Loss-of-function variants in ADCY3 increase risk of obesity and type 2 diabetes.
["Grarup, Niels", "Moltke, Ida", "Andersen, Mette K", "Dalby, Maria", "Vitting-Seerup, Kristoffer", "Kern, Timo", "Mahendran, Yuvaraj", "J\u00f8rsboe, Emil", "Larsen, Christina V L", "Dahl-Petersen, Inger K", "Gilly, Arthur", "Suveges, Daniel", "Dedoussis, George", "Zeggini, Eleftheria", "Pedersen, Oluf", "Andersson, Robin", "Bjerregaard, Peter", "J\u00f8rgensen, Marit E", "Albrechtsen, Anders", "Hansen, Torben"]
Nature genetics 2018
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.