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Lookup NU author(s): Dr Chris LambORCiD,
Dr John Mansfield
This is the authors' accepted manuscript of an article that has been published in its final definitive form by Nature Publishing Group, 2017.
For re-use rights please refer to the publisher's terms and conditions.
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. We then imputed from these sequences into new and existing genome-wide association study cohorts and tested for association at similar to 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 the risk of ulcerative colitis. Despite good statistical power, we did not identify any other new low-frequency risk variants and found that such variants explained little heritability. We detected 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 understanding of the biology of complex diseases.
Author(s): Luo Y, de Lange KM, Jostins L, Moutsianas L, Randall J, Kennedy NA, Lamb CA, McCarthy S, Ahmad T, Edwards C, Serra EG, Hart A, Hawkey C, Mansfield JC, Mowat C, Newman WG, Nichols S, Pollard M, Satsangi J, Simmons A, Tremelling M, Uhlig H, Wilson DC, Lee JC, Prescott NJ, Lees CW, Mathew CG, Parkes M, Barrett JC, Anderson CA
Publication type: Article
Publication status: Published
Journal: Nature Genetics
Print publication date: 01/02/2017
Online publication date: 09/01/2017
Acceptance date: 07/12/2016
Date deposited: 09/01/2019
ISSN (print): 1061-4036
ISSN (electronic): 1546-1718
Publisher: Nature Publishing Group
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