Rare heterozygous loss-of-function variants in the human GLP-1 receptor do not associate with cardiometabolic phenotypes.

Josefine U Melchiorsen,Kimmie V Sørensen,Jette Bork-Jensen,Hüsün S Kizilkaya,Lærke S Gasbjerg,Alexander S Hauser,Jørgen Rungby,Henrik T Sørensen,Allan Vaag,Jens S Nielsen, Oluf Pedersen,Allan Linneberg,Bolette Hartmann,Anette P Gjesing,Jens J Holst,Torben Hansen,Mette M Rosenkilde,Niels Grarup

The Journal of clinical endocrinology and metabolism（2023）

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摘要

Since no homozygous LoS nor pLoF variants were identified and heterozygous carriers had similar cardiometabolic phenotype as non-carriers, we conclude that GLP-1R may be of particular importance in human physiology, due to a potential evolutionary intolerance of harmful homozygous GLP1R variants.

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关键词

functional study, genetic association, GLP-1R, glucagon-like peptide 1 receptor, type 2 diabetes

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