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dc.contributor.authorDastani, Zari
dc.contributor.authorHivert, Marie-France
dc.contributor.authorTimpson, Nicholas
dc.contributor.authorPerry, John RB
dc.contributor.authorYuan, Xin
dc.contributor.authorScott, Robert A
dc.contributor.authorHenneman, Peter
dc.contributor.authorHeid, Iris M
dc.contributor.authorKizer, Jorge R
dc.contributor.authorLyytikäinen, Leo-Pekka
dc.contributor.authorFuchsberger, Christian
dc.contributor.authorTanaka, Toshiko
dc.contributor.authorMorris, Andrew P
dc.contributor.authorSmall, Kerrin
dc.contributor.authorIsaacs, Aaron
dc.contributor.authorBeekman, Marian
dc.contributor.authorCoassin, Stefan
dc.contributor.authorLohman, Kurt
dc.contributor.authorQi, Lu
dc.contributor.authorKanoni, Stavroula
dc.contributor.authorPankow, James S
dc.contributor.authorUh, Hae-Won
dc.contributor.authorWu, Ying
dc.contributor.authorBidulescu, Aurelian
dc.contributor.authorRasmussen-Torvik, Laura J
dc.contributor.authorGreenwood, Celia MT
dc.contributor.authorLadouceur, Martin
dc.contributor.authorGrimsby, Jonna
dc.contributor.authorManning, Alisa K
dc.contributor.authorLiu, Ching-Ti
dc.contributor.authorKooner, Jaspal
dc.contributor.authorMooser, Vincent E
dc.contributor.authorVollenweider, Peter
dc.contributor.authorKapur, Karen A
dc.contributor.authorChambers, John
dc.contributor.authorWareham, Nicholas J
dc.contributor.authorLangenberg, Claudia
dc.contributor.authorFrants, Rune
dc.contributor.authorWillems-Vandijk, Ko
dc.contributor.authorOostra, Ben A
dc.contributor.authorWillems, Sara M
dc.contributor.authorLamina, Claudia
dc.contributor.authorWinkler, Thomas W
dc.contributor.authorPsaty, Bruce M
dc.contributor.authorTracy, Russell P
dc.contributor.authorBrody, Jennifer
dc.contributor.authorChen, Ida
dc.contributor.authorViikari, Jorma
dc.contributor.authorKähönen, Mika
dc.contributor.authorPramstaller, Peter P
dc.contributor.authorEvans, David M
dc.contributor.authorSt Pourcain, Beate
dc.contributor.authorSattar, Naveed
dc.contributor.authorWood, Andrew R
dc.contributor.authorBandinelli, Stefania
dc.contributor.authorCarlson, Olga D
dc.contributor.authorEgan, Josephine M
dc.contributor.authorBöhringer, Stefan
dc.contributor.authorvan Heemst, Diana
dc.contributor.authorKedenko, Lyudmyla
dc.contributor.authorKristiansson, Kati
dc.contributor.authorNuotio, Marja-Liisa
dc.contributor.authorLoo, Britt-Marie
dc.contributor.authorHarris, Tamara
dc.contributor.authorGarcia, Melissa
dc.contributor.authorKanaya, Alka
dc.contributor.authorHaun, Margot
dc.contributor.authorKlopp, Norman
dc.contributor.authorWichmann, H-Erich
dc.contributor.authorDeloukas, Panos
dc.contributor.authorKatsareli, Efi
dc.contributor.authorCouper, David J
dc.contributor.authorDuncan, Bruce B
dc.contributor.authorKloppenburg, Margreet
dc.contributor.authorAdair, Linda S
dc.contributor.authorBorja, Judith B
dc.contributor.authorDIAGRAM+ Consortium
dc.contributor.authorMAGIC Consortium
dc.contributor.authorGLGC Investigators
dc.contributor.authorMuTHER Consortium
dc.contributor.authorWilson, James G
dc.contributor.authorMusani, Solomon
dc.contributor.authorGuo, Xiuqing
dc.contributor.authorJohnson, Toby
dc.contributor.authorSemple, Robert
dc.contributor.authorTeslovich, Tanya M
dc.contributor.authorAllison, Matthew A
dc.contributor.authorRedline, Susan
dc.contributor.authorBuxbaum, Sarah G
dc.contributor.authorMohlke, Karen L
dc.contributor.authorMeulenbelt, Ingrid
dc.contributor.authorBallantyne, Christie M
dc.contributor.authorDedoussis, George V
dc.contributor.authorHu, Frank B
dc.contributor.authorLiu, Yongmei
dc.contributor.authorPaulweber, Bernhard
