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
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenylyl Cyclases / genetics*
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Adult
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Aged
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Aged, 80 and over
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Case-Control Studies
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Cohort Studies
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Diabetes Mellitus, Type 2 / complications
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Diabetes Mellitus, Type 2 / epidemiology
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Diabetes Mellitus, Type 2 / genetics*
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Female
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Gene Frequency
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Genetic Predisposition to Disease
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Genome-Wide Association Study
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Genotype
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Greenland / epidemiology
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Humans
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Inuit / genetics
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Inuit / statistics & numerical data
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Loss of Function Mutation*
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Male
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Middle Aged
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Obesity / complications
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Obesity / epidemiology
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Obesity / genetics*
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Risk Factors
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Young Adult
Substances
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Adenylyl Cyclases
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adenylate cyclase 3