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

Dorothée Diogo (), Chao Tian, Christopher S. Franklin, Mervi Alanne-Kinnunen, Michael March, Chris C. A. Spencer, Ciara Vangjeli, Michael E. Weale, Hannele Mattsson, Elina Kilpeläinen, Patrick M. A. Sleiman, Dermot F. Reilly, Joshua McElwee, Joseph C. Maranville, Arnaub K. Chatterjee, Aman Bhandari, Khanh-Dung H. Nguyen, Karol Estrada, Mary-Pat Reeve, Janna Hutz, Nan Bing, Sally John, Daniel G. MacArthur, Veikko Salomaa, Samuli Ripatti, Hakon Hakonarson, Mark J. Daly, Aarno Palotie, David A. Hinds, Peter Donnelly, Caroline S. Fox, Aaron G. Day-Williams, Robert M. Plenge and Heiko Runz ()
Additional contact information
Dorothée Diogo: Merck Sharp & Dohme
Chao Tian: 23andMe Inc
Christopher S. Franklin: Genomics plc
Mervi Alanne-Kinnunen: University of Helsinki
Michael March: The Children’s Hospital of Philadelphia and University of Pennsylvania
Chris C. A. Spencer: Genomics plc
Ciara Vangjeli: Genomics plc
Michael E. Weale: Genomics plc
Hannele Mattsson: University of Helsinki
Elina Kilpeläinen: University of Helsinki
Patrick M. A. Sleiman: The Children’s Hospital of Philadelphia and University of Pennsylvania
Dermot F. Reilly: Merck Sharp & Dohme
Joshua McElwee: Merck Sharp & Dohme
Joseph C. Maranville: Merck Sharp & Dohme
Arnaub K. Chatterjee: Merck Sharp & Dohme
Aman Bhandari: Merck Sharp & Dohme
Khanh-Dung H. Nguyen: Biogen, Research and Early Development
Karol Estrada: Biogen, Research and Early Development
Mary-Pat Reeve: Eisai
Janna Hutz: Eisai
Nan Bing: Pfizer
Sally John: Biogen, Research and Early Development
Daniel G. MacArthur: Broad Institute of MIT and Harvard
Veikko Salomaa: National Institute for Health and Welfare
Samuli Ripatti: University of Helsinki
Hakon Hakonarson: The Children’s Hospital of Philadelphia and University of Pennsylvania
Mark J. Daly: Broad Institute of MIT and Harvard
Aarno Palotie: University of Helsinki
David A. Hinds: 23andMe Inc
Peter Donnelly: Genomics plc
Caroline S. Fox: Merck Sharp & Dohme
Aaron G. Day-Williams: Merck Sharp & Dohme
Robert M. Plenge: Merck Sharp & Dohme
Heiko Runz: Merck Sharp & Dohme

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: 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

Date: 2018
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DOI: 10.1038/s41467-018-06540-3

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