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Spracklen, C.N.* ; Karaderi, T.* ; Yaghootkar, H.* ; Schurmann, C.* ; Fine, R.S.* ; Kutalik, Z.* ; Preuss, M.H.* ; Lu, Y.* ; Wittemans, L.B.L.* ; Adair, L.S.* ; Allison, M.* ; Amin, N.* ; Auer, P.L.* ; Bartz, T.M.* ; Blüher, M.* ; Boehnke, M.* ; Borja, J.B.* ; Bork-Jensen, J.* ; Broer, L.* ; Chasman, D.I.* ; Chen, Y.I.* ; Chirstofidou, P.* ; Demirkan, A.* ; van Duijn, C.M.* ; Feitosa, M.F.* ; Garcia, M.E.* ; Graff, M.* ; Grallert, H. ; Grarup, N.* ; Guo, X.* ; Haesser, J.* ; Hansen, T.* ; Harris, T.B.* ; Highland, H.M.* ; Hong, J.* ; Ikram, M.A.* ; Ingelsson, E.* ; Jackson, R.* ; Jousilahti, P.* ; Kähönen, M.* ; Kizer, J.R.* ; Kovacs, P.* ; Kriebel, J. ; Laakso, M.* ; Lange, L.A.* ; Lehtimäki, T.* ; Li, J.* ; Li-Gao, R.* ; Lind, L.* ; Luan, J.* ; Lyytikäinen, L.P.* ; MacGregor, S.* ; Mackey, D.A.* ; Mahajan, A.* ; Mangino, M.* ; Männistö, S.* ; McCarthy, M.I.* ; McKnight, B.* ; Medina-Gomez, C.* ; Meigs, J.B.* ; Molnos, S. ; Mook-Kanamori, D.O.* ; Morris, A.P.* ; de Mutsert, R.* ; Nalls, M.A.* ; Nedeljkovic, I.* ; North, K.E.* ; Pennell, C.E.* ; Pradhan, A.D.* ; Province, M.A.* ; Raitakari, O.T.* ; Raulerson, C.K.* ; Reiner, A.P.* ; Ridker, P.M.* ; Ripatti, S.* ; Roberston, N.* ; Rotter, J.I.* ; Salomaa, V.* ; Sandoval-Zárate, A.A.* ; Sitlani, C.M.* ; Spector, T.D.* ; Strauch, K. ; Stumvoll, M.* ; Taylor, K.D.* ; Thuesen, B.* ; Tönjes, A.* ; Uitterlinden, A.G.* ; Venturini, C.* ; Walker, M.* ; Wang, C.A.* ; Wang, S.* ; Wareham, N.J.* ; Willems, S.M.* ; Willems van Dijk, K.* ; Wilson, J.G.* ; Wu, Y.* ; Yao, J.* ; Young, K.L.* ; Langenberg, C.* ; Frayling, T.M.* ; Kilpeläinen, T.O.* ; Lindgren, C.M.* ; Loos, R.J.F.* ; Mohlke, K.L.*

Exome-derived adiponectin-associated variants implicate obesity and lipid biology.

Am. J. Hum. Genet. 105, 15-28 (2019)
Publ. Version/Full Text Preprint DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Circulating levels of adiponectin, an adipocyte-secreted protein associated with cardiovascular and metabolic risk, are highly heritable. To gain insights into the biology that regulates adiponectin levels, we performed an exome array meta-analysis of 265,780 genetic variants in 67,739 individuals of European, Hispanic, African American, and East Asian ancestry. We identified 20 loci associated with adiponectin, including 11 that had been reported previously (p < 2 x 10(-7)). Comparison of exome array variants to regional linkage disequilibrium (LD) patterns and prior genome-wide association study (GWAS) results detected candidate variants (r(2) > .60) spanning as much as 900 kb. To identify potential genes and mechanisms through which the previously unreported association signals act to affect adiponectin levels, we assessed cross-trait associations, expression quantitative trait loci in subcutaneous adipose, and biological pathways of nearby genes. Eight of the nine loci were also associated (p < 1 x 10(-4)) with at least one obesity or lipid trait. Candidate genes include PRKAR2A, PTH1R, and HDAC9, which have been suggested to play roles in adipocyte differentiation or bone marrow adipose tissue. Taken together, these findings provide further insights into the processes that influence circulating adiponectin levels.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Adiponectin ; Cardio Metabolic Traits ; Exome ; Genetics ; Genome-wide Association Study ; Lipids ; Obesity; Genome-wide Association; Adipose-tissue; Plasma Adiponectin; Circulating Adiponectin; Glycemic Traits; Candidate Genes; Rare; Disease; Metaanalysis; Expression
Language english
Publication Year 2019
HGF-reported in Year 2019
ISSN (print) / ISBN 0002-9297
e-ISSN 1537-6605
Journal American Journal of Human Genetics, The
Quellenangaben Volume: 105, Issue: 1, Pages: 15-28 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place New York, NY
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)
Institute of Genetic Epidemiology (IGE)
POF-Topic(s) 30202 - Environmental Health
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
90000 - German Center for Diabetes Research
Research field(s) Genetics and Epidemiology
PSP Element(s) G-504091-002
G-504100-001
G-501900-402
DOI 10.1016/j.ajhg.2019.05.002
WOS ID WOS:000473723000003
PubMed ID 31178129
Erfassungsdatum 2019-06-13
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