Common variation in FAM155A is associated with diverticulitis but not diverticulosis

• Published in: Scientific reports Vol. 10; no. 1; p. 1658
• Main Authors: Reichert, Matthias C., Kupcinskas, Juozas, Schulz, Antje, Schramm, Christoph, Weber, Susanne N., Krawczyk, Marcin, Jüngst, Christoph, Casper, Markus, Grünhage, Frank, Appenrodt, Beate, Zimmer, Vincent, Tamelis, Algimantas, Lukosiene, Jaune I., Pauziene, Neringa, Kiudelis, Gediminas, Jonaitis, Laimas, Goeser, Tobias, Malinowski, Maciej, Glanemann, Matthias, Kupcinskas, Limas, Lammert, Frank
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03-02-2020; Nature Publishing Group
• Subjects: 45/22; 631/208/727/2000; 692/4020/1503/1581/1392; Acetylcholinesterase; Acetylcholinesterase - genetics; Aged; Cofactors; Cohort Studies; Collagen (type I); Collagen - genetics; Colon; Colonoscopy; Diverticulitis, Colonic - genetics; Diverticulosis, Colonic - genetics; Female; Genetic Association Studies; Genetic diversity; Genetic Predisposition to Disease; Genetic variance; Genome-wide association studies; Genome-Wide Association Study; Genomes; Germany; GTPase-activating protein; GTPase-Activating Proteins - genetics; Guanosine triphosphatases; Humanities and Social Sciences; Humans; Inflammation; Lithuania; Male; Membrane Proteins - genetics; Middle Aged; multidisciplinary; Muscle Proteins - genetics; Polymorphism, Single Nucleotide; Regression analysis; Risk Factors; Science; Science (multidisciplinary); Lithuania; Germany
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-58437-1

Colonic diverticulosis is a very common condition. Many patients develop diverticulitis or other complications of diverticular disease. Recent genome-wide association studies (GWAS) consistently identified three major genetic susceptibility factors for both conditions, but did not discriminate diverticulititis and diverticulosis in particular due the limitations of registry-based approaches. Here, we aimed to confirm the role of the identified variants for diverticulosis and diverticulitis, respectively, within a well-phenotyped cohort of patients who underwent colonoscopy. Risk variants rs4662344 in Rho GTPase-activating protein 15 (
ARHGAP15
), rs7609897 in collagen-like tail subunit of asymmetric acetylcholinesterase (
COLQ
) and rs67153654 in family with sequence similarity 155 A (
FAM155A
) were genotyped in 1,332 patients. Diverticulosis was assessed by colonoscopy, and diverticulitis by imaging, clinical symptoms and inflammatory markers. Risk of diverticulosis and diverticulitis was analyzed in regression models adjusted for cofactors. Overall, the variant in
FAM155A
was associated with diverticulitis, but not diverticulosis, when controlling for age, BMI, alcohol consumption, and smoking status (OR
adjusted
0.49 [95% CI 0.27–0.89], p = 0.002). Our results contribute to the assessment specific genetic variants identified in GWAS in the predisposition to the development of diverticulitis in patients with diverticulosis.