Meta-Analysis Increases to 71 the Tally of Confirmed Crohn’s Disease Susceptibility Loci

By Andre Franke, D. McGovern, J. Barrett, Kai Wang, Graham L. Radford-Smith, T. Ahmad, C. Lees, Tobias Balschun, James Lee, R. Roberts and 86 more. Nature Genetics, 2010

2,611 citations recorded by the source corpus.

We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10−8). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.

Subfields: Genetics, Immunology, Surgery

View Paper: https://www.semanticscholar.org/paper/8a9dcc30448c4d660abbce058c8ec7d1dba78976

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Citations in the corpus

JAK–STAT Signaling as a Target for Inflammatory and Autoimmune Diseases: Current and Future Prospects (2017, background): “For example, JAK2 polymorphisms are associated with Behçet’s disease, while single nucleotide polymorphisms in the TYK2 gene have been implicated in Crohn’s disease (CD) and lupus [25, 60, 61].”
Computational Drug Repositioning: From Data to Therapeutics (2013, background): “35 These studies suggest that the convergence of human genetics and pharmacology might high-light some of the better drug targets.”
All SNPs Are Not Created Equal: Genome-Wide Association Studies Reveal a Consistent Pattern of Enrichment among Functionally Annotated SNPs (2013, background): “Fourteen phenotypes, body mass index (BMI) [37], height, waist to hip ratio [38] (WHR), Crohn’s disease [39] (CD), ulcerative colitis [40] (UC), schizophrenia [41] (SCZ), bipolar disorder [42] (BD), smoking behavior as measured by cigarettes per day [43] (CPD), systolic and diastolic blood pressure ”
Panning for gold: ‘model‐X’ knockoffs for high dimensional controlled variable selection (2016, background): “Focusing on the clusters on chromosome 1, the same region on the IL23R gene was reported in Franke et al. (2010) to have by far the strongest signal (estimated odds ratio of 2.66, next highest was 1.53) among all the regions they identiﬁed.”