@article{3256,
  keywords = {Asthma, 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},
  author = {Dorothée Diogo and Chao Tian and Christopher S. Franklin and Mervi Alanne-Kinnunen and Michael March and Chris C. A. Spencer and Ciara Vangjeli and Michael E. Weale and Hannele Mattsson and Elina Kilpeläinen and Patrick M. A. Sleiman and Dermot F. Reilly and Joshua McElwee and Joseph C. Maranville and Arnaub K. Chatterjee and Aman Bhandari and Khanh-Dung H. Nguyen and Karol Estrada and Mary-Pat Reeve and Janna Hutz and Nan Bing and Sally John and Daniel G. MacArthur and Veikko Salomaa and Samuli Ripatti and Hakon Hakonarson and Mark J. Daly and Aarno Palotie and David A. Hinds and Peter Donnelly and Caroline S. Fox and Aaron G. Day-Williams and Robert M. Plenge and Heiko Runz},
  title = {Phenome-wide association studies across large population cohorts support drug target validation},
  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.},
  year = {2018},
  journal = {Nature Communications},
  volume = {9},
  pages = {4285},
  month = {2018-10-16},
  issn = {2041-1723},
  doi = {10.1038/s41467-018-06540-3},
  language = {eng},
}