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

Nat Genet. 2018 Feb;50(2):172-174. doi: 10.1038/s41588-017-0022-7. Epub 2018 Jan 8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclases / genetics*
  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genotype
  • Greenland / epidemiology
  • Humans
  • Inuits / genetics
  • Inuits / statistics & numerical data
  • Loss of Function Mutation*
  • Male
  • Middle Aged
  • Obesity / complications
  • Obesity / epidemiology
  • Obesity / genetics*
  • Risk Factors
  • Young Adult

Substances

  • Adenylyl Cyclases
  • adenylate cyclase 3