Genome wide association study identifies <it>KCNMA1 </it>contributing to human obesity
<p>Abstract</p> <p>Background</p> <p>Recent genome-wide association (GWA) analyses have identified common single nucleotide polymorphisms (SNPs) that are associated with obesity. However, the reported genetic variation in obesity explains only a minor fraction of the to...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2011-06-01
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| Series: | BMC Medical Genomics |
| Online Access: | http://www.biomedcentral.com/1755-8794/4/51 |
| _version_ | 1818901430891708416 |
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| author | Sørensen Thorkild IA Hebebrand Johannes Hansen Torben Pedersen Oluf Axelsson Tomas van't Hooft Ferdinand Czernichow Sébastien Dubern Beatrice Brodin David Hoffstedt Johan Arner Peter Jiao Hong Kere Juha Dahlman-Wright Karin Hamsten Anders Clement Karine Dahlman Ingrid |
| author_facet | Sørensen Thorkild IA Hebebrand Johannes Hansen Torben Pedersen Oluf Axelsson Tomas van't Hooft Ferdinand Czernichow Sébastien Dubern Beatrice Brodin David Hoffstedt Johan Arner Peter Jiao Hong Kere Juha Dahlman-Wright Karin Hamsten Anders Clement Karine Dahlman Ingrid |
| author_sort | Sørensen Thorkild IA |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Recent genome-wide association (GWA) analyses have identified common single nucleotide polymorphisms (SNPs) that are associated with obesity. However, the reported genetic variation in obesity explains only a minor fraction of the total genetic variation expected to be present in the population. Thus many genetic variants controlling obesity remain to be identified. The aim of this study was to use GWA followed by multiple stepwise validations to identify additional genes associated with obesity.</p> <p>Methods</p> <p>We performed a GWA analysis in 164 morbidly obese subjects (BMI:body mass index > 40 kg/m<sup>2</sup>) and 163 Swedish subjects (> 45 years) who had always been lean. The 700 SNPs displaying the strongest association with obesity in the GWA were analyzed in a second cohort comprising 460 morbidly obese subjects and 247 consistently lean Swedish adults. 23 SNPs remained significantly associated with obesity (nominal <it>P</it>< 0.05) and were in a step-wise manner followed up in five additional cohorts from Sweden, France, and Germany together comprising 4214 obese and 5417 lean or population-based control individuals. Three samples, n = 4133, were used to investigate the population-based associations with BMI. Gene expression in abdominal subcutaneous adipose tissue in relation to obesity was investigated for14 adults.</p> <p>Results</p> <p>Potassium channel, calcium activated, large conductance, subfamily M, alpha member <it>(KCNMA1) </it>rs2116830*G and <it>BDNF </it>rs988712*G were associated with obesity in five of six investigated case-control cohorts. In meta-analysis of 4838 obese and 5827 control subjects we obtained genome-wide significant allelic association with obesity for <it>KCNMA1 </it>rs2116830*G with <it>P </it>= 2.82 × 10<sup>-10 </sup>and an odds ratio (OR) based on cases vs controls of 1.26 [95% C.I. 1.12-1.41] and for <it>BDNF </it>rs988712*G with <it>P </it>= 5.2 × 10<sup>-17</sup>and an OR of 1.36 [95% C.I. 1.20-1.55]. <it>KCNMA1 </it>rs2116830*G was not associated with BMI in the population-based samples. Adipose tissue (<it>P </it>= 0.0001) and fat cell (<it>P </it>= 0.04) expression of <it>KCNMA1 </it>was increased in obesity.</p> <p>Conclusions</p> <p>We have identified <it>KCNMA1 </it>as a new susceptibility locus for obesity, and confirmed the association of the <it>BDNF </it>locus at the genome-wide significant level.</p> |
| first_indexed | 2024-12-19T20:19:38Z |
| format | Article |
| id | doaj.art-d5157f412ef44bcba78011c9e21f1a0b |
| institution | Directory Open Access Journal |
| issn | 1755-8794 |
| language | English |
| last_indexed | 2024-12-19T20:19:38Z |
| publishDate | 2011-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genomics |
