Clear detection of ADIPOQ locus as the major gene for plasma adiponectin: Results of genome-wide association analyses including 4659 European individuals

被引：131

作者：

Heid, Iris M. ^{[2
,3
]}

Henneman, Peter ^{[4
]}

Hicks, Andrew ^{[5
]}

Coassin, Stefan ^{[1
]}

Winkler, Thomas ^{[2
]}

Aulchenko, Yurii S. ^{[6
]}

Fuchsberger, Christian ^{[5
]}

Song, Kijoung ^{[7
]}

Hivert, Marie-France ^{[8
]}

Waterworth, Dawn M. ^{[7
]}

Timpson, Nicholas J. ^{[9
]}

Richards, J. Brent ^{[10
,11
,12
]}

Perry, John R. B. ^{[13
]}

Tanaka, Toshiko ^{[14
,15
]}

Amin, Najaf ^{[4
]}

Kollerits, Barbara ^{[1
]}

Pichler, Irene ^{[5
]}

Oostra, Ben A. ^{[6
]}

Thorand, Barbara ^{[3
]}

Frants, Rune R. ^{[4
]}

Illig, Thomas ^{[3
]}

Dupuis, Josee ^{[16
,17
]}

Glaser, Beate ^{[9
]}

Spector, Tim ^{[12
]}

Guralnik, Jack ^{[18
]}

Egan, Josephine M. ^{[19
]}

Florez, Jose C. ^{[20
,21
,22
,23
]}

Evans, David M. ^{[9
]}

Soranzo, Nicole ^{[12
,24
]}

Bandinelli, Stefania ^{[25
]}

Carlson, Olga D. ^{[19
]}

Frayling, Timothy M. ^{[13
]}

Burling, Keith ^{[26
]}

Smith, George Davey ^{[9
]}

Mooser, Vincent ^{[7
]}

Ferrucci, Luigi ^{[15
]}

Meigs, James B. ^{[20
,27
]}

Vollenweider, Peter ^{[28
]}

van Dijk, Ko Willems ^{[4
,29
]}

Pramstaller, Peter ^{[5
,30
,31
]}

Kronenberg, Florian ^{[1
]}

van Duijn, Cornelia M. ^{[4
]}

机构：

[1] Innsbruck Med Univ, Div Genet Epidemiol, Dept Med Genet Mol & Clin Pharmacol, Innsbruck, Austria

[2] Univ Regensburg, Med Ctr, Dept Epidemiol & Prevent Med, Regensburg, Germany

[3] German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Epidemiol, Neuherberg, Germany

[4] Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands

[5] European Acad Bozen Bolzano EURAC, Inst Med Genet, Bolzano, Italy

[6] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands

[7] GlaxoSmithKline, Div Genet, King Of Prussia, PA USA

[8] Univ Sherbrooke, Serv Endocrinol, Dept Med, Quebec City, PQ, Canada

[9] Univ Bristol, Dept Social Med, MRC, Ctr Causal Anal Translat Epidemiol, Bristol BS8 2BN, Avon, England

[10] McGill Univ, Dept Med, Montreal, PQ H3T 1E2, Canada

[11] McGill Univ, Dept Human Genet, Montreal, PQ H3T 1E2, Canada

[12] Kings Coll London, London SE1 7EH, England

[13] Peninsula Med Sch, Exeter, Devon, England

[14] Medstar Res Inst, Baltimore, MD USA

[15] NIA, Clin Res Branch, Baltimore, MD 21224 USA

[16] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA

[17] NHLBI, Framingham Heart Study, Framingham, MA USA

[18] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA

[19] NIA, Clin Invest Lab, Baltimore, MD 21224 USA

[20] Harvard Univ, Sch Med, Dept Med, Boston, MA USA

[21] Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA

[22] Massachusetts Gen Hosp, Dept Med, Diabet Unit, Boston, MA 02114 USA

[23] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA

[24] Wellcome Trust Sanger Inst, Hinxton, England

[25] ASF, Geriatr Rehabil Unit, Florence, Italy

[26] Univ Cambridge, Addenbrookes Hosp, Inst Metab Sci, Metab Res Labs, Cambridge CB2 0QQ, England

[27] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA

[28] CHU Vaudois, Dept Internal Med, CH-1011 Lausanne, Switzerland

[29] Leiden Univ, Med Ctr, Dept Internal Med, Leiden, Netherlands

[30] Gen Cent Hosp, Dept Neurol, Bolzano, Italy

[31] Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany

来源：

ATHEROSCLEROSIS | 2010年 / 208卷 / 02期

基金：

英国医学研究理事会;

关键词：

Adiponectin; Genome-wide association study; Polymorphism; Cardiovascular disease; Metabolic syndrome; METABOLIC SYNDROME; INSULIN-RESISTANCE; APM1; GENE; RISK; PROMOTER; DISEASE; OBESITY; PREVALENCE; CAUCASIANS; CONTRIBUTE;

D O I：

10.1016/j.atherosclerosis.2009.11.035

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective: Plasma adiponectin is strongly associated with various components of metabolic syndrome, type 2 diabetes and cardiovascular outcomes. Concentrations are highly heritable and differ between men and women. We therefore aimed to investigate the genetics of plasma adiponectin in men and women. Methods: Wecombined genome-wide association scans of three population-based studies including 4659 persons. For the replication stage in 13795 subjects, we selected the 20 top signals of the combined analysis, as well as the 10 top signals with p-values less than 1.0 x 10(-4) for each the men-and the women-specific analyses. We further selected 73 SNPs that were consistently associated with metabolic syndrome parameters in previous genome-wide association studies to check for their association with plasma adiponectin. Results: The ADIPOQ locus showed genome-wide significant p-values in the combined (p = 4.3 x 10(-24)) as well as in both women-and men-specific analyses (p = 8.7 x 10(-17) and p = 2.5 x 10(-11), respectively). None of the other 39 top signal SNPs showed evidence for association in the replication analysis. None of 73 SNPs from metabolic syndrome loci e x hibited association with plasma adiponectin (p > 0.01). Conclusions: We demonstrated the ADIPOQ gene as the only major gene for plasma adiponectin, which e x plains 6.7% of the phenotypic variance. We further found that neither this gene nor any of the metabolic syndrome loci e x plained the se x differences observed for plasma adiponectin. Larger studies are needed to identify more moderate genetic determinants of plasma adiponectin. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

引用

页码：412 / 420

页数：9

共 34 条

[1] Adiponectin: from obesity to cardiovascular disease [J].

