Replication and extension of genome-wide association study results for obesity in 4,923 adults from Northern Sweden
Recent genome-wide association studies (GWAS) have identified multiple risk loci for common obesity ( FTO, MC4R, TMEM18, GNPDA2, SH2B1, KCTD15, MTCH2, NEGR1 , and PCSK1 ). Here we extend those studies by examining associations with adiposity and type 2 diabetes in Swedish adults. The nine single nuc...
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fthighwire:oai:open-archive.highwire.org:hmg:ddp041v1 2023-05-15T17:44:54+02:00 Replication and extension of genome-wide association study results for obesity in 4,923 adults from Northern Sweden Renström, Frida Payne, Felicity Nordström, Anna Brito, Ema C. GIANT Consortium, Rolandsson, Olov Hallmans, Göran Barroso, Ines Nordström, Peter Franks, Paul W. 2009-01-22 02:56:27.0 text/html http://hmg.oxfordjournals.org/cgi/content/short/ddp041v1 https://doi.org/10.1093/hmg/ddp041 en eng Oxford University Press http://hmg.oxfordjournals.org/cgi/content/short/ddp041v1 http://dx.doi.org/10.1093/hmg/ddp041 Copyright (C) 2009, Oxford University Press Article TEXT 2009 fthighwire https://doi.org/10.1093/hmg/ddp041 2013-05-27T20:54:20Z Recent genome-wide association studies (GWAS) have identified multiple risk loci for common obesity ( FTO, MC4R, TMEM18, GNPDA2, SH2B1, KCTD15, MTCH2, NEGR1 , and PCSK1 ). Here we extend those studies by examining associations with adiposity and type 2 diabetes in Swedish adults. The nine single nucleotide polymorphisms (SNPs) were genotyped in 3,885 non-diabetic and 1,038 diabetic individuals with available measures of height, weight and BMI. Adipose mass and distribution was objectively assessed using dual energy X-ray absorptiometry (DEXA) in a sub-group of non-diabetics (n=2,206). In models with adipose mass traits, BMI or obesity as outcomes, the most strongly associated SNP was FTO rs1121980 ( P <0.001). Five other SNPs ( SH2B1 rs7498665, MTCH2 rs4752856, MC4R rs17782313, NEGR1 rs2815752, and GNPDA2 rs10938397) were significantly associated with obesity. To summarize the overall genetic burden, a weighted risk score comprising a subset of SNPs was constructed; those in the top quintile of the score were heavier (+2.6kg) and had more total (+2.4kg), gynoid (+191g), and abdominal (+136g) adipose tissue than those in the lowest quintile (all P <0.001). The genetic burden score significantly increased diabetes risk, with those in the highest quintile (n=193/594 cases/controls) being at 1.55-fold (95% CI: 1.21-1.99; P <0.0001) greater risk of type 2 diabetes than those in the lowest quintile (n=130/655 cases/controls). In summary, we have statistically replicated six of the previously associated obese-risk loci and our results suggest that the weight-inducing effects of these variants are explained largely by increased adipose accumulation. Text Northern Sweden HighWire Press (Stanford University) Human Molecular Genetics 18 8 1489 1496 |
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Article Renström, Frida Payne, Felicity Nordström, Anna Brito, Ema C. GIANT Consortium, Rolandsson, Olov Hallmans, Göran Barroso, Ines Nordström, Peter Franks, Paul W. Replication and extension of genome-wide association study results for obesity in 4,923 adults from Northern Sweden |
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Article |
description |
Recent genome-wide association studies (GWAS) have identified multiple risk loci for common obesity ( FTO, MC4R, TMEM18, GNPDA2, SH2B1, KCTD15, MTCH2, NEGR1 , and PCSK1 ). Here we extend those studies by examining associations with adiposity and type 2 diabetes in Swedish adults. The nine single nucleotide polymorphisms (SNPs) were genotyped in 3,885 non-diabetic and 1,038 diabetic individuals with available measures of height, weight and BMI. Adipose mass and distribution was objectively assessed using dual energy X-ray absorptiometry (DEXA) in a sub-group of non-diabetics (n=2,206). In models with adipose mass traits, BMI or obesity as outcomes, the most strongly associated SNP was FTO rs1121980 ( P <0.001). Five other SNPs ( SH2B1 rs7498665, MTCH2 rs4752856, MC4R rs17782313, NEGR1 rs2815752, and GNPDA2 rs10938397) were significantly associated with obesity. To summarize the overall genetic burden, a weighted risk score comprising a subset of SNPs was constructed; those in the top quintile of the score were heavier (+2.6kg) and had more total (+2.4kg), gynoid (+191g), and abdominal (+136g) adipose tissue than those in the lowest quintile (all P <0.001). The genetic burden score significantly increased diabetes risk, with those in the highest quintile (n=193/594 cases/controls) being at 1.55-fold (95% CI: 1.21-1.99; P <0.0001) greater risk of type 2 diabetes than those in the lowest quintile (n=130/655 cases/controls). In summary, we have statistically replicated six of the previously associated obese-risk loci and our results suggest that the weight-inducing effects of these variants are explained largely by increased adipose accumulation. |
format |
Text |
author |
Renström, Frida Payne, Felicity Nordström, Anna Brito, Ema C. GIANT Consortium, Rolandsson, Olov Hallmans, Göran Barroso, Ines Nordström, Peter Franks, Paul W. |
author_facet |
Renström, Frida Payne, Felicity Nordström, Anna Brito, Ema C. GIANT Consortium, Rolandsson, Olov Hallmans, Göran Barroso, Ines Nordström, Peter Franks, Paul W. |
author_sort |
Renström, Frida |
title |
Replication and extension of genome-wide association study results for obesity in 4,923 adults from Northern Sweden |
title_short |
Replication and extension of genome-wide association study results for obesity in 4,923 adults from Northern Sweden |
title_full |
Replication and extension of genome-wide association study results for obesity in 4,923 adults from Northern Sweden |
title_fullStr |
Replication and extension of genome-wide association study results for obesity in 4,923 adults from Northern Sweden |
title_full_unstemmed |
Replication and extension of genome-wide association study results for obesity in 4,923 adults from Northern Sweden |
title_sort |
replication and extension of genome-wide association study results for obesity in 4,923 adults from northern sweden |
publisher |
Oxford University Press |
publishDate |
2009 |
url |
http://hmg.oxfordjournals.org/cgi/content/short/ddp041v1 https://doi.org/10.1093/hmg/ddp041 |
genre |
Northern Sweden |
genre_facet |
Northern Sweden |
op_relation |
http://hmg.oxfordjournals.org/cgi/content/short/ddp041v1 http://dx.doi.org/10.1093/hmg/ddp041 |
op_rights |
Copyright (C) 2009, Oxford University Press |
op_doi |
https://doi.org/10.1093/hmg/ddp041 |
container_title |
Human Molecular Genetics |
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18 |
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8 |
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1489 |
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1496 |
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1766147203214082048 |