You are here

Nat Commun DOI:10.1038/s41467-018-06540-3

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

Publication TypeJournal Article
Year of Publication2018
AuthorsDiogo, D, Tian, C, Franklin, CS, Alanne-Kinnunen, M, March, M, Spencer, CCA, Vangjeli, C, Weale, ME, Mattsson, H, Kilpeläinen, E, Sleiman, PMA, Reilly, DF, McElwee, J, Maranville, JC, Chatterjee, AK, Bhandari, A, Nguyen, K-DH, Estrada, K, Reeve, M-P, Hutz, J, Bing, N, John, S, MacArthur, DG, Salomaa, V, Ripatti, S, Hakonarson, H, Daly, MJ, Palotie, A, Hinds, DA, Donnelly, P, Fox, CS, Day-Williams, AG, Plenge, RM, Runz, H
JournalNat Commun
Date Published2018 10 16
KeywordsAsthma, Cohort Studies, Databases, Factual, Drug Discovery, Genetic Association Studies, Genetic Pleiotropy, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Interferon-Induced Helicase, IFIH1, Lipase, Membrane Proteins, Molecular Targeted Therapy, Phenotype, Polymorphism, Single Nucleotide, Reproducibility of Results, Thromboembolism, United Kingdom

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 


Alternate JournalNat Commun
PubMed ID30327483
PubMed Central IDPMC6191429