RT Journal Article
SR Electronic
T1 Exploring the genetic architecture of inflammatory bowel disease by whole genome sequencing identifies association at <em>ADCY7</em>
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 058347
DO 10.1101/058347
A1 Yang Luo
A1 Katrina M. de Lange
A1 Luke Jostins
A1 Loukas Moutsianas
A1 Joshua Randall
A1 Nicholas A. Kennedy
A1 Christopher A. Lamb
A1 Shane McCarthy
A1 Tariq Ahmad
A1 Cathryn Edwards
A1 Eva Goncalves Serra
A1 Ailsa Hart
A1 Chris Hawkey
A1 John C. Mansfield
A1 Craig Mowat
A1 William G. Newman
A1 Sam Nichols
A1 Martin Pollard
A1 Jack Satsangi
A1 Alison Simmons
A1 Mark Tremelling
A1 Holm Uhlig
A1 David C. Wilson
A1 James C. Lee
A1 Natalie J. Prescott
A1 Charlie W. Lees
A1 Christopher G. Mathew
A1 Miles Parkes
A1 Jeffrey C. Barrett
A1 Carl A. Anderson
YR 2016
UL http://biorxiv.org/content/early/2016/06/11/058347.abstract
AB In order to further resolve the genetic architecture of the inflammatory bowel diseases, ulcerative colitis and Crohn’s disease, we sequenced the whole genomes of 4,280 patients at low coverage, and compared them to 3,652 previously sequenced population controls across 73.5 million variants. To increase power we imputed from these sequences into new and existing GWAS cohorts, and tested for association at ~12 million variants in a total of 16,432 cases and 18,843 controls. We discovered a 0.6% frequency missense variant in ADCY7 that doubles risk of ulcerative colitis, and offers insight into a new aspect of disease biology. Despite good statistical power, we did not identify any other new low-frequency risk variants, and found that such variants as a class explained little heritability. We did detect a burden of very rare, damaging missense variants in known Crohn’s disease risk genes, suggesting that more comprehensive sequencing studies will continue to improve our understanding of the biology of complex diseases.