作者
Nicholas Bowker, Robert Hansford, Stephen Burgess, Christopher N Foley, Victoria PW Auyeung, A Mesut Erzurumluoglu, Isobel D Stewart, Eleanor Wheeler, Maik Pietzner, Fiona Gribble, Frank Reimann, Pallav Bhatnagar, Matthew P Coghlan, Nicholas J Wareham, Claudia Langenberg
发表日期
2021/11/1
期刊
Diabetes
卷号
70
期号
11
页码范围
2706-2719
出版商
American Diabetes Association
简介
There is considerable interest in GIPR agonism to enhance the insulinotropic and extrapancreatic effects of GIP, thereby improving glycemic and weight control in type 2 diabetes (T2D) and obesity. Recent genetic epidemiological evidence has implicated higher GIPR-mediated GIP levels in raising coronary artery disease (CAD) risk, a potential safety concern for GIPR agonism. We therefore aimed to quantitatively assess whether the association between higher GIPR-mediated fasting GIP levels and CAD risk is mediated via GIPR or is instead the result of linkage disequilibrium (LD) confounding between variants at the GIPR locus. Using Bayesian multitrait colocalization, we identified a GIPR missense variant, rs1800437 (G allele; E354), as the putatively causal variant shared among fasting GIP levels, glycemic traits, and adiposity-related traits (posterior probability for colocalization [PPcoloc] > 0.97; PP explained …
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