Genome‐wide association study of alcohol use disorder identification test (AUDIT) scores in 20 328 research participants of European ancestry

Sanchez‐Roige, Sandra; Fontanillas, Pierre; Elson, Sarah L.; Gray, Joshua C.; Wit, Harriet de; Davis, Lea K.; MacKillop, James; Palmer, Abraham A.

doi:10.1111/adb.12574

Cited by 98 publications

(120 citation statements)

References 82 publications

Supporting

Mentioning

105

Contrasting

Order By: Relevance

“…Broad sense heritability estimates of 25-61% for alcohol consumption have previously been reported from studies of twins 1, 2, 5 . The SNP effects for alcohol consumption were estimated at 6%, which again are lower than, but closer to, estimates reported in the UK Biobank for alcohol consumption (13%) and AUDIT scores in the 23andMe sample (12%) 28,36 . Previous studies have suggested that genetic interactions and improper modeling of the environment can inflate heritability estimates 37,38 .…”

Section: Discussionsupporting

confidence: 42%

Genetic and shared couple environmental contributions to smoking and alcohol use in the UK population

Clarke

Adams

Howard

et al. 2019

Preprint

View full text Add to dashboard Cite

Alcohol use and smoking are leading causes of death and disability worldwide. Both genetic and environmental factors have been shown to influence individual differences in the use of these substances. In the present study we tested whether genetic factors, modelled alongside common family environment, explained phenotypic variance in alcohol use and smoking behaviour in the Generation Scotland (GS) family sample of up to 19,377 individuals. SNP and pedigree-associated effects combined explained between 18% and 41% of the variance in substance use. Shared couple effects explained a significant amount of variance across all substance use traits, particularly alcohol intake, for which 38% of the phenotypic variance was explained. We tested whether the within-couple substance use correlations were due to assortative mating by testing the association between partner polygenic risk scores in 34,987 couple pairs from the UK Biobank (UKB). Only couples' smoking status PRSs were significantly associated (b=0.01, S.E=0.005, p=0.02). However, an individual's alcohol PRS was associated with their partner's phenotype (b=0.04, S.E=0.007, p < 2 x 10 -7 ). In support of this, G carriers of a functional ADH1B polymorphism (rs1229984), known to be associated with greater alcohol intake, were found to consume less alcohol if they had a partner who carried an A allele at this SNP. Together these results show that the shared couple environment contributes significantly to patterns of substance use. It is unclear whether this is due to shared environmental factors, assortative mating, or indirect genetic effects. Future studies would benefit from longitudinal data and larger sample sizes to assess this further.

show abstract

Section: Discussionsupporting

confidence: 42%

Genetic and shared couple environmental contributions to smoking and alcohol use in the UK population

Clarke

Adams

Howard

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…This approach has allowed for the relatively rapid collection of much larger sample sizes (e.g. >100,000s individuals) and has identified numerous loci associated with both pharmacokinetic and pharmacodynamic factors that influence alcohol consumption, including ADH1B/ADH1C/ADH5 (9)(10)(11), KLB (encoding β -klotho) (9,11,12) and GCKR, encoding the glucokinase regulatory protein (9,11). However, the genetic overlap between alcohol consumption (units per week) and DSM-IV diagnosed alcohol dependence is moderate (r g = 0.38) (13), reinforcing the notion that alcohol consumption cannot be used as a surrogate for alcohol dependence or AUD.…”

Section: Introductionmentioning

confidence: 99%

“…Linkage Disequilibrium Score regression (LDSC) (16) was used to calculate genetic correlations between AUDIT measures and other substance use, psychiatric, and behavioral traits. We also calculated genetic correlations with obesity and blood lipid traits, as these have previously been shown to associate with alcohol consumption (9,10). We hypothesized that AUDIT-P would correlate more strongly with measures of hazardous substance use, including alcohol dependence, and other psychiatric conditions.…”

Section: Introductionmentioning

confidence: 99%

Genome-wide association study meta-analysis of the Alcohol Use Disorder Identification Test (AUDIT) in two population-based cohorts (N=141,932)

