Exome-Derived Adiponectin-Associated Variants Implicate Obesity and Lipid Biology: [incl. correction]
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Exome-Derived Adiponectin-Associated Variants Implicate Obesity and Lipid Biology : [incl. correction]. / 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.; Blüher, 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; Kähönen, Mika; Kizer, Jorge R.; Kovacs, Peter; Kriebel, Jennifer; Laakso, Markku; Lange, Leslie A.; Lehtimäki, Terho; Li, Jin; Lind, Lars; Kilpeläinen, Tuomas O.; Loos, Ruth J.F.; Mohlke, Karen L.
I: American Journal of Human Genetics, Bind 105, Nr. 1, 2019, s. 15-28.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Exome-Derived Adiponectin-Associated Variants Implicate Obesity and Lipid Biology
T2 - [incl. correction]
AU - Spracklen, Cassandra N.
AU - Karaderi, Tugce
AU - Yaghootkar, Hanieh
AU - Schurmann, Claudia
AU - Fine, Rebecca S.
AU - Kutalik, Zoltan
AU - Preuss, Michael H.
AU - Lu, Yingchang
AU - Wittemans, Laura B.L.
AU - Adair, Linda S.
AU - Allison, Matthew
AU - Amin, Najaf
AU - Auer, Paul L.
AU - Bartz, Traci M.
AU - Blüher, Matthias
AU - Boehnke, Michael
AU - Borja, Judith B.
AU - Bork-Jensen, Jette
AU - Broer, Linda
AU - Chasman, Daniel I.
AU - Chen, Yii Der Ida
AU - Chirstofidou, Paraskevi
AU - Demirkan, Ayse
AU - van Duijn, Cornelia M.
AU - Feitosa, Mary F.
AU - Garcia, Melissa E.
AU - Graff, Mariaelisa
AU - Grallert, Harald
AU - Grarup, Niels
AU - Guo, Xiuqing
AU - Haesser, Jeffrey
AU - Hansen, Torben
AU - Harris, Tamara B.
AU - Highland, Heather M.
AU - Hong, Jaeyoung
AU - Ikram, M. Arfan
AU - Ingelsson, Erik
AU - Jackson, Rebecca
AU - Jousilahti, Pekka
AU - Kähönen, Mika
AU - Kizer, Jorge R.
AU - Kovacs, Peter
AU - Kriebel, Jennifer
AU - Laakso, Markku
AU - Lange, Leslie A.
AU - Lehtimäki, Terho
AU - Li, Jin
AU - Lind, Lars
AU - Kilpeläinen, Tuomas O.
AU - Loos, Ruth J.F.
AU - Mohlke, Karen L
N1 - Corretion to: Exome-Derived Adiponectin-Associated Variants Implicate Obesity and Lipid Biology DOI: 10.1016/j.ajhg.2019.08.001
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
KW - adiponectin
KW - cardio metabolic traits
KW - exome
KW - genetics
KW - genome-wide association study
KW - lipids
KW - obesity
UR - https://doi.org/10.1016/j.ajhg.2019.08.001
U2 - 10.1016/j.ajhg.2019.05.002
DO - 10.1016/j.ajhg.2019.05.002
M3 - Journal article
C2 - 31178129
AN - SCOPUS:85068057969
VL - 105
SP - 15
EP - 28
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 1
ER -
ID: 226394821