Female-specific Association Between Variants on Chromosome 9 and Self-reported Diagnosis of Irritable Bowel Syndrome.

Bonfiglio F, Zheng T, Garcia-Etxebarria K, Hadizadeh F, Bujanda L, Bresso F, Agreus L, Andreasson A, Dlugosz A, Lindberg G, Schmidt PT, Karling P, Ohlsson B, Simren M, Walter S, Nardone G, Cuomo R, Usai-Satta P, Galeazzi F, Neri M, Portincasa P, Bellini M, Barbara G, Latiano A, Hübenthal M, Thijs V, Netea MG, Jonkers D, Chang L, Mayer EA, Wouters MM, Boeckxstaens G, Camilleri M, Franke A, Zhernakova A, D'Amato M

Gastroenterology - (-) - [2018-04-04; online 2018-04-04]

Genetic factors are believed to affect risk for irritable bowel syndrome (IBS), but there have been no sufficiently powered and adequately sized studies. To identify DNA variants associated with IBS risk, we performed a genome-wide association study (GWAS) of the large UK Biobank population-based cohort, which includes genotype and health data from 500,000 participants. We studied 7,287,191 high-quality single-nucleotide polymorphisms in individuals who self-reported a doctor's diagnosis of IBS (cases; m=9576) compared to the remainder of the cohort (controls; n=336,499) (mean age of study subjects, 40-69 years). Genome-wide significant findings were further investigated in 2045 patients with IBS from tertiary centers and 7955 population controls from Europe and the United States, and a small general population sample from Sweden (n=249). Functional annotation of GWAS results was carried out by integrating data from multiple biorepositories, to obtain biological insights from the observed associations. We identified a genome-wide significant association on chromosome 9q31.2 (SNP rs10512344; P=3.57×10 In a sufficiently powered GWAS of IBS, we associated variants at the locus 9q32.1 with risk of IBS in women. This observation may provide additional rationale for investigating the role of sex hormones and autonomic dysfunction in IBS.

Bioinformatics Support for Computational Resources [Service]

NGI Uppsala (SNP&SEQ Technology Platform) [Service]

National Genomics Infrastructure [Service]

PubMed 29626450

DOI 10.1053/j.gastro.2018.03.064

Crossref 10.1053/j.gastro.2018.03.064

pii: S0016-5085(18)30407-4