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

Nat Commun 2017 06 6;8:15789. Epub 2017 Jun 6.

deCODE Genetics/Amgen Inc., Sturlugata 8, 101 Reykjavik, Iceland.

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, odds ratio (OR)=1.23) and COLQ (collagen-like tail subunit of asymmetric acetylcholinesterase; rs7609897-T: P=1.5 × 10, OR=0.87) with diverticular disease and in FAM155A (family with sequence similarity 155A; rs67153654-A: P=3.0 × 10, OR=0.82) with diverticulitis. These are the first loci shown to associate with diverticular disease in a genome-wide study.

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http://dx.doi.org/10.1038/ncomms15789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5467205PMC
June 2017
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References

(Supplied by CrossRef)

DJ Humes et al.
Dis. Colon Rectum 2016

RH Pfutzer et al.
Nat. Rev. Gastroenterol. Hepatol. 2015

A Tursi et al.
Ther. Adv. Gastroenterol. 2016

JE Everhart et al.
Gastroenterology 2009

MR Matrana et al.
Clin. Colon Rectal Surg. 2009

AA Sheth et al.
Am. J. Gastroenterol. 2008

AF Peery et al.
Curr. Gastroenterol. Rep. 2016

LL Strate et al.
Gastroenterology 2013

J Granlund et al.
Aliment Pharmacol. Ther. 2012

A Kong et al.
Nat. Genet. 2008

DF Gudbjartsson et al.
Nat. Genet. 2015

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