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

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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 languageEnglish
JournalNature Genetics
Volume50
Issue number2
Pages (from-to)172–174
ISSN1061-4036
DOIs
Publication statusPublished - Feb 2018

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Type 2 Diabetes Mellitus
RNA Splice Sites
RNA
Population
adenylate cyclase 3

Keywords

  • Journal Article

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Grarup, N., Moltke, I., Andersen, M. K., Dalby, M., Vitting-Seerup, K., Kern, T., ... 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
Grarup, Niels ; Moltke, Ida ; Andersen, Mette K ; Dalby, Maria ; Vitting-Seerup, Kristoffer ; Kern, Timo ; Mahendran, Yuvaraj ; Jørsboe, Emil ; Larsen, Christina V L ; Dahl-Petersen, Inger K ; Gilly, Arthur ; Suveges, Daniel ; Dedoussis, George ; Zeggini, Eleftheria ; Pedersen, Oluf ; Andersson, Robin ; Bjerregaard, Peter ; Jørgensen, Marit E ; Albrechtsen, Anders ; Hansen, Torben. / Loss-of-function variants in ADCY3 increase risk of obesity and type 2 diabetes. In: Nature Genetics. 2018 ; Vol. 50, No. 2. pp. 172–174.
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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.",
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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

Loss-of-function variants in ADCY3 increase risk of obesity and type 2 diabetes. / Grarup, Niels; Moltke, Ida; Andersen, Mette K; Dalby, Maria; Vitting-Seerup, Kristoffer; Kern, Timo; Mahendran, Yuvaraj; Jørsboe, Emil; Larsen, Christina V L; Dahl-Petersen, Inger K; Gilly, Arthur; Suveges, Daniel; Dedoussis, George; Zeggini, Eleftheria; Pedersen, Oluf; Andersson, Robin; Bjerregaard, Peter; Jørgensen, Marit E; Albrechtsen, Anders; Hansen, Torben.

In: Nature Genetics, Vol. 50, No. 2, 02.2018, p. 172–174.

Research output: Contribution to journalLetterResearchpeer-review

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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

Y1 - 2018/2

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.

KW - Journal Article

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DO - 10.1038/s41588-017-0022-7

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SP - 172

EP - 174

JO - Nature Genetics

JF - Nature Genetics

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Grarup N, Moltke I, Andersen MK, Dalby M, Vitting-Seerup K, Kern T et al. Loss-of-function variants in ADCY3 increase risk of obesity and type 2 diabetes. Nature Genetics. 2018 Feb;50(2):172–174. https://doi.org/10.1038/s41588-017-0022-7