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

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Harvard

Spracklen, CN, Karaderi, T, Yaghootkar, H, Schurmann, C, Fine, RS, Kutalik, Z, Preuss, MH, Lu, Y, Wittemans, LBL, Adair, LS, Allison, M, Amin, N, Auer, PL, Bartz, TM, Blüher, M, Boehnke, M, Borja, JB, Bork-Jensen, J, Broer, L, Chasman, DI, Chen, Y-DI, Chirstofidou, P, Demirkan, A, van Duijn, CM, Feitosa, MF, Garcia, ME, Graff, M, Grallert, H, Grarup, N, Guo, X, Haesser, J, Hansen, T, Harris, TB, Highland, HM, Hong, J, Ikram, MA, Ingelsson, E, Jackson, R, Jousilahti, P, Kähönen, M, Kizer, JR, Kovacs, P, Kriebel, J, Laakso, M, Lange, LA, Lehtimäki, T, Li, J, Li-Gao, R, Lind, L, Luan, J, Lyytikäinen, L-P, MacGregor, S, Mackey, DA, Mahajan, A, Mangino, M, Männistö, S, McCarthy, MI, McKnight, B, Medina-Gomez, C, Meigs, JB, Molnos, S, Mook-Kanamori, D, Morris, AP, de Mutsert, R, Nalls, MA, Nedeljkovic, I, North, KE, Pennell, CE, Pradhan, AD, Province, MA, Raitakari, OT, Raulerson, CK, Reiner, AP, Ridker, PM, Ripatti, S, Roberston, N, Rotter, JI, Salomaa, V, Sandoval-Zárate, AA, Sitlani, CM, Spector, TD, Strauch, K, Stumvoll, M, Taylor, KD, Thuesen, B, Tönjes, A, Uitterlinden, AG, Venturini, C, Walker, M, Wang, CA, Wang, S, Wareham, NJ, Willems, SM, Willems van Dijk, K, Wilson, JG, Wu, Y, Yao, J, Young, KL, Langenberg, C, Frayling, TM, Kilpeläinen, TO, Lindgren, CM, Loos, RJF & Mohlke, KL 2019, 'Exome-Derived Adiponectin-Associated Variants Implicate Obesity and Lipid Biology' American Journal of Human Genetics, bind 105, nr. 1, s. 15-28. https://doi.org/10.1016/j.ajhg.2019.05.002

APA

Spracklen, C. N., Karaderi, T., Yaghootkar, H., Schurmann, C., Fine, R. S., Kutalik, Z., ... Mohlke, K. L. (2019). Exome-Derived Adiponectin-Associated Variants Implicate Obesity and Lipid Biology. American Journal of Human Genetics, 105(1), 15-28. https://doi.org/10.1016/j.ajhg.2019.05.002

CBE

Spracklen CN, Karaderi T, Yaghootkar H, Schurmann C, Fine RS, Kutalik Z, Preuss MH, Lu Y, Wittemans LBL, Adair LS, Allison M, Amin N, Auer PL, Bartz TM, Blüher M, Boehnke M, Borja JB, Bork-Jensen J, Broer L, Chasman DI, Chen Y-DI, Chirstofidou P, Demirkan A, van Duijn CM, Feitosa MF, Garcia ME, Graff M, Grallert H, Grarup N, Guo X, Haesser J, Hansen T, Harris TB, Highland HM, Hong J, Ikram MA, Ingelsson E, Jackson R, Jousilahti P, Kähönen M, Kizer JR, Kovacs P, Kriebel J, Laakso M, Lange LA, Lehtimäki T, Li J, Li-Gao R, Lind L, Luan J, Lyytikäinen L-P, MacGregor S, Mackey DA, Mahajan A, Mangino M, Männistö S, McCarthy MI, McKnight B, Medina-Gomez C, Meigs JB, Molnos S, Mook-Kanamori D, Morris AP, de Mutsert R, Nalls MA, Nedeljkovic I, North KE, Pennell CE, Pradhan AD, Province MA, Raitakari OT, Raulerson CK, Reiner AP, Ridker PM, Ripatti S, Roberston N, Rotter JI, Salomaa V, Sandoval-Zárate AA, Sitlani CM, Spector TD, Strauch K, Stumvoll M, Taylor KD, Thuesen B, Tönjes A, Uitterlinden AG, Venturini C, Walker M, Wang CA, Wang S, Wareham NJ, Willems SM, Willems van Dijk K, Wilson JG, Wu Y, Yao J, Young KL, Langenberg C, Frayling TM, Kilpeläinen TO, Lindgren CM, Loos RJF, Mohlke KL. 2019. Exome-Derived Adiponectin-Associated Variants Implicate Obesity and Lipid Biology. American Journal of Human Genetics. 105(1):15-28. https://doi.org/10.1016/j.ajhg.2019.05.002