Antoniades, C. ;

Antonopoulos, A. S. ;

Tousoulis, D. ;

Stefanadis, C. .

OBESITY REVIEWS, 2009, 10 (03) :269-279

[2] GenABEL: an R library for genome-wide association analysis [J].

Aulchenko, Yurii S. ;

Ripke, Stephan ;

Isaacs, Aaron ;

Van Duijn, Cornelia M. .

BIOINFORMATICS, 2007, 23 (10) :1294-1296

[3] Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts [J].

Aulchenko, Yurii S. ;

Ripatti, Samuli ;

Lindqvist, Ida ;

Boomsma, Dorret ;

Heid, Iris M. ;

Pramstaller, Peter P. ;

Penninx, Brenda W. J. H. ;

Janssens, A. Cecile J. W. ;

Wilson, James F. ;

Spector, Tim ;

Martin, Nicholas G. ;

Pedersen, Nancy L. ;

Kyvik, Kirsten Ohm ;

Kaprio, Jaakko ;

Hofman, Albert ;

Freimer, Nelson B. ;

Jarvelin, Marjo-Riitta ;

Gyllensten, Ulf ;

Campbell, Harry ;

Rudan, Igor ;

Johansson, Asa ;

Marroni, Fabio ;

Hayward, Caroline ;

Vitart, Veronique ;

Jonasson, Inger ;

Pattaro, Cristian ;

Wright, Alan ;

Hastie, Nick ;

Pichler, Irene ;

Hicks, Andrew A. ;

Falchi, Mario ;

Willemsen, Gonneke ;

Hottenga, Jouke-Jan ;

de Geus, Eco J. C. ;

Montgomery, Grant W. ;

Whitfield, John ;

Magnusson, Patrik ;

Saharinen, Juha ;

Perola, Markus ;

Silander, Kaisa ;

Isaacs, Aaron ;

Sijbrands, Eric J. G. ;

Uitterlinden, Andre G. ;

Witteman, Jacqueline C. M. ;

Oostra, Ben A. ;

Elliott, Paul ;

Ruokonen, Aimo ;

Sabatti, Chiara ;

Gieger, Christian ;

Meitinger, Thomas .

NATURE GENETICS, 2009, 41 (01) :47-55

[4] The adipocyte-secreted protein Acrp30 enhances hepatic insulin action [J].

Berg, AH ;

Combs, TP ;

Du, XL ;

Brownlee, M ;

Scherer, PE .

NATURE MEDICINE, 2001, 7 (08) :947-953

[5]

COASSIN S, ATHEROSCLER IN PRESS

[6] Multiple rare Alleles contribute to low plasma levels of HDL cholesterol [J].

Cohen, JC ;

Kiss, RS ;

Pertsemlidis, A ;

Marcel, YL ;

McPherson, R ;

Hobbs, HH .

SCIENCE, 2004, 305 (5685) :869-872

[7] The genetic basis of plasma variation in adiponectin, a global endophenotype for obesity and the metabolic syndrome [J].

Comuzzie, AG ;

Funahashi, T ;

Sonnenberg, G ;

Martin, LJ ;

Jacob, HJ ;

Black, AEK ;

Maas, D ;

Takahashi, M ;

Kihara, S ;

Tanaka, S ;

Matsuzawa, Y ;

Blangero, J ;

Cohen, D ;

Kissebah, A .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2001, 86 (09) :4321-4325

[8] Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association study [J].

Dehghan, Abbas ;

Kottgen, Anna ;

Yang, Qiong ;

Hwang, Shih Jen ;

Kao, W. H. Linda ;

Rivadeneira, Fernando ;

Boerwinkle, Eric ;

Levy, Daniel ;

Hofman, Albert ;

Astor, Brad C. ;

Benjamin, Emelia J. ;

van Duijn, Cornelia M. ;

Witteman, Jacqueline C. ;

Coresh, Josef ;

Fox, Caroline S. .

LANCET, 2008, 372 (9654) :1953-1961

[9] SLC2A9 influences uric acid concentrations with pronounced sex-specific effects [J].

Doering, Angela ;

Gieger, Christian ;

Mehta, Divya ;

Gohlke, Henning ;

Prokisch, Holger ;

Coassin, Stefan ;

Fischer, Guido ;

Henke, Kathleen ;

Klopp, Norman ;

Kronenberg, Florian ;

Paulweber, Bernhard ;

Pfeufer, Arne ;

Rosskopf, Dieter ;

Voelzke, Henry ;

Illig, Thomas ;

Meitinger, Thomas ;

Wichmann, H-Erich ;

Meisinger, Christa .

NATURE GENETICS, 2008, 40 (04) :430-436

[10] Sexual dimorphism in environmental epigenetic programming [J].

Gabory, Anne ;

Attig, Linda ;

Junien, Claudine .

MOLECULAR AND CELLULAR ENDOCRINOLOGY, 2009, 304 (1-2) :8-18

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