Exome-Derived Adiponectin-Associated Variants Implicate Obesity and Lipid Biology.

Details

Serval ID
serval:BIB_3EFCEA80D251
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Exome-Derived Adiponectin-Associated Variants Implicate Obesity and Lipid Biology.
Journal
American journal of human genetics
Author(s)
Spracklen C.N., Karaderi T., Yaghootkar H., Schurmann C., Fine R.S., Kutalik Z., Preuss M.H., Lu Y., Wittemans LBL, 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., 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 RJF, Mohlke K.L.
ISSN
1537-6605 (Electronic)
ISSN-L
0002-9297
Publication state
Published
Issued date
03/07/2019
Peer-reviewed
Oui
Volume
105
Number
1
Pages
15-28
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
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 × 10 <sup>-7</sup> ). Comparison of exome array variants to regional linkage disequilibrium (LD) patterns and prior genome-wide association study (GWAS) results detected candidate variants (r <sup>2</sup> > .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 × 10 <sup>-4</sup> ) 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.
Keywords
adiponectin, cardio metabolic traits, exome, genetics, genome-wide association study, lipids, obesity
Pubmed
Web of science
Create date
24/06/2019 7:32
Last modification date
31/10/2019 16:37
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