Sequence variants in ARHGAP15, COLQ and FAM155A associate with diverticular disease and diverticulitis
| Autor: | Kari Stefansson, Sigurgeir Olafsson, Bjarke Feenstra, Tryggvi Stefansson, Thorgeir E. Thorgeirsson, Mads Melbye, Gisli Masson, Patrick Sulem, Kristjan F. Alexandersson, Steinunn Gudmundsdottir, Ingileif Jonsdottir, Snaevar Sigurdsson, Henrik Stig Jørgensen, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Asgeir Sigurdsson, Erik Sørensen, Gisli H. Halldorsson, Jakob Burcharth, Andreas Nordholm-Carstensen, Jens S. Andersen, Emma Possfelt-Møller, Daniel F. Gudbjartsson, Henrik Ullum, Thorunn Rafnar |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Science Denmark Iceland General Physics and Astronomy Muscle Proteins Gastroenterology Polymorphism Single Nucleotide General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences 0302 clinical medicine Internal medicine COLQ medicine Humans Genetic Predisposition to Disease Diverticulitis Sequence (medicine) Aged Diverticular Diseases Multidisciplinary business.industry digestive oral and skin physiology GTPase-Activating Proteins food and beverages Membrane Proteins General Chemistry Odds ratio Middle Aged medicine.disease 3. Good health 030104 developmental biology Case-Control Studies Diverticular disease Acetylcholinesterase 030211 gastroenterology & hepatology Female Collagen business Bowel wall Genome-Wide Association Study |
| Zdroj: | Nature Communications Nature Communications, Vol 8, Iss 1, Pp 1-7 (2017) |
| ISSN: | 2041-1723 |
| Popis: | 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. A hallmark of diverticular disease is pouches in the bowel wall which can become infected and inflamed, causing the more severe diverticulitis. Here, the authors report the first genome-wide association study on these interconnected conditions and identify ARHGAP15, COLQ and FAM155A as novel risk loci. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|