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dc.contributor.authorKilpeläinen, TO
dc.contributor.authorCarli, JF
dc.contributor.authorSkowronski, AA
dc.contributor.authorSun, Q
dc.contributor.authorKriebel, J
dc.contributor.authorFeitosa, MF
dc.contributor.authorHedman, ÅK
dc.contributor.authorDrong, AW
dc.contributor.authorHayes, JE
dc.contributor.authorZhao, J
dc.contributor.authorPers, TH
dc.contributor.authorSchick, U
dc.contributor.authorGrarup, N
dc.contributor.authorKutalik, Z
dc.contributor.authorTrompet, S
dc.contributor.authorMangino, M
dc.contributor.authorKristiansson, K
dc.contributor.authorBeekman, M
dc.contributor.authorLyytikäinen, LP
dc.contributor.authorEriksson, J et al
dc.date.accessioned2017-02-16T07:39:54Z
dc.date.available2017-02-16T07:39:54Z
dc.date.issued2016
dc.identifier10.1038/ncomms10494.fi_FI
dc.identifier.issn2041-1723
dc.identifier.urihttps://erepo.uef.fi/handle/123456789/287
dc.descriptionArticle
dc.description.abstractLeptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10−6 in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10−8) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.fi_FI
dc.language.isoENfi_FI
dc.publisherNature Publishing Groupfi_FI
dc.relation.ispartofseriesNature Communications
dc.relation.urihttp://doi.org/10.1038/ncomms10494fi_FI
dc.rightsCC BY http://creativecommons.org/licenses/by/4.0/fi_FI
dc.subjectClinical geneticsfi_FI
dc.subjectObesityfi_FI
dc.subjectPeptide hormonesfi_FI
dc.titleGenome-wide meta-analysis uncovers novel loci influencing circulating leptin levelsfi_FI
dc.typehttp://purl.org/eprint/type/JournalArticle
dc.description.versionPublisher's pdffi_FI
dc.contributor.departmentSchool of Medicine / Public Health
uef.solecris.id41738527
eprint.statushttp://purl.org/eprint/status/PeerReviewedfi_FI
dc.type.publicationinfo:eu-repo/semantics/article
dc.rights.accessrights© Authorsfi_FI
uef.citationinfo.issue7
uef.citationinfo.pages10494
dc.relation.doi10.1038/ncomms10494
dc.description.reviewstatushttp://purl.org/eprint/status/PeerReviewed
dc.relation.articlenumber10494
dc.relation.issn2041-1723
dc.relation.issue7


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