Genome-Wide Association and Functional Follow-Up Reveals New Loci for Kidney Function

被引：163

作者：

Pattaro, Cristian ^{[1
,2
]}

Koettgen, Anna ^{[3
,4
]}

Teumer, Alexander ^{[5
]}

Garnaas, Maija ^{[6
]}

Boeger, Carsten A. ^{[7
]}

Fuchsberger, Christian ^{[8
]}

Olden, Matthias ^{[9
,10
]}

Chen, Ming-Huei ^{[11
,12
]}

Tin, Adrienne ^{[3
]}

Taliun, Daniel ^{[1
,2
]}

Li, Man ^{[3
]}

Gao, Xiaoyi ^{[13
]}

Gorski, Mathias ^{[14
,15
]}

Yang, Qiong ^{[12
]}

Hundertmark, Claudia ^{[4
]}

Foster, Meredith C. ^{[16
,17
]}

O'Seaghdha, Conall M. ^{[16
,17
,18
]}

Glazer, Nicole ^{[20
]}

Isaacs, Aaron ^{[21
,22
]}

Liu, Ching-Ti ^{[12
]}

Smith, Albert V. ^{[23
,24
]}

O'Connell, Jeffrey R. ^{[25
]}

Struchalin, Maksim ^{[26
,27
]}

Tanaka, Toshiko ^{[28
]}

Li, Guo ^{[29
]}

Johnson, Andrew D. ^{[16
,17
]}

Gierman, Hinco J. ^{[30
]}

Feitosa, Mary ^{[13
]}

Hwang, Shih-Jen ^{[16
,17
]}

Atkinson, Elizabeth J. ^{[31
]}

Lohman, Kurt ^{[32
]}

Cornelis, Marilyn C. ^{[33
]}

Johansson, Asa ^{[34
]}

Toenjes, Anke ^{[35
,36
]}

Dehghan, Abbas

Chouraki, Vincent ^{[37
]}

Holliday, Elizabeth G. ^{[38
,39
]}

Sorice, Rossella ^{[40
]}

Kutalik, Zoltan ^{[41
,42
]}

Lehtimaeki, Terho ^{[43
,44
]}

Esko, Tonu ^{[45
,46
,47
]}

Deshmukh, Harshal

Ulivi, Sheila ^{[49
]}

Chu, Audrey Y.

Murgia, Federico ^{[50
]}

Trompet, Stella ^{[51
]}

Imboden, Medea ^{[52
]}

Kollerits, Barbara ^{[53
]}

Pistis, Giorgio ^{[54
]}

Harris, Tamara B. ^{[55
]}

机构：

[1] Univ Lubeck, European Acad Bozen Bolzano EURAC, Inst Med Genet, Bolzano, Italy

[2] Univ Lubeck, Affiliated Inst, Bolzano, Italy

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

[4] Freiburg Univ Clin, Div Renal, Freiburg, Germany

[5] Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany

[6] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Genet, Boston, MA 02115 USA

[7] Univ Med Ctr Regensburg, Dept Internal Med 2, Regensburg, Germany

[8] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA

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

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

[11] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA

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

[13] Washington Univ, Sch Med, Div Stat Genom, St Louis, MO USA

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

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

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

[17] Ctr Populat Studies, Framingham, MA USA

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

[19] Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA

[20] Boston Univ, Sch Med, Dept Med, Sect Prevent Med & Epidemiol, Boston, MA 02118 USA

[21] Erasmus Univ, Med Ctr, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands

[22] Ctr Med Syst Biol, Leiden, Netherlands

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

[24] Univ Iceland, Reykjavik, Iceland

[25] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA

[26] Erasmus Univ, Dept Epidemiol & Biostat, Med Ctr, NL-3000 DR Rotterdam, Netherlands

[27] Erasmus Univ, Dept Forens Mol Biol, Med Ctr, Rotterdam, Netherlands

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

[29] Univ Washington, Seattle, WA 98195 USA

[30] Stanford Univ, Dept Dev Biol, Stanford, CA 94305 USA

[31] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN USA

[32] Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA

[33] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA

[34] Uppsala Univ, Rudbeck Lab, Uppsala, Sweden

[35] Univ Leipzig, Dept Med, Leipzig, Germany

[36] Univ Leipzig, IFB Adipos Dis, Leipzig, Germany

[37] Inst Pasteur, Inserm UMR744, F-59019 Lille, France

[38] Univ Newcastle, Sch Med & Publ Hlth, Ctr Clin Epidemiol & Biostat, Newcastle, NSW 2300, Australia

[39] Hunter Med Res Inst, Ctr Informat Based Med, Newcastle, NSW, Australia

[40] Inst Genet & Biophys Adriano Buzzati Traverso CNR, Naples, Italy

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

[42] Swiss Inst Bioinformat, Lausanne, Switzerland

[43] Univ Tampere, Dept Clin Chem, FIN-33101 Tampere, Finland

[44] Tampere Univ Hosp, Ctr Lab Med Tampere Finn Medi 2, Tampere, Finland

[45] EGCUT, Tartu, Estonia

[46] Univ Tartu, Estonian Bioctr, EE-50090 Tartu, Estonia

[47] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia

[48] Univ Dundee, Clin Res Ctr, Ninewells Hosp, Wellcome Trust Ctr Mol Med,NHS Tayside, Dundee, Scotland

[49] Inst Maternal & Child Hlth IRCCS Burlo Garofo, Trieste, Italy

[50] Inst Populat Genet CNR, Sassari, Italy

来源：

PLOS GENETICS | 2012年 / 8卷 / 03期

基金：

奥地利科学基金会; 英国医学研究理事会; 英国惠康基金; 芬兰科学院; 美国国家卫生研究院; 瑞士国家科学基金会;

关键词：

GLOMERULAR-FILTRATION-RATE; GENE-EXPRESSION; SERUM CREATININE; COLLABORATIVE METAANALYSIS; HIGHER ALBUMINURIA; DISEASE; ZEBRAFISH; ORGANIZATION; BRAIN; GFR;

D O I：

10.1371/journal.pgen.1002584

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genomewide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.

引用

页数：15

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