Association of eGFR-Related Loci Identified by GWAS with Incident CKD and ESRD

被引：165

作者：

Boeger, Carsten A. ^{[1
]}

Gorski, Mathias ^{[2
,3
]}

Li, Man ^{[4
]}

Hoffmann, Michael M. ^{[5
]}

Huang, Chunmei ^{[6
]}

Yang, Qiong ^{[7
]}

Teumer, Alexander ^{[8
]}

Krane, Vera ^{[9
]}

O'Seaghdha, Conall M. ^{[10
,11
,12
,13
]}

Kutalik, Zoltan ^{[14
,15
]}

Wichmann, H. -Erich ^{[3
,16
,17
]}

Haak, Thomas ^{[18
]}

Boes, Eva ^{[19
]}

Coassin, Stefan ^{[19
]}

Coresh, Josef ^{[20
,21
]}

Kollerits, Barbara ^{[19
]}

Haun, Margot ^{[19
]}

Paulweber, Bernhard ^{[22
]}

Koettgen, Anna ^{[4
,23
]}

Li, Guo ^{[24
]}

Shlipak, Michael G. ^{[25
,26
]}

Powe, Neil ^{[27
]}

Hwang, Shih-Jen ^{[12
,13
]}

Dehghan, Abbas ^{[28
]}

Rivadeneira, Fernando ^{[29
]}

Uitterlinden, Andre ^{[29
]}

Hofman, Albert ^{[28
]}

Beckmann, Jacques S. ^{[30
,31
]}

Kraemer, Bernhard K. ^{[32
]}

Witteman, Jacqueline ^{[28
]}

Bochud, Murielle ^{[33
]}

Siscovick, David ^{[34
,35
]}

Rettig, Rainer ^{[36
]}

Kronenberg, Florian ^{[19
]}

Wanner, Christoph ^{[9
]}

Thadhani, Ravi I. ^{[6
]}

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

Fox, Caroline S. ^{[11
,12
,13
,37
]}

Kao, W. H. ^{[20
,21
]}

机构：

[1] Univ Hosp Regensburg, Dept Internal Med 2, Regensburg, Germany

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

[3] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 1, Neuherberg, Germany

[4] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA

[5] Univ Freiburg, Univ Med Ctr Freiburg, Freiburg, Germany

[6] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA

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

[8] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany

[9] Univ Wurzburg, Div Nephrol, Dept Med 1, Univ Hosp Wurzburg, Wurzburg, Germany

[10] Brigham & Womens Hosp, Div Nephrol, Boston, MA 02115 USA

[11] Harvard Univ, Sch Med, Boston, MA USA

[12] NHLBIs Framingham Heart Study, Framingham, MA USA

[13] Ctr Populat Studies, Framingham, MA USA

[14] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland

[15] Swiss Inst Bioinformat, Lausanne, Switzerland

[16] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany

[17] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany

[18] Diabet Klin Bad Mergentheim, Bad Mergentheim, Germany

[19] Innsbruck Med Univ, Div Genet Epidemiol, Innsbruck, Austria

[20] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA

[21] Johns Hopkins Bloomberg Sch Publ Hlth, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA

[22] Paracelsus Med Univ, Dept Internal Med 1, Salzburg, Austria

[23] Univ Hosp Freiburg, Div Renal, Freiburg, Germany

[24] Univ Washington, Dept Med, Seattle, WA USA

[25] San Francisco VA Med Ctr, Div Gen Internal Med, San Francisco, CA USA

[26] Univ Calif San Francisco, Dept Med Epidemiol & Biostat, San Francisco, CA 94143 USA

[27] San Francisco Gen Hosp, Dept Med, San Francisco, CA 94110 USA

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

[29] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands

[30] CHU Vaudois, Serv Med Genet, CH-1011 Lausanne, Switzerland

[31] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland

[32] Univ Med Ctr Mannheim, Dept Med 5, Mannheim, Germany

[33] CHU Vaudois, Univ Inst Social & Prevent Med, CH-1011 Lausanne, Switzerland

[34] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA

[35] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA

[36] Ernst Moritz Arndt Univ Greifswald, Inst Physiol, Greifswald, Germany

[37] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA

来源：

PLOS GENETICS | 2011年 / 7卷 / 09期

基金：

瑞士国家科学基金会; 美国国家卫生研究院;

关键词：

CHRONIC KIDNEY-DISEASE; STAGE RENAL-DISEASE; DIABETIC-NEPHROPATHY; RISK; PROGRESSION; GENE; MORTALITY; VARIANTS; SUSCEPTIBILITY; DECLINE;

D O I：

10.1371/journal.pgen.1002292

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Family studies suggest a genetic component to the etiology of chronic kidney disease (CKD) and end stage renal disease (ESRD). Previously, we identified 16 loci for eGFR in genome-wide association studies, but the associations of these single nucleotide polymorphisms (SNPs) for incident CKD or ESRD are unknown. We thus investigated the association of these loci with incident CKD in 26,308 individuals of European ancestry free of CKD at baseline drawn from eight population-based cohorts followed for a median of 7.2 years (including 2,122 incident CKD cases defined as eGFR < 60ml/min/1.73m(2) at follow-up) and with ESRD in four case-control studies in subjects of European ancestry (3,775 cases, 4,577 controls). SNPs at 11 of the 16 loci (UMOD, PRKAG2, ANXA9, DAB2, SHROOM3, DACH1, STC1, SLC34A1, ALMS1/NAT8, UBE2Q2, and GCKR) were associated with incident CKD; p-values ranged from p = 4.1e-9 in UMOD to p = 0.03 in GCKR. After adjusting for baseline eGFR, six of these loci remained significantly associated with incident CKD (UMOD, PRKAG2, ANXA9, DAB2, DACH1, and STC1). SNPs in UMOD (OR = 0.92, p = 0.04) and GCKR (OR = 0.93, p = 0.03) were nominally associated with ESRD. In summary, the majority of eGFR-related loci are either associated or show a strong trend towards association with incident CKD, but have modest associations with ESRD in individuals of European descent. Additional work is required to characterize the association of genetic determinants of CKD and ESRD at different stages of disease progression.

引用

页数：8

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