dc.contributor.authorSpector, Timothy D
dc.contributor.authorSlagboom, P Eline
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dc.contributor.authorPerola, Markus
dc.contributor.authorRaitakari, Olli
dc.contributor.authorFlorez, Jose C
dc.contributor.authorSalomaa, Veikko
dc.contributor.authorEriksson, Johan G
dc.contributor.authorFrayling, Timothy M
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dc.contributor.authorLehtimäki, Terho
dc.contributor.authorSmith, George Davey
dc.contributor.authorSiscovick, David S
dc.contributor.authorKronenberg, Florian
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dc.contributor.authorLoos, Ruth JF
dc.contributor.authorWaterworth, Dawn M
dc.contributor.authorMeigs, James B
dc.contributor.authorDupuis, Josee
dc.contributor.authorRichards, J Brent
dc.contributor.authorVoight, Benjamin F
dc.contributor.authorScott, Laura J
dc.contributor.authorSteinthorsdottir, Valgerdur
dc.contributor.authorDina, Christian
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dc.contributor.authorAulchenko, Yurii S
dc.contributor.authorThorleifsson, Gudmar
dc.contributor.authorMcCulloch, Laura J
dc.contributor.authorFerreira, Teresa
dc.contributor.authorGrallert, Harald
dc.contributor.authorAmin, Najaf
dc.contributor.authorWu, Guanming
dc.contributor.authorWiller, Cristen J
dc.contributor.authorRaychaudhuri, Soumya
dc.contributor.authorMcCarroll, Steve A
dc.contributor.authorHofmann, Oliver M
dc.contributor.authorSegrè, Ayellet V
dc.contributor.authorvan Hoek, Mandy
dc.contributor.authorNavarro, Pau
dc.contributor.authorArdlie, Kristin
dc.contributor.authorBalkau, Beverley
dc.contributor.authorBenediktsson, Rafn
dc.contributor.authorBennett, Amanda J
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dc.contributor.authorBoerwinkle, Eric
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dc.contributor.authorBravenboer, Bert
dc.contributor.authorBumpstead, Suzannah
dc.contributor.authorBurtt, Noël P
dc.contributor.authorCharpentier, Guillaume
dc.contributor.authorChines, Peter S
dc.contributor.authorCornelis, Marilyn
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dc.contributor.authorElliott, Katherine S
dc.contributor.authorElliott, Amanda L
dc.contributor.authorErdos, Michael R
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dc.contributor.authorFranklin, Christopher S
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dc.contributor.authorGieger, Christian
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dc.contributor.authorGreen, Todd
dc.contributor.authorGriffin, Simon
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dc.contributor.authorGuiducci, Candace
dc.contributor.authorHadjadj, Samy
dc.contributor.authorHassanali, Neelam
dc.contributor.authorHerder, Christian
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dc.contributor.authorJørgensen, Torben
dc.contributor.authorKao, Wen HL
dc.contributor.authorKong, Augustine
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dc.contributor.authorLauritzen, Torsten
dc.contributor.authorLi, Man
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dc.contributor.authorMidthjell, Kristian
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dc.contributor.authorPlatou, Carl
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dc.contributor.authorRathmann, Wolfgang
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dc.contributor.authorShrader, Peter
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dc.contributor.authorSparsø, Thomas
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dc.contributor.authorStringham, Heather M
