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Genes Immun. 2019 Apr;20(4):281-292. doi: 10.1038/s41435-018-0034-z. Epub 2018 Jun 8.

Genetic variants at the 16p13 locus confer risk for eosinophilic esophagitis.

Author information

1
Department of Pediatrics, Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.
2
Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Division of Allergy and Immunology, University of Cincinnati, Cincinnati, OH, USA.
3
Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.
4
Pediatric Allergy and Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
5
Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
6
Department of Pediatrics, Pediatric Allergy and Immunology, Johns Hopkins University School of Medicine, Baltimore, USA.
7
Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
8
Department of Allergy and Immunology, Arkansas Children's Hospital, Little Rock, AR, USA.
9
Department of Pediatrics, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
10
Department of Pediatrics and Digestive Health Institute, Section of Pediatric Gastroenterology, Hepatology and Nutrition, Gastrointestinal Eosinophilic Diseases Program, Children's Hospital Colorado, Aurora, CO, USA.
11
Department of Medicine, Mucosal Inflammation Program, University of Colorado School of Medicine, Aurora, CO, USA.
12
EMMES Corporation, Rockville, MD, USA.
13
Department of Pediatrics, Icahn School of Medicine at Mount Sinai, The Elliot and Roslyn Jaffe Food Allergy Institute, Division of Allergy and Immunology, Kravis Children's Hospital, New York, NY, USA.
14
Department of Pediatrics, Division of Human Genetics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.
15
Arthritis and Clinical Immunology Program, Division of Genomics and Data Sciences, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
16
Departments of Medicine, Schools of Medicine, The University of Alabama, Birmingham, AL, USA.
17
United States Department of Veterans Affairs Medical Center, Cincinnati, OH, USA.
18
Department of Pediatrics, Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA. leah.kottyan@cchmc.org.
19
United States Department of Veterans Affairs Medical Center, Cincinnati, OH, USA. leah.kottyan@cchmc.org.
20
Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Division of Allergy and Immunology, University of Cincinnati, Cincinnati, OH, USA. marc.rothenberg@cchmc.org.

Abstract

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus triggered by immune hypersensitivity to food. Herein, we tested whether genetic risk factors for known, non-allergic, immune-mediated diseases, particularly those involving autoimmunity, were associated with EoE risk. We used the high-density Immunochip platform, encoding 200,000 genetic variants for major auto-immune disease. Accordingly, 1214 subjects with EoE of European ancestry and 3734 population controls were genotyped and assessed using data directly generated or imputed from the previously published GWAS. We found lack of association of EoE with the genetic variants in the major histocompatibility complex (MHC) class I, II, and III genes and nearly all other loci using a highly powered study design with dense genotyping throughout the locus. Importantly, we identified an EoE risk locus at 16p13 with genome-wide significance (Pcombined=2.05 × 10-9, odds ratio = 0.76-0.81). This region is known to encode for the genes CLEC16A, DEXI, and CIITI, which are expressed in immune cells and esophageal epithelial cells. Suggestive EoE risk were also seen 5q23 (intergenic) and 7p15 (JAZF1). Overall, we have identified an additional EoE risk locus at 16p13 and highlight a shared and unique genetic etiology of EoE with a spectrum of immune-associated diseases.

PMID:
29904099
PMCID:
PMC6286696
DOI:
10.1038/s41435-018-0034-z
[Indexed for MEDLINE]
Free PMC Article

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