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

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 enrich...

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Veröffentlicht in:	Nature genetics 2018-02, Vol.50 (2), p.172-174
Hauptverfasser:	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
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Sprache:	eng
Schlagworte:	38/43 38/91 45/23 631/208/205 631/443 692/699/2743 Adenylate cyclase Adenylyl Cyclases - genetics Adult Aged Aged, 80 and over Agriculture Animal Genetics and Genomics Bioinformatics Biomedical and Life Sciences Biomedicine Body mass index Brief Communication Cancer Research Case-Control Studies Cohort Studies Diabetes Diabetes mellitus Diabetes mellitus (non-insulin dependent) Diabetes Mellitus, Type 2 - complications Diabetes Mellitus, Type 2 - epidemiology Diabetes Mellitus, Type 2 - genetics Etiology Female Gene expression Gene Frequency Gene Function Genetic Predisposition to Disease Genome-Wide Association Study Genomes Genotype Genotype & phenotype Greenland - epidemiology Human Genetics Humans Inuit Inuit - genetics Inuit - statistics & numerical data Life sciences Loss of Function Mutation Male Middle Aged Obesity Obesity - complications Obesity - epidemiology Obesity - genetics Population Ribonucleic acid Risk Factors RNA Young Adult
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container_title	Nature genetics
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creator	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
description	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. Individuals from a Greenlandic Inuit population with homozygous loss-of-function variants in ADCY3 (adenylate cyclase 3) have increased risk for obesity and type 2 diabetes. Carriers of rare ADCY3 variants in trans-ancestry populations also show increased association with type 2 diabetes.
doi_str_mv	10.1038/s41588-017-0022-7
format	Article
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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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c536t-a7b2414ca27dfbe0d789ff001d53170d2242b18bddaeb57255f58ce2a5efdb5e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>38/43</topic><topic>38/91</topic><topic>45/23</topic><topic>631/208/205</topic><topic>631/443</topic><topic>692/699/2743</topic><topic>Adenylate cyclase</topic><topic>Adenylyl Cyclases - genetics</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Agriculture</topic><topic>Animal Genetics and Genomics</topic><topic>Bioinformatics</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Body mass index</topic><topic>Brief Communication</topic><topic>Cancer Research</topic><topic>Case-Control Studies</topic><topic>Cohort Studies</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>Diabetes Mellitus, Type 2 - complications</topic><topic>Diabetes Mellitus, Type 2 - epidemiology</topic><topic>Diabetes Mellitus, Type 2 - genetics</topic><topic>Etiology</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Frequency</topic><topic>Gene Function</topic><topic>Genetic Predisposition to Disease</topic><topic>Genome-Wide Association Study</topic><topic>Genomes</topic><topic>Genotype</topic><topic>Genotype & phenotype</topic><topic>Greenland - epidemiology</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Inuit</topic><topic>Inuit - genetics</topic><topic>Inuit - statistics & numerical data</topic><topic>Life sciences</topic><topic>Loss of Function Mutation</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Obesity</topic><topic>Obesity - complications</topic><topic>Obesity - epidemiology</topic><topic>Obesity - genetics</topic><topic>Population</topic><topic>Ribonucleic acid</topic><topic>Risk Factors</topic><topic>RNA</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Grarup, Niels</creatorcontrib><creatorcontrib>Moltke, Ida</creatorcontrib><creatorcontrib>Andersen, Mette K.</creatorcontrib><creatorcontrib>Dalby, Maria</creatorcontrib><creatorcontrib>Vitting-Seerup, Kristoffer</creatorcontrib><creatorcontrib>Kern, Timo</creatorcontrib><creatorcontrib>Mahendran, Yuvaraj</creatorcontrib><creatorcontrib>Jørsboe, Emil</creatorcontrib><creatorcontrib>Larsen, Christina V. 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recordid	cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5828106
source	MEDLINE; Springer Nature - Complete Springer Journals; Nature Journals Online
subjects	38/43 38/91 45/23 631/208/205 631/443 692/699/2743 Adenylate cyclase Adenylyl Cyclases - genetics Adult Aged Aged, 80 and over Agriculture Animal Genetics and Genomics Bioinformatics Biomedical and Life Sciences Biomedicine Body mass index Brief Communication Cancer Research Case-Control Studies Cohort Studies Diabetes Diabetes mellitus Diabetes mellitus (non-insulin dependent) Diabetes Mellitus, Type 2 - complications Diabetes Mellitus, Type 2 - epidemiology Diabetes Mellitus, Type 2 - genetics Etiology Female Gene expression Gene Frequency Gene Function Genetic Predisposition to Disease Genome-Wide Association Study Genomes Genotype Genotype & phenotype Greenland - epidemiology Human Genetics Humans Inuit Inuit - genetics Inuit - statistics & numerical data Life sciences Loss of Function Mutation Male Middle Aged Obesity Obesity - complications Obesity - epidemiology Obesity - genetics Population Ribonucleic acid Risk Factors RNA Young Adult
title	Loss-of-function variants in ADCY3 increase risk of obesity and type 2 diabetes
url	https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-31T17%3A48%3A46IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Loss-of-function%20variants%20in%20ADCY3%20increase%20risk%20of%20obesity%20and%20type%202%20diabetes&rft.jtitle=Nature%20genetics&rft.au=Grarup,%20Niels&rft.date=2018-02-01&rft.volume=50&rft.issue=2&rft.spage=172&rft.epage=174&rft.pages=172-174&rft.issn=1061-4036&rft.eissn=1546-1718&rft_id=info:doi/10.1038/s41588-017-0022-7&rft_dat=%3Cproquest_pubme%3E2133373868%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2133373868&rft_id=info:pmid/29311636&rfr_iscdi=true