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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Format: | Article |
Language: | English |
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Public Library of Science (PLoS)
2009-12-01
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Series: | PLoS Genetics |
Online Access: | http://europepmc.org/articles/PMC2781107?pdf=render |
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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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