Research ArticleCardiovascular Genomics

A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease

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Science Translational Medicine  01 Jun 2016:
Vol. 8, Issue 341, pp. 341ra76
DOI: 10.1126/scitranslmed.aad3744

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At risk by association

Genetics could soon routinely tell clinicians whether certain drugs are putting patients at risk of developing heart disease or cancer. Scott et al. looked at six genes that encode the targets of various drugs for type 2 diabetes or obesity, to see whether any genetic variations were linked to metabolic traits like body mass index and fasting glucose levels. Using several cohorts totaling more than 50,000 individuals, they landed on one particular variant in GLP1R—the gene encoding glucagon-like peptide-1 receptor, which is the target for certain glucose-lowering drugs frequently used in the clinic, like exenatide and liraglutide—associated with fasting glucose. The authors then compared this variant against disease outcomes, like coronary heart disease (CHD). In more than 200,000 individuals—some with heart disease, some as controls—the GLPR1 variant was actually protective against CHD, rather than causing any additional risk, and was not associated with various cancers or neurological diseases.

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