MLA

Vancouver

Spracklen CN, Karaderi T, Yaghootkar H, Schurmann C, Fine RS, Kutalik Z o.a. Exome-Derived Adiponectin-Associated Variants Implicate Obesity and Lipid Biology. American Journal of Human Genetics. 2019 jul 3;105(1):15-28. https://doi.org/10.1016/j.ajhg.2019.05.002

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 ; 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 ; Li-Gao, Ruifang ; Lind, Lars ; Luan, Jian'an ; Lyytikäinen, 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-Zárate, America A ; Sitlani, Colleen M ; Spector, Tim D ; Strauch, Konstantin ; Stumvoll, Michael ; Taylor, Kent D ; Thuesen, Betina ; Tönjes, Anke ; Uitterlinden, Andre G ; Venturini, Cristina ; Walker, Mark ; Wang, Carol A ; Wang, Shuai ; Wareham, Nicholas J ; Willems, Sara M ; Willems van Dijk, Ko ; Wilson, James G ; Wu, Ying ; Yao, Jie ; Young, Kristin L ; Langenberg, Claudia ; Frayling, Timothy M ; Kilpeläinen, Tuomas O ; Lindgren, Cecilia M ; Loos, Ruth J F ; Mohlke, Karen L. / Exome-Derived Adiponectin-Associated Variants Implicate Obesity and Lipid Biology. I: American Journal of Human Genetics. 2019 ; Bind 105, Nr. 1. s. 15-28.

Bibtex

@article{b1e21d2872684f9fb3db32a6055b9e5a,
title = "Exome-Derived Adiponectin-Associated Variants Implicate Obesity and Lipid Biology",
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.",
keywords = "adiponectin, cardio metabolic traits, exome, genetics, genome-wide association study, lipids, obesity",
author = "Spracklen, {Cassandra N} and Tugce Karaderi and Hanieh Yaghootkar and Claudia Schurmann and Fine, {Rebecca S} and Zoltan Kutalik and Preuss, {Michael H} and Yingchang Lu and Wittemans, {Laura B L} and Adair, {Linda S} and Matthew Allison and Najaf Amin and Auer, {Paul L} and Bartz, {Traci M} and Matthias Bl{\"u}her and Michael Boehnke and Borja, {Judith B} and Jette Bork-Jensen and Linda Broer and Chasman, {Daniel I} and Chen, {Yii-Der Ida} and Paraskevi Chirstofidou and Ayse Demirkan and {van Duijn}, {Cornelia M} and Feitosa, {Mary F} and Garcia, {Melissa E} and Mariaelisa Graff and Harald Grallert and Niels Grarup and Xiuqing Guo and Jeffrey Haesser and Torben Hansen and Harris, {Tamara B} and Highland, {Heather M} and Jaeyoung Hong and Ikram, {M Arfan} and Erik Ingelsson and Rebecca Jackson and Pekka Jousilahti and Mika K{\"a}h{\"o}nen and Kizer, {Jorge R} and Peter Kovacs and Jennifer Kriebel and Markku Laakso and Lange, {Leslie A} and Terho Lehtim{\"a}ki and Jin Li and Ruifang Li-Gao and Lars Lind and Jian'an Luan and Leo-Pekka Lyytik{\"a}inen and Stuart MacGregor and Mackey, {David A} and Anubha Mahajan and Massimo Mangino and Satu M{\"a}nnist{\"o} and McCarthy, {Mark I} and Barbara McKnight and Carolina Medina-Gomez and Meigs, {James B} and Sophie Molnos and Dennis Mook-Kanamori and Morris, {Andrew P} and {de Mutsert}, Renee and Nalls, {Mike A} and Ivana Nedeljkovic and North, {Kari E} and Pennell, {Craig E} and Pradhan, {Aruna D} and Province, {Michael A} and Raitakari, {Olli T} and Raulerson, {Chelsea K} and Reiner, {Alex P} and Ridker, {Paul M} and Samuli Ripatti and Neil Roberston and Rotter, {Jerome I} and Veikko Salomaa and Sandoval-Z{\'a}rate, {America A} and Sitlani, {Colleen M} and Spector, {Tim D} and Konstantin Strauch and Michael Stumvoll and Taylor, {Kent D} and Betina Thuesen and Anke T{\"o}njes and Uitterlinden, {Andre G} and Cristina Venturini and Mark Walker and Wang, {Carol A} and Shuai Wang and Wareham, {Nicholas J} and Willems, {Sara M} and {Willems van Dijk}, Ko and Wilson, {James G} and Ying Wu and Jie Yao and Young, {Kristin L} and Claudia Langenberg and Frayling, {Timothy M} and Kilpel{\"a}inen, {Tuomas O} and Lindgren, {Cecilia M} and Loos, {Ruth J F} and Mohlke, {Karen L}",
note = "Copyright {\circledC} 2019 American Society of Human Genetics. All rights reserved.",
year = "2019",
month = "7",
day = "3",
doi = "10.1016/j.ajhg.2019.05.002",
language = "English",
volume = "105",
pages = "15--28",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "1",