dc.contributor.authorSun, Qi
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dc.contributor.authorHitman, Graham A
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dc.contributor.authorHottenga, Jouke Jan
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dc.contributor.authorAn, Ping
dc.contributor.authorO'Connell, Jeffrey
dc.contributor.authorLuan, Jian'an
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dc.contributor.authorRoccasecca, Rosa Maria
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dc.contributor.authorBergmann, Sven
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dc.contributor.authorBöttcher, Yvonne
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dc.contributor.authorChen, Yii-Der Ida
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dc.contributor.authorHan, Xijing
dc.contributor.authorHartikainen, Anna-Liisa
dc.contributor.authorHayward, Caroline
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dc.contributor.authorHercberg, Serge
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dc.contributor.authorO'Donnell, Christopher J
dc.contributor.authorNieminen, Markku S
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dc.contributor.authorMontgomery, Grant W
dc.contributor.authorMcArdle, Wendy
dc.contributor.authorMasson, David
dc.contributor.authorMartin, Nicholas G
dc.contributor.authorMarroni, Fabio
dc.contributor.authorLucas, Gavin
dc.contributor.authorLuben, Robert
dc.contributor.authorLokki, Marja-Liisa
dc.contributor.authorLettre, Guillaume
dc.contributor.authorLauner, Lenore J
dc.contributor.authorLakatta, Edward G
dc.contributor.authorLaaksonen, Reijo
dc.contributor.authorKyvik, Kirsten O
dc.contributor.authorKönig, Inke R
dc.contributor.authorKhaw, Kay-Tee
dc.contributor.authorKaplan, Lee M
dc.contributor.authorJohansson, Åsa
dc.contributor.authorJanssens, A Cecile JW
dc.contributor.authorIgl, Wilmar
dc.contributor.authorHovingh, G Kees
dc.contributor.authorHengstenberg, Christian
dc.contributor.authorHavulinna, Aki S
dc.contributor.authorHastie, Nicholas D
dc.contributor.authorHarris, Tamara B
dc.contributor.authorHaritunians, Talin
dc.contributor.authorHall, Alistair S
dc.contributor.authorGroop, Leif C
dc.contributor.authorGonzalez, Elena
dc.contributor.authorFreimer, Nelson B
dc.contributor.authorErdmann, Jeanette
dc.contributor.authorEjebe, Kenechi G
dc.contributor.authorDöring, Angela
dc.contributor.authorDominiczak, Anna F
dc.contributor.authorDemissie, Serkalem
dc.contributor.authorDeloukas, Panagiotis
dc.contributor.authorde Faire, Ulf
dc.contributor.authorCrawford, Gabriel
dc.contributor.authorChen, Yii-der I
dc.contributor.authorCaulfield, Mark J
dc.contributor.authorBoekholdt, S Matthijs
dc.contributor.authorAssimes, Themistocles L
dc.contributor.authorQuertermous, Thomas
dc.contributor.authorSeielstad, Mark
dc.contributor.authorWong, Tien Y
dc.contributor.authorTai, E-Shyong
dc.contributor.authorFeranil, Alan B
dc.contributor.authorKuzawa, Christopher W
dc.contributor.authorTaylor, Herman A
dc.contributor.authorGabriel, Stacey B
dc.contributor.authorHolm, Hilma
dc.contributor.authorGudnason, Vilmundur
dc.contributor.authorKrauss, Ronald M
dc.contributor.authorOrdovas, Jose M
dc.contributor.authorMunroe, Patricia B
dc.contributor.authorKooner, Jaspal S
dc.contributor.authorTall, Alan R
dc.contributor.authorHegele, Robert A
dc.contributor.authorKastelein, John JP
dc.contributor.authorSchadt, Eric E
dc.contributor.authorStrachan, David P
dc.contributor.authorReilly, Muredach P
dc.contributor.authorSamani, Nilesh J
dc.contributor.authorSchunkert, Heribert
dc.contributor.authorCupples, L Adrienne
