Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals

Zari Dastani; Marie-France Hivert; Nicholas Timpson; John R B Perry; Xin Yuan; Robert A Scott; Peter Henneman; Iris M Heid; Jorge R Kizer; Leo-Pekka Lyytikäinen; Christian Fuchsberger; Toshiko Tanaka; Andrew P Morris; Kerrin Small; Aaron Isaacs; Marian Beekman; Stefan Coassin; Kurt Lohman; Lu Qi; Stavroula Kanoni; James S Pankow; Hae-Won Uh; Ying Wu; Aurelian Bidulescu; Laura J Rasmussen-Torvik; Celia M T Greenwood; Martin Ladouceur; Jonna Grimsby; Alisa K Manning; Ching-Ti Liu; Jaspal Kooner; Vincent E Mooser; Peter Vollenweider; Karen A Kapur; John Chambers; Nicholas J Wareham; Claudia Langenberg; Rune Frants; Ko Willems-Vandijk; Ben A Oostra; Beate St Pourcain; George Davey Smith; Nicholas J Timpson; Yoav Ben-Shlomo; Ian N M Day; Mika Kivimaki; Debbie A Lawlor; Lyle J Palmer; Shah Ebrahim; Wendy McArdle; DIAGRAM+ Consortium

doi:10.1371/journal.pgen.1002607

Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals

Zari Dastani, Marie-France Hivert, Nicholas Timpson, John R B Perry, Xin Yuan, Robert A Scott, Peter Henneman, Iris M Heid, Jorge R Kizer, Leo-Pekka Lyytikäinen, Christian Fuchsberger, Toshiko Tanaka, Andrew P Morris, Kerrin Small, Aaron Isaacs, Marian Beekman, Stefan Coassin, Kurt Lohman, Lu Qi, Stavroula KanoniJames S Pankow, Hae-Won Uh, Ying Wu, Aurelian Bidulescu, Laura J Rasmussen-Torvik, Celia M T Greenwood, Martin Ladouceur, Jonna Grimsby, Alisa K Manning, Ching-Ti Liu, Jaspal Kooner, Vincent E Mooser, Peter Vollenweider, Karen A Kapur, John Chambers, Nicholas J Wareham, Claudia Langenberg, Rune Frants, Ko Willems-Vandijk, Ben A Oostra, Beate St Pourcain, George Davey Smith, Nicholas J Timpson, Yoav Ben-Shlomo, Ian N M Day, Mika Kivimaki, Debbie A Lawlor, Lyle J Palmer, Shah Ebrahim, Wendy McArdle, DIAGRAM+ Consortium

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Abstract

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p

Original language	English
Pages (from-to)	e1002607
Journal	PLoS Genetics
Volume	8
Issue number	3
DOIs	https://doi.org/10.1371/journal.pgen.1002607
Publication status	Published - 2012

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B603 THE EFFECT OF COMMON DISEASE ASSOCIATED GENETIC VARIANTS ON TRANSCRIPTOMIC AND EARLY LIFE PHENOTYPES
Evans, D. (Principal Investigator)
1/09/08 → 1/09/11
Project: Research
CENTRE FOR CASUAL ANALYSES IN TRANSLATIONAL EPIDEMIOLOGY (CAiTE)
Davey Smith, G. (Principal Investigator)
1/09/07 → 1/09/13
Project: Research

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Dastani, Z., Hivert, M.-F., Timpson, N., Perry, J. R. B., Yuan, X., Scott, R. A., Henneman, P., Heid, I. M., Kizer, J. R., Lyytikäinen, L.-P., Fuchsberger, C., Tanaka, T., Morris, A. P., Small, K., Isaacs, A., Beekman, M., Coassin, S., Lohman, K., Qi, L., ... DIAGRAM+ Consortium (2012). Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals. PLoS Genetics, 8(3), e1002607. https://doi.org/10.1371/journal.pgen.1002607

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abstract = "Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p",

