A genome-wide association study reveals variants in ARL15 that influence adiponectin levels.

The adipocyte-derived protein adiponectin is highly heritable and inversely associated with risk of type 2 diabetes mellitus (T2D) and coronary heart disease (CHD). We meta-analyzed 3 genome-wide association studies for circulating adiponectin levels (n = 8,531) and sought validation of the lead sin...

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Main Authors: J Brent Richards, Dawn Waterworth, Stephen O'Rahilly, Marie-France Hivert, Ruth J F Loos, John R B Perry, Toshiko Tanaka, Nicholas John Timpson, Robert K Semple, Nicole Soranzo, Kijoung Song, Nuno Rocha, Elin Grundberg, Josée Dupuis, Jose C Florez, Claudia Langenberg, Inga Prokopenko, Richa Saxena, Robert Sladek, Yurii Aulchenko, David Evans, Gerard Waeber, Jeanette Erdmann, Mary-Susan Burnett, Naveed Sattar, Joseph Devaney, Christina Willenborg, Aroon Hingorani, Jaquelin C M Witteman, Peter Vollenweider, Beate Glaser, Christian Hengstenberg, Luigi Ferrucci, David Melzer, Klaus Stark, John Deanfield, Janina Winogradow, Martina Grassl, Alistair S Hall, Josephine M Egan, John R Thompson, Sally L Ricketts, Inke R König, Wibke Reinhard, Scott Grundy, H-Erich Wichmann, Phil Barter, Robert Mahley, Y Antero Kesaniemi, Daniel J Rader, Muredach P Reilly, Stephen E Epstein, Alexandre F R Stewart, Cornelia M Van Duijn, Heribert Schunkert, Keith Burling, Panos Deloukas, Tomi Pastinen, Nilesh J Samani, Ruth McPherson, George Davey Smith, Timothy M Frayling, Nicholas J Wareham, James B Meigs, Vincent Mooser, Tim D Spector, GIANT Consortium
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2009-12-01
Series:PLoS Genetics
Online Access:http://europepmc.org/articles/PMC2781107?pdf=render
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spelling doaj-5ebadbaada2a4a9caf70475a98073cf42020-11-25T02:12:15ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042009-12-01512e100076810.1371/journal.pgen.1000768A genome-wide association study reveals variants in ARL15 that influence adiponectin levels.J Brent RichardsDawn WaterworthStephen O'RahillyMarie-France HivertRuth J F LoosJohn R B PerryToshiko TanakaNicholas John TimpsonRobert K SempleNicole SoranzoKijoung SongNuno RochaElin GrundbergJosée DupuisJose C FlorezClaudia LangenbergInga ProkopenkoRicha SaxenaRobert SladekYurii AulchenkoDavid EvansGerard WaeberJeanette ErdmannMary-Susan BurnettNaveed SattarJoseph DevaneyChristina WillenborgAroon HingoraniJaquelin C M WittemanPeter VollenweiderBeate GlaserChristian HengstenbergLuigi FerrucciDavid MelzerKlaus StarkJohn DeanfieldJanina WinogradowMartina GrasslAlistair S HallJosephine M EganJohn R ThompsonSally L RickettsInke R KönigWibke ReinhardScott GrundyH-Erich WichmannPhil BarterRobert MahleyY Antero KesaniemiDaniel J RaderMuredach P ReillyStephen E EpsteinAlexandre F R StewartCornelia M Van DuijnHeribert SchunkertKeith BurlingPanos DeloukasTomi PastinenNilesh J SamaniRuth McPhersonGeorge Davey SmithTimothy M FraylingNicholas J WarehamJames B MeigsVincent MooserTim D SpectorGIANT ConsortiumThe adipocyte-derived protein adiponectin is highly heritable and inversely associated with risk of type 2 diabetes mellitus (T2D) and coronary heart disease (CHD). We meta-analyzed 3 genome-wide association studies for circulating adiponectin levels (n = 8,531) and sought validation of the lead single nucleotide polymorphisms (SNPs) in 5 additional cohorts (n = 6,202). Five