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P11 The association of alcohol PRS on mental health phenotypes: a PheWAS in the avon longitudinal study of parents and children (ALSPAC)
  1. KE Easey1,2,
  2. E Haan1,2,
  3. L Schellas1,2,
  4. H Sallis1,2,
  5. R Wootton1,2,
  6. MR Munafò1,2,
  7. NJ Timpson3,
  8. L Zuccolo2,3
  1. 1School of Psychological Science, University of Bristol, Bristol, UK
  2. 2MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK
  3. 3Department of Population Health Sciences, University of Bristol, Bristol, UK


Background An emerging technique is a Phenome Wide Association Study (PheWAS), which reverses the phenotype to genotype methods used within a GWAS, instead taking a pre-determined set of genetic variants, and testing which of a wide range of phenotypes these genetic variants may be associated with. We can further investigate the genetic architecture of multiple traits and disease outcomes through linking a chosen genetic variant to multiple phenotypes, in varying populations.

In this study we constructed polygenic risk scores (PRS) from single nucleotide polymorphisms (SNPs) shown to be robustly related to alcohol use, to test:

  1. These genetic signals within two sub populations of adolescents, and for pregnant women.

  2. If there are any associations (other than with alcohol use) of these PRS with many mental health phenotypes.

  3. Intrauterine effects of Maternal PRS for alcohol use for associations with offspring phenotypes.

Methods Participants were mothers and offspring from the Avon Longitudinal Study of Parents and Children (ALSPAC). Participants were genotyped and PRS were constructed based on genome-wide significant SNPs for alcohol consumption. Targeted phenotypes were selected from substance use (n=22) and mental health/behavioural variables (n=91) within ALSPAC. Linear and logistic regression analyses were used to investigate if PRS for alcohol use were associated with alcohol use (mothers in pregnancy; children) and health phenotypes (mothers during pregnancy; children both pre-alcohol use around ages 7–10, and post-alcohol use around ages 13–23).

Results The PRS were associated with multiple alcohol consumption phenotypes (strongest signal for alcohol amount at 18 weeks gestation: p=1.01×10-5) in pregnant mothers. There was an effect of maternal PRS for alcohol use on mother’s perinatal depression (p=0.02), offspring intellect (p=0.016), and ADHD (p =0.04).

Discussion The effects of alcohol PRS previously found in the general population are also shown during pregnancy. We found an intrauterine effect of alcohol PRS on offspring intellect and ADHD. The effects shown are not due to offspring’s own alcohol use, as these effects were not found within the child’s analyses.

  • alcohol mental health epidemiology

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