author = "Zari Dastani and Marie-France Hivert and Nicholas Timpson and Perry, {John R B} and Xin Yuan and Scott, {Robert A} and Peter Henneman and Heid, {Iris M} and Kizer, {Jorge R} and Leo-Pekka Lyytik{\"a}inen and Christian Fuchsberger and Toshiko Tanaka and Morris, {Andrew P} and Kerrin Small and Aaron Isaacs and Marian Beekman and Stefan Coassin and Kurt Lohman and Lu Qi and Stavroula Kanoni and Pankow, {James S} and Hae-Won Uh and Ying Wu and Aurelian Bidulescu and Rasmussen-Torvik, {Laura J} and Greenwood, {Celia M T} and Martin Ladouceur and Jonna Grimsby and Manning, {Alisa K} and Ching-Ti Liu and Jaspal Kooner and Mooser, {Vincent E} and Peter Vollenweider and Kapur, {Karen A} and John Chambers and Wareham, {Nicholas J} and Claudia Langenberg and Rune Frants and Ko Willems-Vandijk and Oostra, {Ben A} and {St Pourcain}, Beate and Smith, {George Davey} and Timpson, {Nicholas J} and Yoav Ben-Shlomo and Day, {Ian N M} and Mika Kivimaki and Lawlor, {Debbie A} and Palmer, {Lyle J} and Shah Ebrahim and Wendy McArdle and {DIAGRAM+ Consortium}",

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Dastani, Z, Hivert, M-F, Timpson, N, Perry, JRB, Yuan, X, Scott, RA, Henneman, P, Heid, IM, Kizer, JR, Lyytikäinen, L-P, Fuchsberger, C, Tanaka, T, Morris, AP, Small, K, Isaacs, A, Beekman, M, Coassin, S, Lohman, K, Qi, L, Kanoni, S, Pankow, JS, Uh, H-W, Wu, Y, Bidulescu, A, Rasmussen-Torvik, LJ, Greenwood, CMT, Ladouceur, M, Grimsby, J, Manning, AK, Liu, C-T, Kooner, J, Mooser, VE, Vollenweider, P, Kapur, KA, Chambers, J, Wareham, NJ, Langenberg, C, Frants, R, Willems-Vandijk, K, Oostra, BA, St Pourcain, B , Smith, GD , Timpson, NJ , Ben-Shlomo, Y, Day, INM, Kivimaki, M, Lawlor, DA, Palmer, LJ, Ebrahim, S, McArdle, W & DIAGRAM+ Consortium 2012, 'Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals', PLoS Genetics, vol. 8, no. 3, pp. e1002607. https://doi.org/10.1371/journal.pgen.1002607

TY - JOUR

T1 - Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits

T2 - a multi-ethnic meta-analysis of 45,891 individuals

AU - Dastani, Zari

AU - Hivert, Marie-France

AU - Timpson, Nicholas

AU - Perry, John R B

AU - Yuan, Xin

AU - Scott, Robert A

AU - Henneman, Peter

AU - Heid, Iris M

AU - Kizer, Jorge R

AU - Lyytikäinen, Leo-Pekka

AU - Fuchsberger, Christian

AU - Tanaka, Toshiko

AU - Morris, Andrew P

AU - Small, Kerrin

AU - Isaacs, Aaron

AU - Beekman, Marian

AU - Coassin, Stefan

AU - Lohman, Kurt

AU - Qi, Lu

AU - Kanoni, Stavroula

AU - Pankow, James S

AU - Uh, Hae-Won

AU - Wu, Ying

AU - Bidulescu, Aurelian

AU - Rasmussen-Torvik, Laura J

AU - Greenwood, Celia M T

AU - Ladouceur, Martin

AU - Grimsby, Jonna

AU - Manning, Alisa K

AU - Liu, Ching-Ti

AU - Kooner, Jaspal

AU - Mooser, Vincent E

AU - Vollenweider, Peter

AU - Kapur, Karen A

AU - Chambers, John

AU - Wareham, Nicholas J

AU - Langenberg, Claudia

AU - Frants, Rune

AU - Willems-Vandijk, Ko

AU - Oostra, Ben A

AU - St Pourcain, Beate

AU - Smith, George Davey

AU - Timpson, Nicholas J

AU - Ben-Shlomo, Yoav

AU - Day, Ian N M

AU - Kivimaki, Mika

AU - Lawlor, Debbie A

AU - Palmer, Lyle J

AU - Ebrahim, Shah

AU - McArdle, Wendy

AU - DIAGRAM+ Consortium

PY - 2012

Y1 - 2012

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AB - Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p

U2 - 10.1371/journal.pgen.1002607

DO - 10.1371/journal.pgen.1002607

M3 - Article (Academic Journal)

C2 - 22479202

SN - 1553-7404

VL - 8

SP - e1002607

JO - PLoS Genetics

JF - PLoS Genetics

IS - 3

ER -

Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals

Abstract

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B603 THE EFFECT OF COMMON DISEASE ASSOCIATED GENETIC VARIANTS ON TRANSCRIPTOMIC AND EARLY LIFE PHENOTYPES

CENTRE FOR CASUAL ANALYSES IN TRANSLATIONAL EPIDEMIOLOGY (CAiTE)

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