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dc.contributor.authorDastani, Z
dc.contributor.authorHivert, M-F
dc.contributor.authorTimpson, N
dc.contributor.authorPerry, JRB
dc.contributor.authorYuan, X
dc.contributor.authorScott, RA
dc.contributor.authorHenneman, P
dc.contributor.authorHeid, IM
dc.contributor.authorKizer, JR
dc.contributor.authorLyytikainen, L-P
dc.contributor.authorFuchsberger, C
dc.contributor.authorTanaka, T
dc.contributor.authorMorris, AP
dc.contributor.authorSmall, K
dc.contributor.authorIsaacs, A
dc.contributor.authorBeekman, M
dc.contributor.authorCoassin, S
dc.contributor.authorLohman, K
dc.contributor.authorQi, L
dc.contributor.authorKanoni, S
dc.contributor.authorPankow, JS
dc.contributor.authorUh, H-W
dc.contributor.authorWu, Y
dc.contributor.authorBidulescu, A
dc.contributor.authorRasmussen-Torvik, LJ
dc.contributor.authorGreenwood, CMT
dc.contributor.authorLadouceur, M
dc.contributor.authorGrimsby, J
dc.contributor.authorManning, AK
dc.contributor.authorLiu, C-T
dc.contributor.authorKooner, J
dc.contributor.authorMooser, VE
dc.contributor.authorVollenweider, P
dc.contributor.authorKapur, KA
dc.contributor.authorChambers, J
dc.contributor.authorWareham, NJ
dc.contributor.authorLangenberg, C
dc.contributor.authorFrants, R
dc.contributor.authorWillems-vanDijk, K
dc.contributor.authorOostra, BA
dc.contributor.authorWillems, SM
dc.contributor.authorLamina, C
dc.contributor.authorWinkler, TW
dc.contributor.authorPsaty, BM
dc.contributor.authorTracy, RP
dc.contributor.authorBrody, J
dc.contributor.authorChen, I
dc.contributor.authorViikari, J
dc.contributor.authorKahonen, M
dc.contributor.authorPramstaller, PP
dc.contributor.authorEvans, DM
dc.contributor.authorSt Pourcain, B
dc.contributor.authorSattar, N
dc.contributor.authorWood, AR
dc.contributor.authorBandinelli, S
dc.contributor.authorCarlson, OD
dc.contributor.authorEgan, JM
dc.contributor.authorBohringer, S
dc.contributor.authorvan Heemst, D
dc.contributor.authorKedenko, L
dc.contributor.authorKristiansson, K
dc.contributor.authorNuotio, M-L
dc.contributor.authorLoo, B-M
dc.contributor.authorHarris, T
dc.contributor.authorGarcia, M
dc.contributor.authorKanaya, A
dc.contributor.authorHaun, M
dc.contributor.authorKlopp, N
dc.contributor.authorWichmann, H-E
dc.contributor.authorDeloukas, P
dc.contributor.authorKatsareli, E
dc.contributor.authorCouper, DJ
dc.contributor.authorDuncan, BB
dc.contributor.authorKloppenburg, M
dc.contributor.authorAdair, LS
dc.contributor.authorBorja, JB
dc.contributor.authorWilson, JG
dc.contributor.authorMusani, S
dc.contributor.authorGuo, X
dc.contributor.authorJohnson, T
dc.contributor.authorSemple, R
dc.contributor.authorTeslovich, TM
dc.contributor.authorAllison, MA
dc.contributor.authorRedline, S
dc.contributor.authorBuxbaum, SG
dc.contributor.authorMohlke, KL
dc.contributor.authorMeulenbelt, I
dc.contributor.authorBallantyne, CM
dc.contributor.authorDedoussis, GV
dc.contributor.authorHu, FB
dc.contributor.authorLiu, Y
dc.contributor.authorPaulweber, B
dc.contributor.authorSpector, TD
dc.contributor.authorSlagboom, PE
dc.contributor.authorFerrucci, L
dc.contributor.authorJula, A
dc.contributor.authorPerola, M
dc.contributor.authorRaitakari, O
dc.contributor.authorFlorez, JC
dc.contributor.authorSalomaa, V
dc.contributor.authorEriksson, JG
dc.contributor.authorFrayling, TM
dc.contributor.authorHicks, AA
dc.contributor.authorLehtimaki, T
dc.contributor.authorSmith, GD
dc.contributor.authorSiscovick, DS
dc.contributor.authorKronenberg, F
dc.contributor.authorvan Duijn, C
dc.contributor.authorLoos, RJF
dc.contributor.authorWaterworth, DM
dc.contributor.authorMeigs, JB
dc.contributor.authorDupuis, J
dc.contributor.authorRichards, JB
dc.date.accessioned2021-02-04T02:13:51Z
dc.date.available2021-02-04T02:13:51Z
dc.date.issued2012-03-01
dc.identifierpii: PGENETICS-D-11-02099
dc.identifier.citationDastani, Z., Hivert, M. -F., Timpson, N., Perry, J. R. B., Yuan, X., Scott, R. A., Henneman, P., Heid, I. M., Kizer, J. R., Lyytikainen, L. -P., Fuchsberger, C., Tanaka, T., Morris, A. P., Small, K., Isaacs, A., Beekman, M., Coassin, S., Lohman, K., Qi, L. ,... Richards, J. B. (2012). Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits: A Multi-Ethnic Meta-Analysis of 45,891 Individuals. PLOS GENETICS, 8 (3), https://doi.org/10.1371/journal.pgen.1002607.
dc.identifier.issn1553-7404
dc.identifier.urihttp://hdl.handle.net/11343/259617
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.languageEnglish
dc.publisherPUBLIC LIBRARY SCIENCE
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
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.typeJournal Article
dc.identifier.doi10.1371/journal.pgen.1002607
melbourne.affiliation.departmentClinical Pathology
melbourne.affiliation.departmentMicrobiology and Immunology
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titlePLoS Genetics
melbourne.source.volume8
melbourne.source.issue3
dc.rights.licenseCC BY
melbourne.elementsid1220632
melbourne.contributor.authorHofmann, Oliver
melbourne.contributor.authorCoin, Lachlan
dc.identifier.eissn1553-7404
melbourne.accessrightsOpen Access


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