@article{3124854,
    title = "Exploring the genetics of irritable bowel syndrome: A GWA study in the general population and replication in multinational case-control cohorts",
    author = "Ek, W.E. and Reznichenko, A. and Ripke, S. and Niesler, B. and Zucchelli, M. and Rivera, N.V. and Schmidt, P.T. and Pedersen, N.L. and Magnusson, P. and Talley, N.J. and Holliday, E.G. and Houghton, L. and Gazouli, M. and Karamanolis, G. and Rappold, G. and Burwinkel, B. and Surowy, H. and Rafter, J. and Assadi, G. and Li, L. and Papadaki, E. and Gambaccini, D. and Marchi, S. and Colucci, R. and Blandizzi, C. and Barbaro, R. and Karling, P. and Walter, S. and Ohlsson, B. and Tornblom, H. and Bresso, F. and Andreasson, A. and Dlugosz, A. and Simren, M. and Agreus, L. and Lindberg, G. and Boeckxstaens, G. and Bellini, M. and Stanghellini, V. and Barbara, G. and Daly, M.J. and Camilleri, M. and Wouters, M.M. and D'Amato, M.",
    journal = "Gut Pathogens",
    year = "2015",
    volume = "64",
    number = "11",
    pages = "1774-1782",
    publisher = "BMJ Publishing Group",
    issn = "1757-4749",
    doi = "10.1136/gutjnl-2014-307997",
    keywords = "messenger RNA, adult;  Article;  controlled study;  female;  follow up;  gene expression;  gene function;  genetic association;  genetic risk;  genotype;  GRID2IP gene;  human;  irritable colon;  KDELR2 gene;  major clinical study;  male;  priority journal;  quality control;  quantitative trait locus;  questionnaire;  real time polymerase chain reaction;  rectum biopsy;  single nucleotide polymorphism;  Swedish citizen;  case control study;  clinical trial;  cohort analysis;  genetics;  international cooperation;  irritable colon;  middle aged;  multicenter study, Adult;  Case-Control Studies;  Cohort Studies;  Female;  Genome-Wide Association Study;  Humans;  Internationality;  Irritable Bowel Syndrome;  Male;  Middle Aged",
    abstract = "Objective: IBS shows genetic predisposition, but adequately powered gene-hunting efforts have been scarce so far. We sought to identify true IBS genetic risk factors by means of genome-wide association (GWA) and independent replication studies. Design: We conducted a GWA study (GWAS) of IBS in a general population sample of 11 326 Swedish twins. IBS cases (N=534) and asymptomatic controls (N=4932) were identified based on questionnaire data. Suggestive association signals were followed-up in 3511 individuals from six case-control cohorts. We sought genotype-gene expression correlations through single nucleotide polymorphism (SNP)-expression quantitative trait loci interactions testing, and performed in silico prediction of gene function. We compared candidate gene expression by real-time qPCR in rectal mucosal biopsies of patients with IBS and controls. Results: One locus at 7p22.1, which includes the genes KDELR2 (KDEL endoplasmic reticulum protein retention receptor 2) and GRID2IP (glutamate receptor, ionotropic, delta 2 (Grid2) interacting protein), showed consistent IBS risk effects in the index GWAS and all replication cohorts and reached p=9.31×10-6 in a meta-analysis of all datasets. Several SNPs in this region are associated with cis effects on KDELR2 expression, and a trend for increased mucosal KDLER2 mRNA expression was observed in IBS cases compared with controls. Conclusions: Our results demonstrate that general population-based studies combined with analyses of patient cohorts provide good opportunities for gene discovery in IBS. The 7p22.1 and other risk signals detected in this study constitute a good starting platform for hypothesis testing in future functional investigations. © 2015, BMJ Publishing Group. All rights reserved."
}