Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits.
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ABSTRACT:
SUBMITTER: Zhou H
PROVIDER: S-EPMC7485556 | biostudies-literature | 2020 Jul
REPOSITORIES: biostudies-literature
Publications
Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits.
Zhou Hang H Sealock Julia M JM Sanchez-Roige Sandra S Clarke Toni-Kim TK Levey Daniel F DF Cheng Zhongshan Z Li Boyang B Polimanti Renato R Kember Rachel L RL Smith Rachel Vickers RV Thygesen Johan H JH Morgan Marsha Y MY Atkinson Stephen R SR Thursz Mark R MR Nyegaard Mette M Nyegaard Mette M Mattheisen Manuel M Børglum Anders D AD Johnson Emma C EC Justice Amy C AC Palmer Abraham A AA McQuillin Andrew A Davis Lea K LK Edenberg Howard J HJ Agrawal Arpana A Kranzler Henry R HR Gelernter Joel J
Nature neuroscience 20200525 7
Problematic alcohol use (PAU) is a leading cause of death and disability worldwide. Although genome-wide association studies have identified PAU risk genes, the genetic architecture of this trait is not fully understood. We conducted a proxy-phenotype meta-analysis of PAU, combining alcohol use disorder and problematic drinking, in 435,563 European-ancestry individuals. We identified 29 independent risk variants, 19 of them novel. PAU was genetically correlated with 138 phenotypes, including sub ...[more]
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| S-EPMC7990311 | biostudies-literature
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Project description:(a) objectiveThis study aimed to identify trajectories of alcohol use (AU) and their associations with the development of alcohol use disorder (AUD) among young men with different weekly drinking patterns.(b) methodA longitudinal latent class analysis integrating several aspects of AU, such as drinking quantity and frequency on weekends vs workweek days, involving 4719 young Swiss men at ages 20, 21, and 25, and collected by the Cohort Study on Substance Use Risk Factors, was used to identify different AU trajectories over time. The development of AUD scores in these trajectories was investigated using generalized linear mixed models.(c) resultsSix AU trajectory classes, similar to those described in the literature, were identified: 'abstainers-light drinkers', 'light workweek increasers', 'light decreasers', 'moderate weekend decreasers', 'moderate workweek increasers', and 'heavy drinkers'. Only 12% of participants were assigned to a trajectory class with decreasing AU associated with a decline in their AUD score. AUD scores increased in trajectory classes exhibiting increasing AU on workweek days, despite low and moderate general AU. Finally, more than 59% of participants were on an AU trajectory presenting no change in their mean AUD score over time.(d) conclusionsMaturing out of problematic AU in emerging adulthood is not the norm in Switzerland, and the AUD score developed in late adolescence remains until at least emerging adulthood. AU on workweek days is a more practical marker of potentially problematic AU. This calls for timely interventions in adolescence and concerning regular drinking on workweek days in emerging adulthood.
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Project description:The link between autonomic stress reactivity and subjective urge/craving has been less systematically examined in behavioral addictions (i.e. problematic Internet use) than in substance use disorders. The present study investigated whether problematic Internet users (PU) show enhanced autonomic stress reactivity than non-PU, indexed by lower Heart Rate Variability (HRV) and higher Skin Conductance Level (SCL) reactivity during the Trier Social Stress Test (TSST), whether greater reactivity is related to stronger Internet craving, and whether problematic Internet usage is associated with some dysfunctional psychological features. Based on their Internet Addiction Test scores, participants were divided into PU (N = 24) and non-PU (N = 21). Their heart rate and skin conductance were continuously recorded during baseline, social stressors, and recovery. Craving for Internet usage were collected using a Likert scale before and after the TSST. The SDNN, an overall measure of HRV, was significantly lower in PU than non-PU during baseline, but not during and after stressful task. Furthermore, only among PU a significant negative correlation emerged between SDNN during recovery and craving ratings after the test. No group differences emerged for SCL. Lastly, PU endorsed more mood, obsessive-compulsive, and alcohol-related problems. Our findings suggest that problems in controlling one's use of the Internet may be related to reduced autonomic balance at rest. Moreover, our results provide new insights into the characterization of craving in PIU, indicating the existence of a relationship between craving for Internet usage and reduced autonomic flexibility.
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Project description:Peer behaviour plays an important role in the development of social adjustment, though little is known about its genetic architecture. We conducted a twin study combined with a genome-wide complex trait analysis (GCTA) and a genome-wide screen to characterise genetic influences on problematic peer behaviour during childhood and adolescence. This included a series of longitudinal measures (parent-reported Strengths-and-Difficulties Questionnaire) from a UK population-based birth-cohort (ALSPAC, 4-17 years), and a UK twin sample (TEDS, 4-11 years). Longitudinal twin analysis (TEDS; N ≤ 7,366 twin pairs) showed that peer problems in childhood are heritable (4-11 years, 0.60 < twin-h(2) ≤ 0.71) but genetically heterogeneous from age to age (4-11 years, twin-r(g) = 0.30). GCTA (ALSPAC: N ≤ 5,608, TEDS: N ≤ 2,691) provided furthermore little support for the contribution of measured common genetic variants during childhood (4-12 years, 0.02 < GCTA-h(2)(Meta) ≤ 0.11) though these influences become stronger in adolescence (13-17 years, 0.14 < GCTA-h (2)(ALSPAC) ≤ 0.27). A subsequent cross-sectional genome-wide screen in ALSPAC (N ≤ 6,000) focussed on peer problems with the highest GCTA-heritability (10, 13 and 17 years, 0.0002 < GCTA-P ≤ 0.03). Single variant signals (P ≤ 10(-5)) were followed up in TEDS (N ≤ 2835, 9 and 11 years) and, in search for autism quantitative trait loci, explored within two autism samples (AGRE: N Pedigrees = 793; ACC: N Cases = 1,453/N Controls = 7,070). There was, however, no evidence for association in TEDS and little evidence for an overlap with the autistic continuum. In summary, our findings suggest that problematic peer relationships are heritable but genetically complex and heterogeneous from age to age, with an increase in common measurable genetic variation during adolescence.
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