Shared genetic etiology of obesity-related traits and Barrett's esophagus/adenocarcinoma: Insights from genome-wide association studies

Bohmer AC, Hecker J, Schroder J, Gharahkhani P, May A, Gerges C, Anders M, Becker J, Hess T, Kreuser N, Thieme R, Noder T, Venerito M, Veits L, Schmidt T, Fuchs C, Izbicki JR, Holscher AH, Dietrich A, Moulla Y, Lyros O, Lang H, Lorenz D, Schumacher B, Mayershofer R, Vashist Y, Ott K, Vieth M, Weismuller J, Moebus S, Knapp M, Neuhaus H, Rosch T, Ell C, Nothen MM, Whiteman DC, Tomlinson I, Jankowski J, Fitzgerald RC, Palles C, Vaughan TL, Gockel I, Thrift AP, Fier H, Schumacher J (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Book Volume: 29

Pages Range: 427-433

Journal Issue: 2

DOI: 10.1158/1055-9965.EPI-19-0374

Abstract

Background: Obesity is amajor risk factor for esophageal adenocarcinoma (EA) and its precursor Barrett's esophagus (BE). Research suggests that individuals with high genetic risk to obesity have a higher BE/EArisk.To facilitate understanding of biological factors that lead to progression from BE to EA, the present study investigated the shared genetic background of BE/EA and obesity-related traits. Methods: Cross-trait linkage disequilibrium score regression was applied to summary statistics from genome-wide association metaanalyses on BE/EA and on obesity traits. Body mass index (BMI) was used as a proxy for general obesity, and waist-to-hip ratio (WHR) for abdominal obesity. For single marker analyses, all genome-wide significant risk alleles for BMI and WHR were compared with summary statistics of the BE/EA meta-analyses. Results: Sex-combined analyses revealed a significant genetic correlation between BMI and BE/EA (rg = 0.13, P = 2 x 10^-04) and a rg of 0.12 between WHR and BE/EA (P = 1 × 10^-02). Sexspecific analyses revealed a pronounced genetic correlation between BMI and EA in females (rg = 0.17, P = 1.2 × 10^-03), and WHR and EA in males (rg = 0.18, P = 1.51 × 10^-02). On the single marker level, significant enrichment of concordant effects was observed for BMI and BE/EA risk variants (P = 8.45 × 10^-03) and WHR and BE/EA risk variants (P = 2 × 10^-02). Conclusions: Our study provides evidence for sex-specific genetic correlations that might reflect specific biological mechanisms. The data demonstrate that shared genetic factors are particularly relevant in progression from BE to EA. Impact: Our study quantifies the genetic correlation between BE/EA and obesity. Further research is now warranted to elucidate these effects and to understand the shared pathophysiology.

Authors with CRIS profile

Involved external institutions

Rheinische Friedrich-Wilhelms-Universität Bonn Germany (DE) Harvard T.H. Chan School of Public Health United States (USA) (US) Wellcome Centre for Human Genetics United Kingdom (GB) Baylor College of Medicine United States (USA) (US) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) Sana Kliniken AG Germany (DE) Evangelisches Krankenhaus Düsseldorf Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Universitätsklinikum Gießen und Marburg (UKGM) Germany (DE) Universitätsklinikum Leipzig Germany (DE) Otto-von-Guericke-Universität Magdeburg Germany (DE) Klinikum Bayreuth Germany (DE) Ruprecht-Karls-Universität Heidelberg Germany (DE) Universität zu Köln Germany (DE) Johannes Gutenberg-Universität Mainz (JGU) Germany (DE) Klinikum Darmstadt Germany (DE) Elisabeth-Krankenhaus Essen Germany (DE) Universität Duisburg-Essen (UDE) Germany (DE) University of Central Lancashire (UCLan) United Kingdom (GB) University of Cambridge United Kingdom (GB) Fred Hutchinson Cancer Research Center United States (USA) (US)

How to cite

APA:

Bohmer, A.C., Hecker, J., Schroder, J., Gharahkhani, P., May, A., Gerges, C.,... Schumacher, J. (2020). Shared genetic etiology of obesity-related traits and Barrett's esophagus/adenocarcinoma: Insights from genome-wide association studies. Cancer Epidemiology Biomarkers & Prevention, 29(2), 427-433. https://doi.org/10.1158/1055-9965.EPI-19-0374

MLA:

Bohmer, Anne C., et al. "Shared genetic etiology of obesity-related traits and Barrett's esophagus/adenocarcinoma: Insights from genome-wide association studies." Cancer Epidemiology Biomarkers & Prevention 29.2 (2020): 427-433.

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