| Literature DB >> 31178129 |
Cassandra N Spracklen1, Tugce Karaderi2, Hanieh Yaghootkar3, Claudia Schurmann4, Rebecca S Fine5, Zoltan Kutalik6, Michael H Preuss4, Yingchang Lu7, Laura B L Wittemans8, Linda S Adair9, Matthew Allison10, Najaf Amin11, Paul L Auer12, Traci M Bartz13, Matthias Blüher14, Michael Boehnke15, Judith B Borja16, Jette Bork-Jensen17, Linda Broer18, Daniel I Chasman19, Yii-Der Ida Chen20, Paraskevi Chirstofidou21, Ayse Demirkan11, Cornelia M van Duijn11, Mary F Feitosa22, Melissa E Garcia23, Mariaelisa Graff24, Harald Grallert25, Niels Grarup17, Xiuqing Guo20, Jeffrey Haesser26, Torben Hansen17, Tamara B Harris27, Heather M Highland28, Jaeyoung Hong29, M Arfan Ikram30, Erik Ingelsson31, Rebecca Jackson32, Pekka Jousilahti33, Mika Kähönen34, Jorge R Kizer35, Peter Kovacs14, Jennifer Kriebel25, Markku Laakso36, Leslie A Lange37, Terho Lehtimäki38, Jin Li39, Ruifang Li-Gao40, Lars Lind41, Jian'an Luan42, Leo-Pekka Lyytikäinen43, Stuart MacGregor44, David A Mackey45, Anubha Mahajan46, Massimo Mangino47, Satu Männistö33, Mark I McCarthy48, Barbara McKnight49, Carolina Medina-Gomez30, James B Meigs50, Sophie Molnos25, Dennis Mook-Kanamori51, Andrew P Morris52, Renee de Mutsert40, Mike A Nalls53, Ivana Nedeljkovic11, Kari E North28, Craig E Pennell54, Aruna D Pradhan19, Michael A Province22, Olli T Raitakari55, Chelsea K Raulerson1, Alex P Reiner26, Paul M Ridker19, Samuli Ripatti56, Neil Roberston46, Jerome I Rotter20, Veikko Salomaa33, America A Sandoval-Zárate57, Colleen M Sitlani58, Tim D Spector21, Konstantin Strauch59, Michael Stumvoll14, Kent D Taylor20, Betina Thuesen60, Anke Tönjes14, Andre G Uitterlinden30, Cristina Venturini21, Mark Walker61, Carol A Wang54, Shuai Wang29, Nicholas J Wareham42, Sara M Willems42, Ko Willems van Dijk62, James G Wilson63, Ying Wu1, Jie Yao20, Kristin L Young28, Claudia Langenberg42, Timothy M Frayling64, Tuomas O Kilpeläinen65, Cecilia M Lindgren66, Ruth J F Loos67, Karen L Mohlke68.
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 × 10-7). Comparison of exome array variants to regional linkage disequilibrium (LD) patterns and prior genome-wide association study (GWAS) results detected candidate variants (r2 > .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 × 10-4) 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.Entities:
Keywords: adiponectin; cardio metabolic traits; exome; genetics; genome-wide association study; lipids; obesity
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Year: 2019 PMID： 31178129 PMCID： PMC6612516 DOI： 10.1016/j.ajhg.2019.05.002
Source DB: PubMed Journal: Am J Hum Genet ISSN： 0002-9297 Impact factor: 11.025