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

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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 , Blueher , M , Boehnke , M , Borja , J B , Bork-Jensen , J , Broer , L , Chasman , D I , Chen , Y-D 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 , Kahonen , M , Kizer , J R , Kovacs , P , Kriebel , J , Laakso , M , Lange , L A , Lehtimaki , T , Li , J , Ruifang Li-Gao , Lind , L , Luan , J , Lyytikainen , 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-Zarate , A A , Sitlani , C M , Spector , T D , Strauch , K , Stumvoll , M , Taylor , K D , Thuesen , B , Toenjes , A , Uitterlinden , A G , Venturini , C , Walker , M , Wang , C A , Wang , S , Wareham , N J , Willems , S M , van Dijk , K W , Wilson , J G , Wu , Y , Yao , J , Young , K L , Langenberg , C , Frayling , T M , Kilpelainen , T O , Lindgren , C M , Loos , R J F & Mohlke , K L 2019 , ' Exome-Derived Adiponectin-Associated Variants Implicate Obesity and Lipid Biology ' , American Journal of Human Genetics , vol. 105 , no. 1 , pp. 15-28 . https://doi.org/10.1016/j.ajhg.2019.05.002

Title: Exome-Derived Adiponectin-Associated Variants Implicate Obesity and Lipid Biology
Author: Spracklen, Cassandra N.; Karaderi, Tugce; Yaghootkar, Hanieh; Schurmann, Claudia; Fine, Rebecca S.; Kutalik, Zoltan; Preuss, Michael H.; Lu, Yingchang; Wittemans, Laura B. L.; Adair, Linda S.; Allison, Matthew; Amin, Najaf; Auer, Paul L.; Bartz, Traci M.; Blueher, Matthias; Boehnke, Michael; Borja, Judith B.; Bork-Jensen, Jette; Broer, Linda; Chasman, Daniel I.; Chen, Yii-Der Ida; Chirstofidou, Paraskevi; Demirkan, Ayse; van Duijn, Cornelia M.; Feitosa, Mary F.; Garcia, Melissa E.; Graff, Mariaelisa; Grallert, Harald; Grarup, Niels; Guo, Xiuqing; Haesser, Jeffrey; Hansen, Torben; Harris, Tamara B.; Highland, Heather M.; Hong, Jaeyoung; Ikram, M. Arfan; Ingelsson, Erik; Jackson, Rebecca; Jousilahti, Pekka; Kahonen, Mika; Kizer, Jorge R.; Kovacs, Peter; Kriebel, Jennifer; Laakso, Markku; Lange, Leslie A.; Lehtimaki, Terho; Li, Jin; Ruifang Li-Gao,; Lind, Lars; Luan, Jian'an; Lyytikainen, Leo-Pekka; MacGregor, Stuart; Mackey, David A.; Mahajan, Anubha; Mangino, Massimo; Männistö, Satu; McCarthy, Mark I.; McKnight, Barbara; Medina-Gomez, Carolina; Meigs, James B.; Molnos, Sophie; Mook-Kanamori, Dennis; Morris, Andrew P.; de Mutsert, Renee; Nalls, Mike A.; Nedeljkovic, Ivana; North, Kari E.; Pennell, Craig E.; Pradhan, Aruna D.; Province, Michael A.; Raitakari, Olli T.; Raulerson, Chelsea K.; Reiner, Alex P.; Ridker, Paul M.; Ripatti, Samuli; Roberston, Neil; Rotter, Jerome I.; Salomaa, Veikko; Sandoval-Zarate, America A.; Sitlani, Colleen M.; Spector, Tim D.; Strauch, Konstantin; Stumvoll, Michael; Taylor, Kent D.; Thuesen, Betina; Toenjes, Anke; Uitterlinden, Andre G.; Venturini, Cristina; Walker, Mark; Wang, Carol A.; Wang, Shuai; Wareham, Nicholas J.; Willems, Sara M.; van Dijk, Ko Willems; Wilson, James G.; Wu, Ying; Yao, Jie; Young, Kristin L.; Langenberg, Claudia; Frayling, Timothy M.; Kilpelainen, Tuomas O.; Lindgren, Cecilia M.; Loos, Ruth J. F.; Mohlke, Karen L.
Contributor: University of Helsinki, Centre of Excellence in Complex Disease Genetics
University of Helsinki, Institute for Molecular Medicine Finland
Date: 2019-07-03
Language: eng
Number of pages: 14
Belongs to series: American Journal of Human Genetics
ISSN: 0002-9297
URI: http://hdl.handle.net/10138/312927
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 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.
Subject: GENOME-WIDE ASSOCIATION
ADIPOSE-TISSUE
PLASMA ADIPONECTIN
CIRCULATING ADIPONECTIN
GLYCEMIC TRAITS
CANDIDATE GENES
RARE
DISEASE
METAANALYSIS
EXPRESSION
3111 Biomedicine
1184 Genetics, developmental biology, physiology
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