}

RIS

TY - JOUR

T1 - Exome-Derived Adiponectin-Associated Variants Implicate Obesity and Lipid Biology

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 - Li-Gao, Ruifang

AU - Lind, Lars

AU - Luan, Jian'an

AU - Lyytikäinen, Leo-Pekka

AU - MacGregor, Stuart

AU - Mackey, David A

AU - Mahajan, Anubha

AU - Mangino, Massimo

AU - Männistö, Satu

AU - McCarthy, Mark I

AU - McKnight, Barbara

AU - Medina-Gomez, Carolina

AU - Meigs, James B

AU - Molnos, Sophie

AU - Mook-Kanamori, Dennis

AU - Morris, Andrew P

AU - de Mutsert, Renee

AU - Nalls, Mike A

AU - Nedeljkovic, Ivana

AU - North, Kari E

AU - Pennell, Craig E

AU - Pradhan, Aruna D

AU - Province, Michael A

AU - Raitakari, Olli T

AU - Raulerson, Chelsea K

AU - Reiner, Alex P

AU - Ridker, Paul M

AU - Ripatti, Samuli

AU - Roberston, Neil

AU - Rotter, Jerome I

AU - Salomaa, Veikko

AU - Sandoval-Zárate, America A

AU - Sitlani, Colleen M

AU - Spector, Tim D

AU - Strauch, Konstantin

AU - Stumvoll, Michael

AU - Taylor, Kent D

AU - Thuesen, Betina

AU - Tönjes, Anke

AU - Uitterlinden, Andre G

AU - Venturini, Cristina

AU - Walker, Mark

AU - Wang, Carol A

AU - Wang, Shuai

AU - Wareham, Nicholas J

AU - Willems, Sara M

AU - Willems van Dijk, Ko

AU - Wilson, James G

AU - Wu, Ying

AU - Yao, Jie

AU - Young, Kristin L

AU - Langenberg, Claudia

AU - Frayling, Timothy M

AU - Kilpeläinen, Tuomas O

AU - Lindgren, Cecilia M

AU - Loos, Ruth J F

AU - Mohlke, Karen L

N1 - Copyright © 2019 American Society of Human Genetics. All rights reserved.

PY - 2019/7/3

Y1 - 2019/7/3

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 - http://www.scopus.com/inward/record.url?scp=85068057969&partnerID=8YFLogxK

U2 - 10.1016/j.ajhg.2019.05.002

DO - 10.1016/j.ajhg.2019.05.002

M3 - Journal article

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: 57912304