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 Laerke Smidt Gasbjerg Alexander Sebastian HauserJørgen RungbyHenrik T SørensenAllan Arthur VaagJens S NielsenOluf Pedersen Allan Linneberg Bolette Hartmann Anette Prior Gjesing Jens Juul Holst Torben Hansen Mette Marie Rosenkilde Niels Grarup

Published in: The Journal of clinical endocrinology and metabolism (2023)

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.

Keyphrases

endothelial cells
copy number
early onset
induced pluripotent stem cells
pluripotent stem cells
genome wide
dna methylation
binding protein