Characterization of alcohol polygenic risk scores in the context of mental health outcomes: Within-individual and intergenerational analyses in the Avon Longitudinal Study of Parents and Children.
Adolescent
Adult
Alcohol Drinking
/ genetics
Child
Child, Preschool
Depression
/ epidemiology
Female
Humans
Intergenerational Relations
Longitudinal Studies
Male
Maternal Health
/ trends
Mental Health
/ trends
Multifactorial Inheritance
/ genetics
Parents
/ psychology
Pregnancy
Pregnancy Complications
/ epidemiology
Prenatal Exposure Delayed Effects
/ epidemiology
Risk Factors
United Kingdom
/ epidemiology
ALSPAC
Alcohol
MR-PheWAS
Mental health
Polygenic risk score
Journal
Drug and alcohol dependence
ISSN: 1879-0046
Titre abrégé: Drug Alcohol Depend
Pays: Ireland
ID NLM: 7513587
Informations de publication
Date de publication:
01 04 2021
01 04 2021
Historique:
received:
28
08
2020
revised:
17
02
2021
accepted:
17
02
2021
pubmed:
7
3
2021
medline:
29
6
2021
entrez:
6
3
2021
Statut:
ppublish
Résumé
Heavy alcohol consumption often co-occurs with mental health problems; this could be due to confounding, shared biological mechanisms, or causal effects. Polygenic risk scores (PRS) for alcohol use can be used to explore this association at critical life stages. We characterized a PRS reliably associated with patterns of adult alcohol consumption by 1) validating whether it predicts own alcohol use at different life-stages (pregnancy, adolescence) of interest for mental health impact. Additionally, we explored associations of alcohol PRS on mental health phenotypes 2) within-individuals (using own alcohol PRS on own phenotypes) and 3) intergenerationally (using maternal alcohol PRS on offspring phenotypes). We used data from the Avon Longitudinal Study of Parents and Children (ALSPAC) (n = 960-7841). Additional substance abuse behaviors and mental health/behavioral outcomes were investigated (alcohol phenotypes n = 22; health phenotypes n = 91). Maternal alcohol PRS was associated with consumption during pregnancy (strongest signal: alcohol frequency at 18 weeks' gestation: β = 0.041, 95%CI = 0.0.02-0.06), p = 1.01 × 10 These alcohol PRS are a valid proxy for maternal alcohol use in pregnancy. Offspring alcohol PRS was not associated with drinking in adolescence. Consistently with results from different study designs, we found evidence that maternal alcohol PRS are associated with both prenatal depression and decreased offspring intellectual ability.
Sections du résumé
BACKGROUND
Heavy alcohol consumption often co-occurs with mental health problems; this could be due to confounding, shared biological mechanisms, or causal effects. Polygenic risk scores (PRS) for alcohol use can be used to explore this association at critical life stages.
DESIGN
We characterized a PRS reliably associated with patterns of adult alcohol consumption by 1) validating whether it predicts own alcohol use at different life-stages (pregnancy, adolescence) of interest for mental health impact. Additionally, we explored associations of alcohol PRS on mental health phenotypes 2) within-individuals (using own alcohol PRS on own phenotypes) and 3) intergenerationally (using maternal alcohol PRS on offspring phenotypes). We used data from the Avon Longitudinal Study of Parents and Children (ALSPAC) (n = 960-7841). Additional substance abuse behaviors and mental health/behavioral outcomes were investigated (alcohol phenotypes n = 22; health phenotypes n = 91).
FINDINGS
Maternal alcohol PRS was associated with consumption during pregnancy (strongest signal: alcohol frequency at 18 weeks' gestation: β = 0.041, 95%CI = 0.0.02-0.06), p = 1.01 × 10
CONCLUSIONS
These alcohol PRS are a valid proxy for maternal alcohol use in pregnancy. Offspring alcohol PRS was not associated with drinking in adolescence. Consistently with results from different study designs, we found evidence that maternal alcohol PRS are associated with both prenatal depression and decreased offspring intellectual ability.
Identifiants
pubmed: 33676074
pii: S0376-8716(21)00149-6
doi: 10.1016/j.drugalcdep.2021.108654
pmc: PMC8047864
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
108654Subventions
Organisme : Medical Research Council
ID : G0902144
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 202802/Z/16/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12013/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L022206/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G9815508
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C18281/A19169
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 102215/2/13/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00011/7
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_19009
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L033306/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_15018
Pays : United Kingdom
Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.
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