SNPs were genome-wide significant in their relationship with adiponectin (P< or =5x10(-8)). We then tested whether these 5 SNPs were associated with risk of T2D and CHD using a Bonferroni-corrected threshold of P< or =0.011 to declare statistical significance for these disease associations. SNPs at the adiponectin-encoding ADIPOQ locus demonstrated the strongest associations with adiponectin levels (P-combined = 9.2x10(-19) for lead SNP, rs266717, n = 14,733). A novel variant in the ARL15 (ADP-ribosylation factor-like 15) gene was associated with lower circulating levels of adiponectin (rs4311394-G, P-combined = 2.9x10(-8), n = 14,733). This same risk allele at ARL15 was also associated with a higher risk of CHD (odds ratio [OR] = 1.12, P = 8.5x10(-6), n = 22,421) more nominally, an increased risk of T2D (OR = 1.11, P = 3.2x10(-3), n = 10,128), and several metabolic traits. Expression studies in humans indicated that ARL15 is well-expressed in skeletal muscle. These findings identify a novel protein, ARL15, which influences circulating adiponectin levels and may impact upon CHD risk.http://europepmc.org/articles/PMC2781107?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author J Brent Richards
Dawn Waterworth
Stephen O'Rahilly
Marie-France Hivert
Ruth J F Loos
John R B Perry
Toshiko Tanaka
Nicholas John Timpson
Robert K Semple
Nicole Soranzo
Kijoung Song
Nuno Rocha
Elin Grundberg
Josée Dupuis
Jose C Florez
Claudia Langenberg
Inga Prokopenko
Richa Saxena
Robert Sladek
Yurii Aulchenko
David Evans
Gerard Waeber
Jeanette Erdmann
Mary-Susan Burnett
Naveed Sattar
Joseph Devaney
Christina Willenborg
Aroon Hingorani
Jaquelin C M Witteman
Peter Vollenweider
Beate Glaser
Christian Hengstenberg
Luigi Ferrucci
David Melzer
Klaus Stark
John Deanfield
Janina Winogradow
Martina Grassl
Alistair S Hall
Josephine M Egan
John R Thompson
Sally L Ricketts
Inke R König
Wibke Reinhard
Scott Grundy
H-Erich Wichmann
Phil Barter
Robert Mahley
Y Antero Kesaniemi
Daniel J Rader
Muredach P Reilly
Stephen E Epstein
Alexandre F R Stewart
Cornelia M Van Duijn
Heribert Schunkert
Keith Burling
Panos Deloukas
Tomi Pastinen
Nilesh J Samani
Ruth McPherson
George Davey Smith
Timothy M Frayling
Nicholas J Wareham
James B Meigs
Vincent Mooser
Tim D Spector
GIANT Consortium
spellingShingle J Brent Richards
Dawn Waterworth
Stephen O'Rahilly
Marie-France Hivert
Ruth J F Loos
John R B Perry
Toshiko Tanaka
Nicholas John Timpson
Robert K Semple
Nicole Soranzo
Kijoung Song
Nuno Rocha
Elin Grundberg
Josée Dupuis
Jose C Florez
Claudia Langenberg
Inga Prokopenko
Richa Saxena
Robert Sladek
Yurii Aulchenko
David Evans
Gerard Waeber
Jeanette Erdmann
Mary-Susan Burnett
Naveed Sattar
Joseph Devaney
Christina Willenborg
Aroon Hingorani
Jaquelin C M Witteman
Peter Vollenweider
Beate Glaser
Christian Hengstenberg
Luigi Ferrucci
David Melzer
Klaus Stark
John Deanfield
Janina Winogradow
Martina Grassl
Alistair S Hall
Josephine M Egan
John R Thompson
Sally L Ricketts
Inke R König
Wibke Reinhard
Scott Grundy
H-Erich Wichmann
Phil Barter
Robert Mahley
Y Antero Kesaniemi
Daniel J Rader
Muredach P Reilly
Stephen E Epstein
Alexandre F R Stewart
Cornelia M Van Duijn
Heribert Schunkert
Keith Burling
Panos Deloukas
Tomi Pastinen
Nilesh J Samani
Ruth McPherson
George Davey Smith
Timothy M Frayling
Nicholas J Wareham
James B Meigs
Vincent Mooser
Tim D Spector
GIANT Consortium
A genome-wide association study reveals variants in ARL15 that influence adiponectin levels.
