Rare and common variant discovery in complex disease: the IBD case study.
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.
['Venkataraman|Guhan R|GR|', 'Rivas|Manuel A|MA|']
D044466:Asians D016022:Case-Control Studies D008040:Genetic Linkage D020022:Genetic Predisposition to Disease D055106:Genome-Wide Association Study D049673:History, 20th Century D049674:History, 21st Century D006801:Humans D015212:Inflammatory Bowel Diseases D015233:Models, Statistical D020641:Polymorphism, Single Nucleotide D018123:Receptors, Interleukin D044465:Whites D000073359:Whole Exome Sequencing
inflammatory bowel disease ulcerative colitis crohns disease rare variants statistical genetics