Exploration of a Polygenic Risk Score for Alcohol Consumption: A Longitudinal Analysis from the ALSPAC Cohort

Michelle Taylor, Andrew J Simpkin, Philip C Haycock, Frank Dudbridge and Luisa Zuccolo

PLOS ONE, 2016, vol. 11, issue 11, 1-15

Abstract: Background: Uncertainty remains about the true extent by which alcohol consumption causes a number of health outcomes. Genetic variants, or combinations of variants built into a polygenic risk score (PGRS), can be used in an instrumental variable framework to assess causality between a phenotype and disease outcome of interest, a method known as Mendelian randomisation (MR). We aimed to identify genetic variants involved in the aetiology of alcohol consumption, and develop a PGRS for alcohol. Methods: Repeated measures of alcohol consumption from mothers and their offspring were collected as part of the Avon Longitudinal Study of Parents and Children. We tested the association between 89 SNPs (identified from either published GWAS data or from functional literature) and repeated measures of alcohol consumption, separately in mothers (from ages 28–48) and offspring (from ages 15–21) who had ever reported drinking. We modelled log units of alcohol using a linear mixed model and calculated beta coefficients for each SNP separately. Cross-validation was used to determine an allelic score for alcohol consumption, and the AVENGEME algorithm employed to estimate variance of the trait explained. Results: Following correction for multiple testing, one SNP (rs1229984) showed evidence for association with alcohol consumption (β = -0.177, SE = 0.042, p =

Date: 2016
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0167360

DOI: 10.1371/journal.pone.0167360

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