Loss-of-function variants in ADCY3 increase risk of obesity and type 2 diabetes

We have identified a variant in ADCY3 (encoding adenylate cyclase 3) associated with markedly increased risk of obesity and type 2 diabetes in the Greenlandic population. The variant disrupts a splice acceptor site, and carriers have decreased ADCY3 RNA expression. Additionally, we observe an enrich...

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Veröffentlicht in:Nature genetics 2018-02, Vol.50 (2), p.172-174
Hauptverfasser: Grarup, Niels, Moltke, Ida, Andersen, Mette K., Dalby, Maria, Vitting-Seerup, Kristoffer, Kern, Timo, Mahendran, Yuvaraj, Jørsboe, Emil, Larsen, Christina V. L., Dahl-Petersen, Inger K., Gilly, Arthur, Suveges, Daniel, Dedoussis, George, Zeggini, Eleftheria, Pedersen, Oluf, Andersson, Robin, Bjerregaard, Peter, Jørgensen, Marit E., Albrechtsen, Anders, Hansen, Torben
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Sprache:eng
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Zusammenfassung:We have identified a variant in ADCY3 (encoding adenylate cyclase 3) associated with markedly increased risk of obesity and type 2 diabetes in the Greenlandic population. The variant disrupts a splice acceptor site, and carriers have decreased ADCY3 RNA expression. Additionally, we observe an enrichment of rare ADCY3 loss-of-function variants among individuals with type 2 diabetes in trans-ancestry cohorts. These findings provide new information on disease etiology relevant for future treatment strategies. Individuals from a Greenlandic Inuit population with homozygous loss-of-function variants in ADCY3 (adenylate cyclase 3) have increased risk for obesity and type 2 diabetes. Carriers of rare ADCY3 variants in trans-ancestry populations also show increased association with type 2 diabetes.
ISSN:1061-4036
1546-1718
DOI:10.1038/s41588-017-0022-7