Rare and common variant discovery in complex disease: the IBD case study. (31st July 2019)

• Record Type: Journal Article
• Authors: Venkataraman, Guhan R; Rivas, Manuel A
• Is Part Of: Human molecular genetics. Volume 28:Number R2(2019)
• Page Start: R162
• Page End: R169
• Publication Date: 2019-07-31
• Subjects: statistical genetics -- rare variants -- crohns disease -- ulcerative colitis -- inflammatory bowel disease; Human molecular genetics -- Periodicals; Human chromosome abnormalities -- Periodicals; 572.8
• DOI: 10.1093/hmg/ddz189
• Languages: English
• ISSNs: 0964-6906

Abstract

Abstract: Complex diseases such as inflammatory bowel disease (IBD), which consists of ulcerative colitis and Crohn's disease, are a significant medical burden—70 000 new cases of IBD are diagnosed in the United States annually. In this review, we examine the history of genetic variant discovery in complex disease with a focus on IBD. We cover methods that have been applied to microsatellite, common variant, targeted resequencing and whole-exome and -genome data, specifically focusing on the progression of technologies towards rare-variant discovery. The inception of these methods combined with better availability of population level variation data has led to rapid discovery of IBD-causative and/or -associated variants at over 200 loci; over time, these methods have grown exponentially in both power and ascertainment to detect rare variation. We highlight rare-variant discoveries critical to the elucidation of the pathogenesis of IBD, including those in NOD2, IL23R, CARD9, RNF186 and ADCY7 . We additionally identify the major areas of rare-variant discovery that will evolve in the coming years. A better understanding of the genetic basis of IBD and other complex diseases will lead to improved diagnosis, prognosis, treatment and surveillance.