Exploring the genetic architecture of inflammatory bowel disease by whole genome sequencing identifies association at ADCY7

Citations Over Time

Abstract

Abstract 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.

Related Papers

• → Genetic Scoring Analysis: a way forward in Genome Wide Association Studies?(2009)26 cited
• → An Association Mapping Framework To Account for Potential Sex Difference in Genetic Architectures(2018)5 cited
• → Assessing the impact of missing genotype data in rare variant association analysis(2011)11 cited
• → Genetic Architecture of Complex Human Traits: What Have We Learned from Genome-Wide Association Studies?(2015)4 cited
• → Revealing the missing heritability via cross-validated genome-wide association studies(2013)1 cited