Multiple loci associated with indices of renal function and chronic kidney disease

被引：496

作者：

Koettgen, Anna ^{[3
]}

Glazer, Nicole L. ^{[4
]}

Dehghan, Abbas ^{[6
]}

Hwang, Shih-Jen ^{[1
,2
]}

Katz, Ronit ^{[7
]}

Li, Man ^{[3
]}

Yang, Qiong ^{[8
]}

Gudnason, Vilmundur ^{[9
,10
]}

Launer, Lenore J. ^{[11
]}

Harris, Tamara B. ^{[11
]}

Smith, Albert V. ^{[9
]}

Arking, Dan E. ^{[12
]}

Astor, Brad C. ^{[3
]}

Boerwinkle, Eric ^{[13
,14
]}

Ehret, Georg B. ^{[12
,15
]}

Ruczinski, Ingo ^{[16
]}

Scharpf, Robert B. ^{[16
]}

Chen, Yii-Der Ida ^{[17
]}

de Boer, Ian H. ^{[18
]}

Haritunians, Talin ^{[17
]}

Lumley, Thomas ^{[7
]}

Sarnak, Mark ^{[19
]}

Siscovick, David ^{[5
,20
]}

Benjamin, Emelia J. ^{[21
,22
]}

Levy, Daniel ^{[1
,2
]}

Upadhyay, Ashish ^{[23
]}

Aulchenko, Yurii S. ^{[6
]}

Hofman, Albert ^{[6
]}

Rivadeneira, Fernando ^{[24
]}

Uitterlinden, Andre G. ^{[24
]}

van Duijn, Cornelia M. ^{[6
]}

Chasman, Daniel I. ^{[25
]}

Pare, Guillaume ^{[25
]}

Ridker, Paul M. ^{[25
]}

Kao, W. H. Linda ^{[3
]}

Witteman, Jacqueline C. ^{[6
]}

Coresh, Josef ^{[3
,16
]}

Shlipak, Michael G. ^{[26
]}

Fox, Caroline S. ^{[1
,2
,27
,28
]}

机构：

[1] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA

[2] Ctr Populat Studies, Framingham, MA USA

[3] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA

[4] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, DC USA

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

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

[7] Univ Washington, Dept Biostat, Seattle, WA 98195 USA

[8] Boston Univ, Dept Biostat, Boston, MA 02215 USA

[9] Iceland Heart Assoc Res Inst, Kopavogur, Iceland

[10] Univ Iceland, Reykjavik, Iceland

[11] NIA, Intramural Res Program, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA

[12] Johns Hopkins Med Inst, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA

[13] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA

[14] Univ Texas Hlth Sci Ctr Houston, Div Epidemiol, Houston, TX USA

[15] Univ Hosp Geneva, Div Cardiol, Geneva, Switzerland

[16] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA

[17] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA

[18] Univ Washington, Dept Med, Div Nephrol, Seattle, WA 98195 USA

[19] Tufts Univ New England Med Ctr, Boston, MA USA

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

[21] Boston Univ, Sch Med, Boston, MA 02118 USA

[22] Boston Univ, Sch Publ Hlth, Boston, MA USA

[23] Boston Med Ctr, Renal Sect, Boston, MA USA

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

[25] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA

[26] Univ Calif San Francisco, San Francisco VA Med Ctr, Gen Internal Med Div, San Francisco, CA 94143 USA

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

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

来源：

NATURE GENETICS | 2009年 / 41卷 / 06期

关键词：

GENOME-WIDE ASSOCIATION; SERUM CREATININE; CARDIOVASCULAR-DISEASE; POOLED ANALYSIS; RISK-FACTOR; HEART; GFR; STANNIOCALCIN-1; EPIDEMIOLOGY; HERITABILITY;

D O I：

10.1038/ng.377

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Chronic kidney disease (CKD) has a heritable component and is an important global public health problem because of its high prevalence and morbidity(1). We conducted genome-wide association studies (GWAS) to identify susceptibility loci for glomerular filtration rate, estimated by serum creatinine (eGFRcrea) and cystatin C (eGFRcys), and CKD (eGFRcrea < 60ml/min/1.73 m(2)) in European-ancestry participants of four population-based cohorts (ARIC, CHS, FHS, RS; n = 19,877; 2,388 CKD cases), and tested for replication in 21,466 participants (1,932 CKD cases). We identified significant SNP associations (P < 5 x 10(-8)) with CKD at the UMOD locus, with eGFRcrea at UMOD, SHROOM3 and GATM-SPATA5L1, and with eGFRcys at CST and STC1. UMOD encodes the most common protein in human urine, Tamm-Horsfall protein(2), and rare mutations in UMOD cause mendelian forms of kidney disease(3). Our findings provide new insights into CKD pathogenesis and underscore the importance of common genetic variants influencing renal function and disease.

引用

页码：712 / 717

页数：6

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