Independent Genetic Effects of Glucagon-like Peptide-1 Receptor Locus on Body Mass Index and Type 2 Diabetes

Background: locus in both body mass index (BMI) and T2D, but it remains unclear whether their underlying genetic associations are the same. Methods: locus for BMI and T2D. Results: ). Both variants were associated with higher T2D risk, but with distinct patterns after BMI adjustment: the rs12213929-T2D association persisted after adjustment for BMI (OR = 1.02; 95% CI 1.01-1.03; p = 0.0004), whereas the rs13216992-T2D association was fully attenuated (OR = 1.00; 95% CI 0.99-1.01; p = 0.68). Fine-mapping identified a compact 95% BMI credible set of 17 variants and a broader 95% T2D credible set of 42 variants, with all BMI credible variants contained within the T2D set. Conclusions: variation can inform precision prevention and treatment of obesity and T2D.

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Publication Details

Journal
medRxiv
Published
2026-04-13
DOI
https://doi.org/10.64898/2026.04.10.26350615
Primary Topic
Diabetes Treatment and Management
Type
article
Field-Weighted Citation Impact
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article

Independent Genetic Effects of Glucagon-like Peptide-1 Receptor Locus on Body Mass Index and Type 2 Diabetes

Peter D. Reaven, the VA Million Veteran Program, Gregorio V. Linchangco, Luc Djoussé et al.
medRxiv
Diabetes Treatment and Management
article

Independent Genetic Effects of Glucagon-like Peptide-1 Receptor Locus on Body Mass Index and Type 2 Diabetes

Peter D. Reaven, the VA Million Veteran Program, Gregorio V. Linchangco, Luc Djoussé, Yan V. Sun, Jacob Joseph, Mary K. Rhee, Amonae Dabbs‐Brown, Jin J Zhou, Chang Liu, Peter WF Wilson, Kelly Cho, J. Michael Gaziano, Qin Hui, Lawrence S Phillips
article en

Abstract

Background: locus in both body mass index (BMI) and T2D, but it remains unclear whether their underlying genetic associations are the same. Methods: locus for BMI and T2D. Results: ). Both variants were associated with higher T2D risk, but with distinct patterns after BMI adjustment: the rs12213929-T2D association persisted after adjustment for BMI (OR = 1.02; 95% CI 1.01-1.03; p = 0.0004), whereas the rs13216992-T2D association was fully attenuated (OR = 1.00; 95% CI 0.99-1.01; p = 0.68). Fine-mapping identified a compact 95% BMI credible set of 17 variants and a broader 95% T2D credible set of 42 variants, with all BMI credible variants contained within the T2D set. Conclusions: variation can inform precision prevention and treatment of obesity and T2D.

medRxiv
Brigham and Women's Hospital (US), Harvard University (US), Emory University (US), University of Phoenix (US), Brown University (US), UCLA Health (US), VA Boston Healthcare System (US), Providence VA Medical Center (US), Atlanta VA Health Care System (US), Phoenix College (US)
Good health and well-being
Openalex Percentile: Top 22%
Diabetes Treatment and Management
DOIOpen Access PDFOpenAlex
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