PLoS Genetics
author_facet J Brent Richards
Dawn Waterworth
Stephen O'Rahilly
Marie-France Hivert
Ruth J F Loos
John R B Perry
Toshiko Tanaka
Nicholas John Timpson
Robert K Semple
Nicole Soranzo
Kijoung Song
Nuno Rocha
Elin Grundberg
Josée Dupuis
Jose C Florez
Claudia Langenberg
Inga Prokopenko
Richa Saxena
Robert Sladek
Yurii Aulchenko
David Evans
Gerard Waeber
Jeanette Erdmann
Mary-Susan Burnett
Naveed Sattar
Joseph Devaney
Christina Willenborg
Aroon Hingorani
Jaquelin C M Witteman
Peter Vollenweider
Beate Glaser
Christian Hengstenberg
Luigi Ferrucci
David Melzer
Klaus Stark
John Deanfield
Janina Winogradow
Martina Grassl
Alistair S Hall
Josephine M Egan
John R Thompson
Sally L Ricketts
Inke R König
Wibke Reinhard
Scott Grundy
H-Erich Wichmann
Phil Barter
Robert Mahley
Y Antero Kesaniemi
Daniel J Rader
Muredach P Reilly
Stephen E Epstein
Alexandre F R Stewart
Cornelia M Van Duijn
Heribert Schunkert
Keith Burling
Panos Deloukas
Tomi Pastinen
Nilesh J Samani
Ruth McPherson
George Davey Smith
Timothy M Frayling
Nicholas J Wareham
James B Meigs
Vincent Mooser
Tim D Spector
GIANT Consortium
author_sort J Brent Richards
title A genome-wide association study reveals variants in ARL15 that influence adiponectin levels.
title_short A genome-wide association study reveals variants in ARL15 that influence adiponectin levels.
title_full A genome-wide association study reveals variants in ARL15 that influence adiponectin levels.
title_fullStr A genome-wide association study reveals variants in ARL15 that influence adiponectin levels.
title_full_unstemmed A genome-wide association study reveals variants in ARL15 that influence adiponectin levels.
title_sort genome-wide association study reveals variants in arl15 that influence adiponectin levels.
publisher Public Library of Science (PLoS)
series PLoS Genetics
issn 1553-7390
1553-7404
publishDate 2009-12-01
description The adipocyte-derived protein adiponectin is highly heritable and inversely associated with risk of type 2 diabetes mellitus (T2D) and coronary heart disease (CHD). We meta-analyzed 3 genome-wide association studies for circulating adiponectin levels (n = 8,531) and sought validation of the lead single nucleotide polymorphisms (SNPs) in 5 additional cohorts (n = 6,202). Five SNPs were genome-wide significant in their relationship with adiponectin (P< or =5x10(-8)). We then tested whether these 5 SNPs were associated with risk of T2D and CHD using a Bonferroni-corrected threshold of P< or =0.011 to declare statistical significance for these disease associations. SNPs at the adiponectin-encoding ADIPOQ locus demonstrated the strongest associations with adiponectin levels (P-combined = 9.2x10(-19) for lead SNP, rs266717, n = 14,733). A novel variant in the ARL15 (ADP-ribosylation factor-like 15) gene was associated with lower circulating levels of adiponectin (rs4311394-G, P-combined = 2.9x10(-8), n = 14,733). This same risk allele at ARL15 was also associated with a higher risk of CHD (odds ratio [OR] = 1.12, P = 8.5x10(-6), n = 22,421) more nominally, an increased risk of T2D (OR = 1.11, P = 3.2x10(-3), n = 10,128), and several metabolic traits. Expression studies in humans indicated that ARL15 is well-expressed in skeletal muscle. These findings identify a novel protein, ARL15, which influences circulating adiponectin levels and may impact upon CHD risk.
url http://europepmc.org/articles/PMC2781107?pdf=render
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