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

Niels Grarup; Ida Moltke; Mette K Andersen; Maria Dalby; Kristoffer Vitting-Seerup; Timo Kern; Yuvaraj Mahendran; Emil Jørsboe; Christina V L Larsen; Inger K Dahl-Petersen; Arthur Gilly; Daniel Suveges; George Dedoussis; Eleftheria Zeggini; Oluf Pedersen; Robin Andersson; Peter Bjerregaard; Marit E Jørgensen; Anders Albrechtsen; Torben Hansen

doi:10.1038/s41588-017-0022-7

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

Niels Grarup, Ida Moltke, Mette K Andersen, Maria Dalby, Kristoffer Vitting-Seerup, Timo Kern, Yuvaraj Mahendran, Emil Jørsboe, Christina V L Larsen, Inger K Dahl-Petersen, Arthur Gilly, Daniel Suveges, George Dedoussis, Eleftheria Zeggini, Oluf Pedersen, Robin Andersson, Peter Bjerregaard, Marit E Jørgensen, Anders Albrechtsen, Torben Hansen

Steno Diabetes Center Copenhagen

103 Citations (Scopus)

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.

Original language	English
Journal	Nature Genetics
Volume	50
Pages (from-to)	172-174
Number of pages	2
ISSN	1061-4036
DOIs	https://doi.org/10.1038/s41588-017-0022-7
Publication status	Published - Jan 2018

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Grarup, N., Moltke, I., Andersen, M. K., Dalby, M., Vitting-Seerup, K., Kern, T., Mahendran, Y., Jørsboe, E., Larsen, C. V. L., Dahl-Petersen, I. K., Gilly, A., Suveges, D., Dedoussis, G., Zeggini, E., Pedersen, O., Andersson, R., Bjerregaard, P., Jørgensen, M. E., Albrechtsen, A., & Hansen, T. (2018). Loss-of-function variants in ADCY3 increase risk of obesity and type 2 diabetes. Nature Genetics, 50, 172-174. https://doi.org/10.1038/s41588-017-0022-7

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 2018, 'Loss-of-function variants in ADCY3 increase risk of obesity and type 2 diabetes', Nature Genetics, vol. 50, pp. 172-174. https://doi.org/10.1038/s41588-017-0022-7

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AU - Vitting-Seerup, Kristoffer

AU - Kern, Timo

AU - Mahendran, Yuvaraj

AU - Jørsboe, Emil

AU - Larsen, Christina V L

AU - Dahl-Petersen, Inger K

AU - Gilly, Arthur

AU - Suveges, Daniel

AU - Dedoussis, George

AU - Zeggini, Eleftheria

AU - Pedersen, Oluf

AU - Andersson, Robin

AU - Bjerregaard, Peter

AU - Jørgensen, Marit E

AU - Albrechtsen, Anders

AU - Hansen, Torben

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AB - 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.

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

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