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

Novo Nordisk Foundation Center for Basic Metabolic Research
University of Copenhagen
University of Copenhagen
Southern Denmark University
University of Greenland
Wellcome Sanger Institute
Harokopio University
Steno Diabetes Center Copenhagen
Faculty of Health Sciences, University of Southern Denmark

Research output: Contribution to journal › Article › peer-review

161 Scopus citations

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
Pages (from-to)	172-174
Number of pages	3
Journal	Nature Genetics
Volume	50
Issue number	2
DOIs	https://doi.org/10.1038/s41588-017-0022-7
State	Published - 1 Feb 2018
Externally published	Yes

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SDG 3 Good Health and Well-being

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10.1038/s41588-017-0022-7

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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(2), 172-174. https://doi.org/10.1038/s41588-017-0022-7

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title = "Loss-of-function variants in ADCY3 increase risk of obesity and type 2 diabetes",

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.",

author = "Niels Grarup and Ida Moltke and Andersen, \{Mette K.\} and Maria Dalby and Kristoffer Vitting-Seerup and Timo Kern and Yuvaraj Mahendran and Emil J{\o}rsboe and Larsen, \{Christina V.L.\} and Dahl-Petersen, \{Inger K.\} and Arthur Gilly and Daniel Suveges and George Dedoussis and Eleftheria Zeggini and Oluf Pedersen and Robin Andersson and Peter Bjerregaard and J{\o}rgensen, \{Marit E.\} and Anders Albrechtsen and Torben Hansen",

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doi = "10.1038/s41588-017-0022-7",

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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, no. 2, pp. 172-174. https://doi.org/10.1038/s41588-017-0022-7

TY - JOUR

T1 - Loss-of-function variants in ADCY3 increase risk of obesity and type 2 diabetes

AU - Grarup, Niels

AU - Moltke, Ida

AU - Andersen, Mette K.

AU - Dalby, Maria

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

PY - 2018/2/1

Y1 - 2018/2/1

N2 - 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.

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.

UR - https://www.scopus.com/pages/publications/85041512437

U2 - 10.1038/s41588-017-0022-7

DO - 10.1038/s41588-017-0022-7

M3 - Article

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AN - SCOPUS:85041512437

SN - 1061-4036

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SP - 172

EP - 174

JO - Nature Genetics

JF - Nature Genetics

IS - 2

ER -

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

Abstract

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