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Diverticular disease is characterized by pouches (that is, diverticulae) due to weakness in the bowel wall, which can become infected and inflamed causing diverticulitis, with potentially severe complications. Here, we test 32.4 million sequence variants identified through whole-genome sequencing (WGS) of 15,220 Icelanders for association with diverticular disease (5,426 cases) and its more severe form diverticulitis (2,764 cases). Subsequently, 16 sequence variants are followed up in a diverticular disease sample from Denmark (5,970 cases, 3,020 controls). In the combined Icelandic and Danish data sets we observe significant association of intronic variants in  ARHGAP15  (Rho GTPase-activating protein 15; rs4662344-T:  P= 1.9 × 10 −18 , odds ratio (OR)=1.23) and  COLQ  (collagen-like tail subunit of asymmetric acetylcholinesterase; rs7609897-T:  P= 1.5 × 10 −10 , OR=0.87) with diverticular disease and in  FAM155A  (family with sequence similarity 155A; rs67153654-A:  P= 3.0 × 10 −11 , OR=0.82) with diverticulitis. These are the first loci shown to associate with diverticular disease in a genome-wide study.

Sequence variants in ARHGAP15, COLQ and FAM155A associate with diverticular disease and diverticulitis