A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease
Scott RA., Freitag DF., Li L., Chu AY., Surendran P., Young R., Grarup N., Stancáková A., Chen Y., Varga TV., Yaghootkar H., Luan J., Zhao JH., Willems SM., Wessel J., Wang S., Maruthur N., Michailidou K., Pirie A., van der Lee SJ., Gillson C., Al Olama AA., Amouyel P., Arriola L., Arveiler D., Aviles-Olmos I., Balkau B., Barricarte A., Barroso I., Garcia SB., Bis JC., Blankenberg S., Boehnke M., Boeing H., Boerwinkle E., Borecki IB., Bork-Jensen J., Bowden S., Caldas C., Caslake M., Cupples LA., Cruchaga C., Czajkowski J., den Hoed M., Dunn JA., Earl HM., Ehret GB., Ferrannini E., Ferrieres J., Foltynie T., Ford I., Forouhi NG., Gianfagna F., Gonzalez C., Grioni S., Hiller L., Jansson J-H., Jørgensen ME., Jukema JW., Kaaks R., Kee F., Kerrison ND., Key TJ., Kontto J., Kote-Jarai Z., Kraja AT., Kuulasmaa K., Kuusisto J., Linneberg A., Liu C., Marenne G., Mohlke KL., Morris AP., Muir K., Müller-Nurasyid M., Munroe PB., Navarro C., Nielsen SF., Nilsson PM., Nordestgaard BG., Packard CJ., Palli D., Panico S., Peloso GM., Perola M., Peters A., Poole CJ., Quirós JR., Rolandsson O., Sacerdote C., Salomaa V., Sánchez M-J., Sattar N., Sharp SJ., Sims R., Slimani N., Smith JA., Thompson DJ., Trompet S., Tumino R., van der A DL., van der Schouw YT., Virtamo J., Walker M., Walter K., Abraham JE., Amundadottir LT., Aponte JL., Butterworth AS., Dupuis J., Easton DF., Eeles RA., Erdmann J., Franks PW., Frayling TM., Hansen T., Howson JMM., Jørgensen T., Kooner J., Laakso M., Langenberg C., McCarthy MI., Pankow JS., Pedersen O., Riboli E., Rotter JI., Saleheen D., Samani NJ., Schunkert H., Vollenweider P., O’Rahilly S., Deloukas P., Danesh J., Goodarzi MO., Kathiresan S., Meigs JB., Ehm MG., Wareham NJ., Waterworth DM.
A missense variant in GLP1R associated with lower fasting glucose levels and protective against T2D is associated with lower risk of coronary heart disease, suggesting that GLP1R agonists are not associated with an unacceptable increase in cardiovascular risk.