dc.contributor.authorSandhu, Manjinder S
dc.contributor.authorRidker, Paul M
dc.contributor.authorRader, Daniel J
dc.contributor.authorKathiresan, Sekar
dc.date.accessioned2018-01-23T16:59:22Z
dc.date.available2018-01-23T16:59:22Z
dc.date.issued2012
dc.identifier.issn1553-7390
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/271014
dc.description.abstractCirculating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10(-3), n = 22,044), increased triglycerides (p = 2.6×10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8×10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13), n = 96,748) and decreased BMI (p = 1.4×10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherPublic Library of Science (PLoS)
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectDIAGRAM+ Consortium
dc.subjectMAGIC Consortium
dc.subjectGLGC Investigators
dc.subjectMuTHER Consortium
dc.subjectDIAGRAM Consortium
dc.subjectGIANT Consortium
dc.subjectGlobal B Pgen Consortium
dc.subjectProcardis Consortium
dc.subjectMAGIC investigators
dc.subjectGLGC Consortium
dc.subjectHumans
dc.subjectDiabetes Mellitus, Type 2
dc.subjectInsulin Resistance
dc.subjectGenetic Predisposition to Disease
dc.subjectGlucose Tolerance Test
dc.subjectWaist-Hip Ratio
dc.subjectGene Expression
dc.subjectPolymorphism, Single Nucleotide
dc.subjectAfrican Americans
dc.subjectAsian Continental Ancestry Group
dc.subjectEuropean Continental Ancestry Group
dc.subjectFemale
dc.subjectMale
dc.subjectAdiponectin
dc.subjectCholesterol, HDL
dc.subjectMetabolic Networks and Pathways
dc.subjectGenome-Wide Association Study
dc.titleNovel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.
dc.typeArticle
prism.issueIdentifier3
prism.publicationDate2012
prism.publicationNamePLoS Genet
prism.startingPagee1002607
prism.volume8
dc.identifier.doi10.17863/CAM.17973
dcterms.dateAccepted2012-02-03
rioxxterms.versionofrecord10.1371/journal.pgen.1002607
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2012-01
dc.contributor.orcidPerry, John [0000-0001-6483-3771]
dc.contributor.orcidWareham, Nicholas [0000-0003-1422-2993]
dc.contributor.orcidLangenberg, Claudia [0000-0002-5017-7344]
dc.contributor.orcidSemple, Robert [0000-0001-6539-3069]
dc.contributor.orcidGriffin, Simon [0000-0002-2157-4797]
dc.contributor.orcidBarroso, Ines [0000-0001-5800-4520]
dc.contributor.orcidSoranzo, Nicole [0000-0003-1095-3852]
dc.contributor.orcidWheeler, Eleanor [0000-0002-8616-6444]
dc.contributor.orcidLuan, Jian'an [0000-0003-3137-6337]
dc.contributor.orcidForouhi, Nita [0000-0002-5041-248X]
dc.contributor.orcidSharp, Stephen [0000-0003-2375-1440]
dc.contributor.orcidSovio, Ulla [0000-0002-0799-1105]
dc.contributor.orcidZhao, Jing Hua [0000-0003-4930-3582]
dc.contributor.orcidLuben, Robert [0000-0002-5088-6343]
dc.contributor.orcidKhaw, Kay-Tee [0000-0002-8802-2903]
dc.contributor.orcidSandhu, Manjinder [0000-0002-2725-142X]
dc.identifier.eissn1553-7404
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMedical Research Council (G0401527)
pubs.funder-project-idMedical Research Council (G0901213)
pubs.funder-project-idMedical Research Council (G1000143)
pubs.funder-project-idMedical Research Council (MR/K013491/1)
pubs.funder-project-idBritish Heart Foundation (None)
pubs.funder-project-idMedical Research Council (G0701863)
pubs.funder-project-idMedical Research Council (MC_UU_12015/1)
pubs.funder-project-idMedical Research Council (G0600717)
pubs.funder-project-idMedical Research Council (MC_U106179471)
pubs.funder-project-idWellcome Trust (092447/Z/10/Z)
cam.issuedOnline2012-03-29


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International