| spelling | doaj.art-d5157f412ef44bcba78011c9e21f1a0b2022-12-21T20:07:02ZengBMCBMC Medical Genomics1755-87942011-06-01415110.1186/1755-8794-4-51Genome wide association study identifies <it>KCNMA1 </it>contributing to human obesitySørensen Thorkild IAHebebrand JohannesHansen TorbenPedersen OlufAxelsson Tomasvan't Hooft FerdinandCzernichow SébastienDubern BeatriceBrodin DavidHoffstedt JohanArner PeterJiao HongKere JuhaDahlman-Wright KarinHamsten AndersClement KarineDahlman Ingrid<p>Abstract</p> <p>Background</p> <p>Recent genome-wide association (GWA) analyses have identified common single nucleotide polymorphisms (SNPs) that are associated with obesity. However, the reported genetic variation in obesity explains only a minor fraction of the total genetic variation expected to be present in the population. Thus many genetic variants controlling obesity remain to be identified. The aim of this study was to use GWA followed by multiple stepwise validations to identify additional genes associated with obesity.</p> <p>Methods</p> <p>We performed a GWA analysis in 164 morbidly obese subjects (BMI:body mass index > 40 kg/m<sup>2</sup>) and 163 Swedish subjects (> 45 years) who had always been lean. The 700 SNPs displaying the strongest association with obesity in the GWA were analyzed in a second cohort comprising 460 morbidly obese subjects and 247 consistently lean Swedish adults. 23 SNPs remained significantly associated with obesity (nominal <it>P</it>< 0.05) and were in a step-wise manner followed up in five additional cohorts from Sweden, France, and Germany together comprising 4214 obese and 5417 lean or population-based control individuals. Three samples, n = 4133, were used to investigate the population-based associations with BMI. Gene expression in abdominal subcutaneous adipose tissue in relation to obesity was investigated for14 adults.</p> <p>Results</p> <p>Potassium channel, calcium activated, large conductance, subfamily M, alpha member <it>(KCNMA1) </it>rs2116830*G and <it>BDNF </it>rs988712*G were associated with obesity in five of six investigated case-control cohorts. In meta-analysis of 4838 obese and 5827 control subjects we obtained genome-wide significant allelic association with obesity for <it>KCNMA1 </it>rs2116830*G with <it>P </it>= 2.82 × 10<sup>-10 </sup>and an odds ratio (OR) based on cases vs controls of 1.26 [95% C.I. 1.12-1.41] and for <it>BDNF </it>rs988712*G with <it>P </it>= 5.2 × 10<sup>-17</sup>and an OR of 1.36 [95% C.I. 1.20-1.55]. <it>KCNMA1 </it>rs2116830*G was not associated with BMI in the population-based samples. Adipose tissue (<it>P </it>= 0.0001) and fat cell (<it>P </it>= 0.04) expression of <it>KCNMA1 </it>was increased in obesity.</p> <p>Conclusions</p> <p>We have identified <it>KCNMA1 </it>as a new susceptibility locus for obesity, and confirmed the association of the <it>BDNF </it>locus at the genome-wide significant level.</p>http://www.biomedcentral.com/1755-8794/4/51 |
| spellingShingle | Sørensen Thorkild IA Hebebrand Johannes Hansen Torben Pedersen Oluf Axelsson Tomas van't Hooft Ferdinand Czernichow Sébastien Dubern Beatrice Brodin David Hoffstedt Johan Arner Peter Jiao Hong Kere Juha Dahlman-Wright Karin Hamsten Anders Clement Karine Dahlman Ingrid Genome wide association study identifies <it>KCNMA1 </it>contributing to human obesity BMC Medical Genomics |
| title | Genome wide association study identifies <it>KCNMA1 </it>contributing to human obesity |
| title_full | Genome wide association study identifies <it>KCNMA1 </it>contributing to human obesity |
| title_fullStr | Genome wide association study identifies <it>KCNMA1 </it>contributing to human obesity |
| title_full_unstemmed | Genome wide association study identifies <it>KCNMA1 </it>contributing to human obesity |
| title_short | Genome wide association study identifies <it>KCNMA1 </it>contributing to human obesity |
| title_sort | genome wide association study identifies it kcnma1 it contributing to human obesity |
| url | http://www.biomedcentral.com/1755-8794/4/51 |
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