Polygenic risk scores: pleiotropy and the effect of environment.
Age-related phenotypes
Aging
Environment
Exogenous heterogeneity
Genome-wide association studies
Health span
Life span
Pleiotropy
Polygenic risk score
Journal
GeroScience
ISSN: 2509-2723
Titre abrégé: Geroscience
Pays: Switzerland
ID NLM: 101686284
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
08
01
2020
accepted:
08
05
2020
pubmed:
4
6
2020
medline:
28
4
2021
entrez:
4
6
2020
Statut:
ppublish
Résumé
Polygenic risk scores (PRSs) discriminate trait risks better than single genetic markers because they aggregate the effects of risk alleles from multiple genetic loci. Constructing pleiotropic PRSs and understanding heterogeneity, and the replication of PRS-trait associations can strengthen its applications. By using variational Bayesian multivariate high-dimensional regression, we constructed pleiotropic PRSs jointly associated with body mass index, systolic and diastolic blood pressure, total and high-density lipoprotein cholesterol in a sample of 18,108 Caucasians from three independent cohorts. We found that dissecting heterogeneity associated with birth year, which is a proxy of exogenous exposures, improved the replication of significant PRS-trait associations from 37.5% (6 of 16) in the entire sample to 90% (18 of 20) in the more homogeneous sample of individuals born before the year 1925. Our findings suggest that secular changes in exogenous exposures may substantially modify pleiotropic risk profiles affecting translation of genetic discoveries into health care.
Identifiants
pubmed: 32488673
doi: 10.1007/s11357-020-00203-2
pii: 10.1007/s11357-020-00203-2
pmc: PMC7732954
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1635-1647Subventions
Organisme : NIA NIH HHS
ID : P01 AG043352
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG065477
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG047310
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG061853
Pays : United States
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