Citation

Rosoff DB, Clarke TK, Adams MJ, McIntosh AM, Davey Smith G, Jung J, Lohoff FW. Mol. Psychiatry 2019; ePub(ePub): ePub.

Affiliation

Section on Clinical Genomics and Experimental Therapeutics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA. falk.lohoff@nih.gov.

Copyright

(Copyright © 2019, Nature Publishing Group)

DOI

10.1038/s41380-019-0535-9

PMID

31649322

Abstract

Observational studies suggest that lower educational attainment (EA) may be associated with risky alcohol use behaviors; however, these findings may be biased by confounding and reverse causality. We performed two-sample Mendelian randomization (MR) using summary statistics from recent genome-wide association studies (GWAS) with >780,000 participants to assess the causal effects of EA on alcohol use behaviors and alcohol dependence (AD). Fifty-three independent genome-wide significant SNPs previously associated with EA were tested for association with alcohol use behaviors. We show that while genetic instruments associated with increased EA are not associated with total amount of weekly drinks, they are associated with reduced frequency of binge drinking ≥6 drinks (ß_IVW = -0.198, 95% CI, -0.297 to -0.099, P_IVW = 9.14 × 10^-5), reduced total drinks consumed per drinking day (ß_IVW = -0.207, 95% CI, -0.293 to -0.120, P_IVW = 2.87 × 10^-6), as well as lower weekly distilled spirits intake (ß_IVW = -0.148, 95% CI, -0.188 to -0.107, P_IVW = 6.24 × 10^-13). Conversely, genetic instruments for increased EA were associated with increased alcohol intake frequency (ß_IVW = 0.331, 95% CI, 0.267-0.396, P_IVW = 4.62 × 10^-24), and increased weekly white wine (ß_IVW = 0.199, 95% CI, 0.159-0.238, P_IVW = 7.96 × 10^-23) and red wine intake (ß_IVW = 0.204, 95% CI, 0.161-0.248, P_IVW = 6.67 × 10^-20). Genetic instruments associated with increased EA reduced AD risk: an additional 3.61 years schooling reduced the risk by ~50% (OR_IVW = 0.508, 95% CI, 0.315-0.819, P_IVW = 5.52 × 10^-3). Consistency of results across complementary MR methods accommodating different assumptions about genetic pleiotropy strengthened causal inference. Our findings suggest EA may have important effects on alcohol consumption patterns and may provide potential mechanisms explaining reported associations between EA and adverse health outcomes.

Language: en