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

96 Citationer (Scopus)

Abstrakt

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.

Originalsprog	Engelsk
Tidsskrift	Nature Genetics
Vol/bind	50
Sider (fra-til)	172-174
Antal sider	2
ISSN	1061-4036
DOI	https://doi.org/10.1038/s41588-017-0022-7
Status	Udgivet - jan. 2018

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10.1038/s41588-017-0022-7

Citationsformater

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, bind 50, s. 172-174. https://doi.org/10.1038/s41588-017-0022-7

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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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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",

year = "2018",

month = jan,

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

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pages = "172--174",

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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 - 2018/1

Y1 - 2018/1

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.

KW - Journal Article

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DO - 10.1038/s41588-017-0022-7

M3 - Journal article

C2 - 29311636

VL - 50

SP - 172

EP - 174

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

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

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