the EUR sample, education level moderated the relationship between PRS for PAU and AUD criterion count. We completed similar analyses for several other SUDs, including opioid use disorder (OUD), which will also be discussed. Discussion & Conclusions In both AFR and EUR, environmental factors explained most of the variance in AUD criterion count, but polygenic risk was also a statistically significant predictor. The pattern of results for OUD was similar. These findings may help inform clinical, research, and policy efforts to mitigate AUD and OUD risk.
P. Na, J. Deak, D. Levey et al.· International Journal of Neu...· 0 citations
OBJECTIVE
Suicidal ideation (SI) and suicide attempt (SA) are both influenced by genetic, behavioral, and environmental factors. Alcohol use disorder (AUD) and adverse childhood experiences (ACEs) may mediate or moderate the effects of genetic liability for suicidality.
METHODS
Using data from 10,275 participants (43.8% female; 47.2% African-like genetic ancestry [AFR], 52.8% European-like genetic ancestry [EUR]), we tested whether polygenic scores (PGS) for SI and SA predicted lifetime suicidality outcomes. We evaluated whether AUD partially accounted for these associations and ACEs moderated the direct and indirect associations.
RESULTS
The SA PGS was significantly associated with SA (AFR: b = 0.36, SE = 0.01; EUR: b = 0.17, SE = 0.01; both ps < 2e-16), but the SI PGS was not associated with SI (p > 0.55). AUD statistically mediated the association between the SA PGS and SA, accounting for approximately 2% of the total association in AFR individuals and 10% in EUR individuals (both ps < 2e-16). Notably, the proportion of the association that was accounted for by AUD decreased as ACEs exposure increased, from 4.30% to 0.54% in AFR individuals and from 13.31% to 3.44% in EUR individuals. In contrast, there was only very modest mediation and no moderated mediation for SI.
CONCLUSIONS
Particularly among individuals with lower ACEs exposure, AUD accounted for a meaningful proportion of the association between genetic liability to SA and lifetime SA. These findings highlight different correlates across suicidality phenotypes and suggest potential clinical relevance for AUD in the association between genetic liability and SA.
V. Wu, X. Qin, A. Ashley-Koch et al.· Journal of Affective Disorde...· 0 citations
Research suggests that gene-environment correlation (rGE) is a central mechanism in the causation of depression. In particular, individuals with a higher genetic risk of depression also have a disproportionately high risk of experiencing adversities that may to some extent be attributed to one's own behaviors. However, the specific behaviors implicated in this process remain a black box. In this study, we leverage a real life social interactional setting to investigate the link between the genetic burden of depression and behaviors that may evoke negative evaluations from others. We analyze observations about survey participants made by interviewers who were not privy to participants' genetic risk. Analysis of approximately 18,000 unique participants across two US datasets of older adults shows that a higher polygenic index (PGI) of depressive symptoms increased the probability of being perceived as experiencing cognitive struggle and discomfort, and being unhealthy, but not of being seen as untrustworthy or disengaged. These effects seem to be accounted for by stable differences in average depressive symptoms between individuals rather than elevated depressive symptoms during particular interactions. Specific evaluations were to some degree explained by the genetic correlation of depression with certain other traits, including ADHD, neuroticism, and self-rated health. Our findings suggest that the process of rGE in depression involves micro behaviors that are interpreted by others as signals of low competence and that create awkwardness during social interactions.
Tamkinat Rauf, Jeremy Freese· Social Science & Medicine (1...· 0 citations
Gradients across socioeconomic status (SES) exist across most health conditions. While there has been significant attention devoted to the relationship between SES and physical and mental health, less research has examined how these relate to substance use disorders (SUD). In the current study, we use data from the prospective study within the Collaborative Study on the Genetics of Alcoholism (COGA) to explore the relationship between SES (in early life and adulthood) with multiple substance use disorders (alcohol, tobacco, cannabis, opioid, cocaine, and other substances). We find that early life SES (parental education and income) are associated with lower odds of lifetime diagnoses and lower severity for tobacco (TUD) and cannabis (CUD) use disorders. Associations with TUD remain after adjusting for demographic and familial risk, but associations with CUD were null after including familial risk factors. In participants aged 25+, adult education was associated with lower odds of diagnosis and severity for each of the SUD considered, conditional on early life SES, adult income, sociodemographic characteristics, and familial risk for SUD. Exploratory analyses of changes in SES revealed that those who were upwardly or downwardly mobile were at the lowest or greatest risk for more severe SUD across multiple substances, respectively. Our results demonstrate the relevance of both early life and adult SES in SUD risk. Early life conditions seem particularly relevant for specific substances while greater adult education was associated with reduced risk across all forms of SUDs.
P. Barr, I.-C. S. Kuo, M. Cooke et al.· medRxiv· 0 citations
These findings demonstrate the value of an artificial intelligence-driven literature review for informing comprehensive strategies to ad- dress the multifactorial nature of AUD.
Chenlan Wang, Kurtis Riener, LuoSan Yue· Proceedings of the Internati...· 0 citations
A body of research suggests that autistic individuals are less likely to drink alcohol than neurotypicals. However, emerging studies support a link between autism and alcohol use. This complex relationship is also reflected in studies that have examined the genetic overlap between the two traits. However, it is unclear whether there is a direct causal relationship between them. To explore this, we applied a combination of polygenic score and Mendelian randomisation analyses using publicly available genome-wide summary statistics and phenotypic measures of autism and alcohol consumption from UK Biobank. LD score regression analyses did not provide evidence of a genetic correlation between genetic liability for autism and drinks consumed per week (rg=-0.08; CI95%=-0.19, 0.03). Further, findings from polygenic score analyses did not support an association between genetic liability for autism and overall monthly alcohol intake. Univariable Mendelian randomisation analyses showed little evidence for a total effect of autism, attention deficit hyperactivity disorder (ADHD) or depression on overall monthly alcohol consumption. Multivariable Mendelian randomisation analyses also showed little evidence of a direct effect of autism on drinks per week when controlling for ADHD and depression. It is plausible that genetic liability for autism does not directly increase the amount of alcohol consumed but instead operates via commonly co-occurring difficulties in the autistic community. However, our findings may be due to methodological shortcomings, including weak instruments biasing effects towards to the null. Consequently, results should be interpreted with caution and further research conducted to address these issues.
S. Page, K. Easey, F. Sedgewick et al.· medRxiv· 0 citations
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