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Genome-wide association analyses identify 39 new susceptibility loci for diverticular disease.
Nat Genet. 2018 Oct; 50(10):1359-1365.NGen

Abstract

Diverticular disease is common and has a high morbidity. Treatments are limited owing to the poor understanding of its pathophysiology. Here, to elucidate its etiology, we performed a genome-wide association study of diverticular disease (27,444 cases; 382,284 controls) from the UK Biobank and tested for replication in the Michigan Genomics Initiative (2,572 cases; 28,649 controls). We identified 42 loci associated with diverticular disease; 39 of these loci are novel. Using data-driven expression-prioritized integration for complex traits (DEPICT), we show that genes in these associated regions are significantly enriched for expression in mesenchymal stem cells and multiple connective tissue cell types and are co-expressed with genes that have a role in vascular and mesenchymal biology. Genes in these associated loci have roles in immunity, extracellular matrix biology, cell adhesion, membrane transport and intestinal motility. Phenome-wide association analysis of the 42 variants shows a common etiology of diverticular disease with obesity and hernia. These analyses shed light on the genomic landscape of diverticular disease.

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Authors+Show Affiliations

Maguire LH
Department of Surgery, Division of Colorectal Surgery, University of Michigan, Ann Arbor, MI, USA. maguirel@med.umich.edu.
Handelman SK
Department of Internal Medicine, Division of Gastroenterology, Ann Arbor, MI, USA.
Du X
Department of Internal Medicine, Division of Gastroenterology, Ann Arbor, MI, USA.
Chen Y
Department of Internal Medicine, Division of Gastroenterology, Ann Arbor, MI, USA.
Pers TH
The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
Speliotes EK
Department of Internal Medicine, Division of Gastroenterology, Ann Arbor, MI, USA. Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.

MeSH

AdultAgedCase-Control StudiesDiverticular DiseasesFemaleGenetic LociGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMiddle AgedPolymorphism, Single NucleotideQuantitative Trait LociUnited Kingdom

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30177863

Citation

Maguire, Lillias H., et al. "Genome-wide Association Analyses Identify 39 New Susceptibility Loci for Diverticular Disease." Nature Genetics, vol. 50, no. 10, 2018, pp. 1359-1365.
Maguire LH, Handelman SK, Du X, et al. Genome-wide association analyses identify 39 new susceptibility loci for diverticular disease. Nat Genet. 2018;50(10):1359-1365.
Maguire, L. H., Handelman, S. K., Du, X., Chen, Y., Pers, T. H., & Speliotes, E. K. (2018). Genome-wide association analyses identify 39 new susceptibility loci for diverticular disease. Nature Genetics, 50(10), 1359-1365. https://doi.org/10.1038/s41588-018-0203-z
Maguire LH, et al. Genome-wide Association Analyses Identify 39 New Susceptibility Loci for Diverticular Disease. Nat Genet. 2018;50(10):1359-1365. PubMed PMID: 30177863.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genome-wide association analyses identify 39 new susceptibility loci for diverticular disease. AU - Maguire,Lillias H, AU - Handelman,Samuel K, AU - Du,Xiaomeng, AU - Chen,Yanhua, AU - Pers,Tune H, AU - Speliotes,Elizabeth K, Y1 - 2018/09/03/ PY - 2018/03/08/received PY - 2018/07/23/accepted PY - 2018/9/5/pubmed PY - 2019/4/27/medline PY - 2018/9/5/entrez SP - 1359 EP - 1365 JF - Nature genetics JO - Nat Genet VL - 50 IS - 10 N2 - Diverticular disease is common and has a high morbidity. Treatments are limited owing to the poor understanding of its pathophysiology. Here, to elucidate its etiology, we performed a genome-wide association study of diverticular disease (27,444 cases; 382,284 controls) from the UK Biobank and tested for replication in the Michigan Genomics Initiative (2,572 cases; 28,649 controls). We identified 42 loci associated with diverticular disease; 39 of these loci are novel. Using data-driven expression-prioritized integration for complex traits (DEPICT), we show that genes in these associated regions are significantly enriched for expression in mesenchymal stem cells and multiple connective tissue cell types and are co-expressed with genes that have a role in vascular and mesenchymal biology. Genes in these associated loci have roles in immunity, extracellular matrix biology, cell adhesion, membrane transport and intestinal motility. Phenome-wide association analysis of the 42 variants shows a common etiology of diverticular disease with obesity and hernia. These analyses shed light on the genomic landscape of diverticular disease. SN - 1546-1718 UR - https://www.unboundmedicine.com/medline/citation/30177863/full_citation DB - PRIME DP - Unbound Medicine ER -
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