Sanchez‐Roige

Palmer

Fontanillas³

et al. 2018

Preprint

Self Cite

View full text Add to dashboard Cite

words]Alcohol use disorders (AUD) are common conditions that have enormous social and economic consequences. We obtained quantitative measures using the Alcohol Use Disorder Identification Test (AUDIT) from two population-based cohorts of European ancestry: UK Biobank (UKB; N=121,604) and 23andMe (N=20,328) and performed a genome-wide association study (GWAS) meta-analysis. We also performed GWAS for AUDIT items 1-3, which focus on consumption (AUDIT-C), and for items 4-10, which focus on the problematic consequences of drinking (AUDIT-P). The GWAS meta-analysis of AUDIT total score identified 10 associated risk loci. Novel associations localized to genes including JCAD and SLC39A13;we also replicated previously identified signals in the genes ADH1B, ADH1C, KLB, and GCKR.The dimensions of AUDIT showed positive genetic correlations with alcohol consumption (r g =0.76-0.92) and Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) alcohol dependence (r g =0.33-0.63). AUDIT-P and AUDIT-C showed significantly different patterns of association across a number of traits, including psychiatric disorders. AUDIT-P was positively genetically correlated with schizophrenia (r g =0.22, p=3.0x10 -10 ), major depressive disorder (r g =0.26, p=5.6x10 -3 ), and attention-deficit/hyperactivity disorder (ADHD; r g =0.23, p=1.1x10 -5 ),whereas AUDIT-C was negatively genetically correlated with major depressive disorder (r g =-0.24, p=3.7x10 -3 ) and ADHD (r g =-0.10, p=1.8x10 -2 ). We also used the AUDIT data in the UKB to identify thresholds for dichotomizing AUDIT total score that optimize genetic correlations with DSM-IV alcohol dependence. Coding individuals with AUDIT total score of ≤ 4 as controls and ≥ 12 as cases produced a high genetic correlation with DSM-IV alcohol dependence (r g =0.82, p=3.2x10 -6 ) while retaining most subjects. We conclude that AUDIT scores ascertained in population-based cohorts can be used to explore the genetic basis of both alcohol consumption and AUD.

show abstract

“…Recruitment occurred over an approximately four-month period in 2015. This sample has been extensively described elsewhere (27,28). Sociodemographic details are described in the Supplementary Table 1.…”

Section: Samplementioning

confidence: 99%

Genome-wide association studies of impulsive personality traits (BIS-11 and UPPSP) and drug Experimentation in up to 22,861 adult research participants

Sanchez‐Roige

Fontanillas

Elson

et al. 2018

Preprint

Self Cite

View full text Add to dashboard Cite

Background: Impulsive personality traits are complex heritable traits that are governed by frontalsubcortical circuits and are associated with numerous neuropsychiatric disorders, particularly drug abuse. Methods:In collaboration with the genetics company 23andMe, Inc., we performed several genome-wide association studies (GWAS) on measures of impulsive personality traits (the short version of the UPPSP Impulsive Behavior Scale, and the Barratt Impulsiveness Scale ) and drug experimentation (the number of drug classes an individual has tried in their lifetime) in up to 22,861 male and female adult research participants of European ancestry. Results: Impulsive personality traits and drug experimentation showed SNP-heritabilities that ranged from 5 to 11%. Genetic variants in the CADM2 locus were significantly associated with the UPPSP Sensation Seeking subscale (P = 8.3 × 10 −9 , rs139528938) and showed a suggestive association with drug experimentation (P = 3.0 × 10 −7 , rs2163971; r 2 = 0.68 with rs139528938); CADM2 has been previously associated with measures of risky behaviors and self-reported risk tolerance, cannabis initiation, alcohol consumption, as well as information speed processing, body mass index (BMI) variation and obesity. Furthermore, genetic variants in the CACNA1I locus were significantly associated with the UPPSP Negative Urgency subscale (P = 3.8 × 10 −8 , rs199694726). Multiple subscales from both UPPSP and BIS showed strong genetic correlations (>0.5) with drug experimentation and other substance use traits measured in independent cohorts, including smoking initiation, and lifetime cannabis use. Several UPPSP and BIS subscales were genetically correlated with attention-deficit/hyperactivity disorder (rg = 0.30-0.51, p < 8.69 x 10 −3 ), supporting their validity as endophenotypes. Conclusions: Our findings demonstrate a role for common genetic contributions to individual differences in impulsivity.Furthermore, our study is the first to provide a genetic dissection of the relationship between different types of impulsive personality traits and various psychiatric disorders. Sanchez-Roige S

show abstract

Genome‐wide association study of alcohol use disorder identification test (AUDIT) scores in 20 328 research participants of European ancestry

Cited by 98 publications

References 82 publications

Genetic and shared couple environmental contributions to smoking and alcohol use in the UK population

Genetic and shared couple environmental contributions to smoking and alcohol use in the UK population

Genome-wide association study meta-analysis of the Alcohol Use Disorder Identification Test (AUDIT) in two population-based cohorts (N=141,932)

Genome-wide association studies of impulsive personality traits (BIS-11 and UPPSP) and drug Experimentation in up to 22,861 adult research participants

Contact Info

Product

Resources

About