Predicting alcohol use from genome-wide polygenic scores, environmental factors, and their interactions in young adulthood

Abstract

<jats:title>Abstract</jats:title><jats:p>Alcohol use during emerging adulthood is associated with adverse life outcomes but its risk factors are not well known. Here, we predicted alcohol use in 3,153 adults aged 22 years from (a) genome-wide polygenic scores (GPS) based on genome-wide association studies for the target phenotypes number of drinks per week and Alcohol Use Disorders Identification Test (AUDIT) scores, (b) 30 environmental factors, and (c) their interactions (i.e. GxE effects). The GPS accounted for up to 1.9% of the variance in alcohol use (i.e. AUDIT-C score), while the 30 measures of environmental factors together accounted for 21.1%. The 30 GPS-environment interactions did not explain any additional variance and none of the interaction terms exceeded the significance threshold corrected for multiple testing. Our findings suggest that GPS and environmental factors have primarily direct, additive effects rather than interacting systematically.</jats:p><jats:sec><jats:title>Statement of Relevance</jats:title><jats:p>We consider our research to be of interest and significance to the wider public in addition to the academic community. A wide range of social, economic and health outcomes are attributed to alcohol use in emerging adulthood; however, its risk factors are not well known. Twin studies suggest that genetics account for about 40% of the difference in alcohol use between people. Identifying the environments that moderate the influence of individuals’ genetic predispositions on their alcohol use is key for developing and implementing effective interventions. In the current study, we show that individual-level genetic data and a wide range of environmental factors predict alcohol use in emerging adulthood. However, we did not find any evidence for the moderation of the individual’s genetic propensity for alcohol use by any of the environmental factors, suggesting that genes and the environment have additive effects rather than interacting systematically.</jats:p></jats:sec>

Gene-environment Interplay in Early Life Cognitive Development

“…Not finding significant GxE effects aligns with other studies that failed to detect meaningful moderations of genetic influences on phenotypic traits (e.g., Allegrini et al, 2020;Figlio et al, 2017;Kandaswamy et al, 2022;Plomin et al, 2022). This and other research suggest that identifying replicable GxE effects in the prediction of complex traits that are influenced by many genetic and environmental factors, like cognitive but also social-emotional development, may be impossible, at least with the methods that are currently available.…”

A genetically informed Registered Report on adverse childhood experiences and mental health

“…We derived polygenic scores for mental health problems; namely, major depressive disorder, anxiety disorder, bipolar disorder, autism, ADHD, antisocial behaviour, alcohol use disorder, and schizophrenia. We selected these polygenic scores because they (i) index genetic liability to a range of mental health problems, and (ii) have been found to be associated with ACEs [21][22][23]26 and/or psychopathology in young people [84][85][86][87] . We also derived negative control polygenic scores for traits with no known association with ACEs or mental health (namely, handedness and cataracts).…”