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

Grarup N., Moltke I., Andersen MK., Dalby M., Vitting-Seerup K., Kern T., Mahendran Y., Jørsboe E., Larsen CVL., Dahl-Petersen IK., Gilly A., Suveges D., Dedoussis G., Zeggini E., Pedersen O., Andersson R., Bjerregaard P., Jørgensen ME., Albrechtsen A., Hansen T.

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.

DOI

10.1038/s41588-017-0022-7

Type

Journal article

Publication Date

2018-02-01T00:00:00+00:00

Volume

50

Pages

172 - 174

Total pages

2

Addresses

Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Keywords

Humans, Diabetes Mellitus, Type 2, Obesity, Genetic Predisposition to Disease, Risk Factors, Case-Control Studies, Cohort Studies, Gene Frequency, Genotype, Adult, Aged, Aged, 80 and over, Middle Aged, Greenland, Female, Male, Genome-Wide Association Study, Young Adult, Adenylyl Cyclases, Loss of Function Mutation, Inuit

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