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LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00004500naa a2200529 4500
001oai:DiVA.org:uu-157270
003SwePub
008110822s2011 | |||||||||||000 ||eng|
009oai:prod.swepub.kib.ki.se:123011810
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-1572702 URI
0247 a https://doi.org/10.1186/1755-8794-4-512 DOI
0247 a http://kipublications.ki.se/Default.aspx?queryparsed=id:1230118102 URI
040 a (SwePub)uud (SwePub)ki
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Jiao, Hongu Karolinska Institutet4 aut
2451 0a Genome wide association study identifies KCNMA1 contributing to human obesity
264 c 2011-06-28
264 1b Springer Science and Business Media LLC,c 2011
338 a print2 rdacarrier
520 a Background: 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. Methods: We performed a GWA analysis in 164 morbidly obese subjects (BMI: body mass index > 40 kg/m(2)) 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 P< 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 for 14 adults. Results: Potassium channel, calcium activated, large conductance, subfamily M, alpha member (KCNMA1) rs2116830*G and BDNF 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 KCNMA1 rs2116830*G with P = 2.82 x 10(-10) and an odds ratio (OR) based on cases vs controls of 1.26 [95% C. I. 1.12-1.41] and for BDNF rs988712*G with P = 5.2 x 10(-17) and an OR of 1.36 [95% C. I. 1.20-1.55]. KCNMA1 rs2116830*G was not associated with BMI in the population-based samples. Adipose tissue (P = 0.0001) and fat cell (P = 0.04) expression of KCNMA1 was increased in obesity. Conclusions: We have identified KCNMA1 as a new susceptibility locus for obesity, and confirmed the association of the BDNF locus at the genome-wide significant level.
653 a MEDICINE
653 a MEDICIN
7001 a Arner, Peteru Karolinska Institutet4 aut
7001 a Hoffstedt, Johan4 aut
7001 a Brodin, Davidu Karolinska Institutet4 aut
7001 a Dubern, Beatrice4 aut
7001 a Czernichow, Sebastien4 aut
7001 a van't Hooft, Ferdinandu Karolinska Institutet4 aut
7001 a Axelsson, Tomasu Uppsala universitet,Molekylär medicin,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)toaxe957
7001 a Pedersen, Oluf4 aut
7001 a Hansen, Torben4 aut
7001 a Sorensen, Thorkild I. A.4 aut
7001 a Hebebrand, Johannes4 aut
7001 a Kere, Juhau Karolinska Institutet4 aut
7001 a Dahlman-Wright, Karinu Karolinska Institutet4 aut
7001 a Hamsten, Andersu Karolinska Institutet4 aut
7001 a Clement, Karine4 aut
7001 a Dahlman, Ingridu Karolinska Institutet4 aut
7102 a Karolinska Institutetb Molekylär medicin4 org
7730 t BMC Medical Genomicsd : Springer Science and Business Media LLCg 4, s. 51-q 4<51-x 1755-8794
8564 u https://bmcmedgenomics.biomedcentral.com/track/pdf/10.1186/1755-8794-4-51
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-157270
8564 8u https://doi.org/10.1186/1755-8794-4-51
8564 8u http://kipublications.ki.se/Default.aspx?queryparsed=id:123011810

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