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

ABSTRACT: Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to guide development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in six genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing and follow-up in 39,979 individuals by targeted genotyping, with additional in silico follow-up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested th

SUBMITTER: Scott RA 

PROVIDER: S-EPMC5219001 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature