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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
dc.contributor.authorHenneman P
dc.contributor.authorLahti J
dc.contributor.authorTanaka T
dc.contributor.authorLuan J
dc.contributor.authorDel Greco M F
dc.contributor.authorPasko D
dc.contributor.authorRenström F
dc.contributor.authorWillems SM
dc.contributor.authorMahajan A
dc.contributor.authorRose LM
dc.contributor.authorGuo X
dc.contributor.authorLiu Y
dc.contributor.authorKleber ME
dc.contributor.authorPérusse L
dc.contributor.authorGaunt T
dc.contributor.authorAhluwalia TS
dc.contributor.authorJu Sung Y
dc.contributor.authorRamos YF
dc.contributor.authorAmin N
dc.contributor.authorAmuzu A
dc.contributor.authorBarroso I
dc.contributor.authorBellis C
dc.contributor.authorBlangero J
dc.contributor.authorBuckley BM
dc.contributor.authorBöhringer S
dc.contributor.authorI Chen YD
dc.contributor.authorde Craen AJ
dc.contributor.authorCrosslin DR
dc.contributor.authorDale CE
dc.contributor.authorDastani Z
dc.contributor.authorDay FR
dc.contributor.authorDeelen J
dc.contributor.authorDelgado GE
dc.contributor.authorDemirkan A
dc.contributor.authorFinucane FM
dc.contributor.authorFord I
dc.contributor.authorGarcia ME
dc.contributor.authorGieger C
dc.contributor.authorGustafsson S
dc.contributor.authorHallmans G
dc.contributor.authorHankinson SE
dc.contributor.authorHavulinna AS
dc.contributor.authorHerder C
dc.contributor.authorHernandez D
dc.contributor.authorHicks AA
dc.contributor.authorHunter DJ
dc.contributor.authorIllig T
dc.contributor.authorIngelsson E
dc.contributor.authorIoan-Facsinay A
dc.contributor.authorJansson JO
dc.contributor.authorJenny NS
dc.contributor.authorJørgensen ME
dc.contributor.authorJørgensen T
dc.contributor.authorKarlsson M
dc.contributor.authorKoenig W
dc.contributor.authorKraft P
dc.contributor.authorKwekkeboom J
dc.contributor.authorLaatikainen T
dc.contributor.authorLadwig KH
dc.contributor.authorLeDuc CA
dc.contributor.authorLowe G
dc.contributor.authorLu Y
dc.contributor.authorMarques-Vidal P
dc.contributor.authorMeisinger C
dc.contributor.authorMenni C
dc.contributor.authorMorris AP
dc.contributor.authorMyers RH
dc.contributor.authorMännistö S
dc.contributor.authorNalls MA
dc.contributor.authorPaternoster L
dc.contributor.authorPeters A
dc.contributor.authorPradhan AD
dc.contributor.authorRankinen T
dc.contributor.authorRasmussen-Torvik LJ
dc.contributor.authorRathmann W
dc.contributor.authorRice TK
dc.contributor.authorBrent Richards J
dc.contributor.authorRidker PM
dc.contributor.authorSattar N
dc.contributor.authorSavage DB
dc.contributor.authorSöderberg S
dc.contributor.authorTimpson NJ
dc.contributor.authorVandenput L
dc.contributor.authorvan Heemst D
dc.contributor.authorUh HW
dc.contributor.authorVohl MC
dc.contributor.authorWalker M
dc.contributor.authorWichmann HE
dc.contributor.authorWidén E
dc.contributor.authorWood AR
dc.contributor.authorYao J
dc.contributor.authorZeller T
dc.contributor.authorZhang Y
dc.contributor.authorMeulenbelt I
dc.contributor.authorKloppenburg M
dc.contributor.authorAstrup A
dc.contributor.authorSørensen TI
dc.contributor.authorSarzynski MA
dc.contributor.authorRao DC
dc.contributor.authorJousilahti P
dc.contributor.authorVartiainen E
dc.contributor.authorHofman A
dc.contributor.authorRivadeneira F
dc.contributor.authorUitterlinden AG
dc.contributor.authorKajantie E
dc.contributor.authorOsmond C
dc.contributor.authorPalotie A
dc.contributor.authorEriksson JG
dc.contributor.authorHeliövaara M
dc.contributor.authorKnekt PB
dc.contributor.authorKoskinen S
dc.contributor.authorJula A
dc.contributor.authorPerola M
dc.contributor.authorHuupponen RK
dc.contributor.authorViikari JS
dc.contributor.authorKähönen M
dc.contributor.authorLehtimäki T
dc.contributor.authorRaitakari OT
dc.contributor.authorMellström D
dc.contributor.authorLorentzon M
dc.contributor.authorCasas JP
dc.contributor.authorBandinelli S
dc.contributor.authorMärz W
dc.contributor.authorIsaacs A
dc.contributor.authorvan Dijk KW
dc.contributor.authorvan Duijn CM
dc.contributor.authorHarris TB
dc.contributor.authorBouchard C
dc.contributor.authorAllison MA
dc.contributor.authorChasman DI
dc.contributor.authorOhlsson C
dc.contributor.authorLind L
dc.contributor.authorScott RA
dc.contributor.authorLangenberg C
dc.contributor.authorWareham NJ
dc.contributor.authorFerrucci L
dc.contributor.authorFrayling TM
dc.contributor.authorPramstaller PP
dc.contributor.authorBorecki IB
dc.contributor.authorWaterworth DM
dc.contributor.authorBergmann S
dc.contributor.authorWaeber G
dc.contributor.authorVollenweider P
dc.contributor.authorVestergaard H
dc.contributor.authorHansen T
dc.contributor.authorPedersen O
dc.contributor.authorHu FB
dc.contributor.authorEline Slagboom P
dc.contributor.authorGrallert H
dc.contributor.authorSpector TD
dc.contributor.authorJukema JW
dc.contributor.authorKlein RJ
dc.contributor.authorSchadt EE
dc.contributor.authorFranks PW
dc.contributor.authorLindgren CM
dc.contributor.authorLeibel RL
dc.contributor.authorLoos RJ
dc.date.accessioned2018-10-08T14:19:18Z
dc.date.available2018-10-08T14:19:18Z
dc.date.issued2016
dc.identifier.issn2041-1723
dc.identifier.urihttp://dx.doi.org/10.1038/ncomms10494
dc.identifier.urihttp://hdl.handle.net/10863/6438
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.en_US
dc.language.isoenen_US
dc.rights
dc.titleGenome-wide meta-analysis uncovers novel loci influencing circulating leptin levelsen_US
dc.typeArticleen_US
dc.date.updated2018-10-08T14:17:47Z
dc.language.isiEN-GB
dc.journal.titleNature Communications
dc.description.fulltextopenen_US


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