School Achievement, IQ, and Risk of Alcohol Use Disorder: A Prospective, Co-Relative Analysis in a Swedish National Cohort

Kendler, Kenneth S.; Sundquist, Jan; Sundquist, Kristina

doi:10.15288/jsad.2017.78.186

Cited by 13 publications

(14 citation statements)

References 26 publications

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“…AUDIT-C was positively genetically correlated with overall health rating, HDL cholesterol concentration, and years of education, findings that are consistent with prior literature showing genetic correlation of these traits with alcohol consumption 7,8,21 . AUD was significantly genetically correlated with 111 traits or diseases, including negative genetic correlations with intelligence, years of education and quitting smoking, and positive genetic correlations with insomnia, ever having smoked and most psychiatric disorders, findings that are consistent with phenotypic associations in the epidemiological literature 35–37 and genetic correlations reported from the UKBB and 23andMe GWASs and their meta-analysis 7,8,21 . The opposite genetic correlations seen for some traits may be driven by low-effect variants, as we find close to 100% consistency in the direction of effect for the most significantly associated SNPs for both AUDIT-C and AUD.…”

Section: Discussionsupporting

confidence: 80%

Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations

et al. 2019

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Alcohol consumption level and alcohol use disorder (AUD) diagnosis are moderately heritable traits. We conduct genome-wide association studies of these traits using longitudinal Alcohol Use Disorder Identification Test-Consumption (AUDIT-C) scores and AUD diagnoses in a multi-ancestry Million Veteran Program sample ( N = 274,424). We identify 18 genome-wide significant loci: 5 associated with both traits, 8 associated with AUDIT-C only, and 5 associated with AUD diagnosis only. Polygenic Risk Scores (PRS) for both traits are associated with alcohol-related disorders in two independent samples. Although a significant genetic correlation reflects the overlap between the traits, genetic correlations for 188 non-alcohol-related traits differ significantly for the two traits, as do the phenotypes associated with the traits’ PRS. Cell type group partitioning heritability enrichment analyses also differentiate the two traits. We conclude that, although heavy drinking is a key risk factor for AUD, it is not a sufficient cause of the disorder.

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Section: Discussionsupporting

confidence: 80%

Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations

et al. 2019

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“…AUDIT-C was positively genetically correlated with overall health rating, HDL cholesterol concentration, and years of education, findings that are consistent with prior literature showing genetic correlation of these traits with alcohol consumption 7,8,21 . AUD was significantly genetically correlated with 111 traits or diseases, including negative genetic correlations with intelligence, years of education and quitting smoking, and positive genetic correlations with insomnia, ever having smoked and most psychiatric disorders, findings that are consistent with phenotypic associations in the epidemiological literature 35–37 and genetic correlations reported from the UKBB and 23andMe GWASs and their meta-analysis 7,8,21 . Further, in the MVP sample, the AUD PRS was significantly positively associated with tobacco use and multiple psychiatric disorders, whereas the AUDIT-C PRS was not.…”

Section: Discussionsupporting

confidence: 80%

Genome-wide Association Study of Alcohol Consumption and Use Disorder in Multiple Populations (N = 274,424)

Kranzler

Zhou

Kember

et al. 2019

Preprint

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SummaryAlthough alcohol consumption level and alcohol use disorder (AUD) diagnosis are both moderately heritable, their genetic risks and overlap are not well understood. We conducted genome-wide association studies of these traits using longitudinal Alcohol Use Disorder Identification Test-Consumption (AUDIT-C) scores (reflecting alcohol consumption) and AUD diagnoses from electronic health records (EHRs) in a single, large multi-ancestry Million Veteran Program sample. Meta-analysis across population groups (N = 274,424) identified 18 genome-wide significant loci, 5 of which were associated with both traits and 13 with either AUDIT-C (N = 8) or AUD (N = 5). A significant genetic correlation between the traits reflects this overlap. However, downstream analyses revealed biologically meaningful points of divergence. Cell-type group partitioning heritability enrichment analyses indicated that central nervous system was the most significant cell type for AUDIT-C and the only significant cell type for AUD. Polygenic risk scores (PRS) for both traits were associated with alcohol-related disorders in two independent samples. Genetic correlations for 188 non-alcohol-related traits were significantly different for the two traits, as were the phenotypes associated with the traits’ polygenic risk scores. We conclude that EHR-derived, longitudinal, repeated measures of alcohol consumption level and AUD diagnosis can facilitate genetic discovery and help to elucidate the relationship between drinking level and AUD risk. Finally, although heavy drinking is a key risk factor for AUD, it is not a sufficient cause of the disorder.

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“…We used conditional logistic regression, with a separate stratum for each case and their control(s), in which we compare AUD in the case (i.e., AUD during pregnancy) with AUD in the controls (i.e., AUD during a non-pregnant period). Model 1 was only a crude model, whereas in model 2 we adjusted for average parental educational [(1) <=9 years, (2) 10-11 years, (3) 12 years or more] and school achievement of the individual (see (28) for how school achievement was defined). Odds ratios between 0 and 1 would indicate reduced risk for AUD during pregnancy (i.e., a protective effect of pregnancy), while odds ratios >1 would indicate increased risk.…”

Section: Statistical Analysesmentioning

confidence: 99%

Protective Effects of Pregnancy on Risk of Alcohol Use Disorder

Edwards

Svikis

Sundquist³

et al. 2019

AJP

Self Cite

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Objective: The authors sought to clarify the etiology of the association between pregnancy and Alcohol Use Disorder (AUD). Method: The authors utilized longitudinal, population-wide Swedish medical, pharmacy, and criminal registries to evaluate whether rates of AUD are lower during pregnancy. They compared pregnant women born 1975-1992 (N=322,029) to matched population controls, to female relatives discordant for pregnancy, and to within-individual pre-and post-pregnancy periods. They further compared AUD rates between pregnant women and their partners. Results: Pregnancy was inversely associated with AUD across all analyses (odds ratio=0.17-0.32). In co-relative analyses, the strength of the association increased among more closely related individuals. Within individuals, AUD rates were substantially decreased during pregnancy relative to the pre-pregnancy period (odds ratio=0.25-0.26), and remained reduced during post-partum periods (odds ratio=0.23-0.31). Results were similar for second pregnancies (odds ratio=0.23). The partners of pregnant women also exhibited reductions in AUD (odds ratio=0.45). Among women who became pregnant at earlier ages and those with a history of criminal behavior, the pregnancy-AUD association was especially pronounced (interaction p<0.01), but no moderation was observed for a personal or maternal parental AUD history. Conclusions: Findings suggest that pregnancy plays a critical, and likely causal, motivational role in reducing AUD risk among women and, to a lesser extent, their partners. These results extend the understanding of the relationship between pregnancy and alcohol use, demonstrating that even severe outcomes such as AUD are subject to the protective effects of pregnancy.

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School Achievement, IQ, and Risk of Alcohol Use Disorder: A Prospective, Co-Relative Analysis in a Swedish National Cohort

Cited by 13 publications

References 26 publications

Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations

Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations

Genome-wide Association Study of Alcohol Consumption and Use Disorder in Multiple Populations (N = 274,424)

Protective Effects of Pregnancy on Risk of Alcohol Use Disorder

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