Phenome-wide association studies across large population cohorts support drug target validation

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http://hdl.handle.net/10138/260556

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23andMe Res Team 2018 , ' Phenome-wide association studies across large population cohorts support drug target validation ' , Nature Communications , vol. 9 , 4285 . https://doi.org/10.1038/s41467-018-06540-3

Title: Phenome-wide association studies across large population cohorts support drug target validation
Author: 23andMe Res Team
Date: 2018-10-16
Language: eng
Number of pages: 13
Belongs to series: Nature Communications
ISSN: 2041-1723
URI: http://hdl.handle.net/10138/260556
Abstract: Phenome-wide association studies (PheWAS) have been proposed as a possible aid in drug development through elucidating mechanisms of action, identifying alternative indications, or predicting adverse drug events (ADEs). Here, we select 25 single nucleotide polymorphisms (SNPs) linked through genome-wide association studies (GWAS) to 19 candidate drug targets for common disease indications. We interrogate these SNPs by PheWAS in four large cohorts with extensive health information (23andMe, UK Biobank, FINRISK, CHOP) for association with 1683 binary endpoints in up to 697,815 individuals and conduct meta-analyses for 145 mapped disease endpoints. Our analyses replicate 75% of known GWAS associations (P<0.05) and identify nine study-wide significant novel associations (of 71 with FDR <0.1). We describe associations that may predict ADEs, e.g., acne, high cholesterol, gout, and gallstones with rs738409 (p.I148M) in PNPLA3 and asthma with rs1990760 (p.T946A) in IFIH1. Our results demonstrate PheWAS as a powerful addition to the toolkit for drug discovery.
Subject: SYSTEMIC-LUPUS-ERYTHEMATOSUS
INFLAMMATORY-BOWEL-DISEASE
ELECTRONIC HEALTH RECORDS
WHOLE-GENOME ASSOCIATION
CORONARY-ARTERY-DISEASE
FALSE DISCOVERY RATE
BODY-MASS INDEX
GENETIC INFLUENCES
LARGE-SCALE
RISK LOCI
3111 Biomedicine
3142 Public health care science, environmental and occupational health
3121 General medicine, internal medicine and other clinical medicine
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