Genome-wide association and functional follow-up reveals new loci for kidney function

Cristian Pattaro; Anna Köttgen; Alexander Teumer; Maija Garnaas; Carsten A Böger; Christian Fuchsberger; Matthias Olden; Ming-Huei Chen; Adrienne Tin; Daniel Taliun; Man Li; Xiaoyi Gao; Mathias Gorski; Qiong Yang; Claudia Hundertmark; Meredith C Foster; Conall M O'Seaghdha; Nicole Glazer; Aaron Isaacs; Ching-Ti Liu; Albert V Smith; Jeffrey R O'Connell; Maksim Struchalin; Toshiko Tanaka; Guo Li; Andrew D Johnson; Hinco J Gierman; Mary Feitosa; Shih-Jen Hwang; Elizabeth J Atkinson; Kurt Lohman; Marilyn C Cornelis; Åsa Johansson; Anke Tönjes; Abbas Dehghan; Vincent Chouraki; Elizabeth G Holliday; Rossella Sorice; Zoltan Kutalik; Terho Lehtimäki; Tõnu Esko; Harshal Deshmukh; Sheila Ulivi; Audrey Y Chu; Federico Murgia; Stella Trompet; Medea Imboden; Barbara Kollerits; Giorgio Pistis; Jie Jin Wang; CARDIoGRAM Consortium

doi:10.1371/journal.pgen.1002584

Genome-wide association and functional follow-up reveals new loci for kidney function

Cristian Pattaro^*, Anna Köttgen, Alexander Teumer, Maija Garnaas, Carsten A Böger, Christian Fuchsberger, Matthias Olden, Ming-Huei Chen, Adrienne Tin, Daniel Taliun, Man Li, Xiaoyi Gao, Mathias Gorski, Qiong Yang, Claudia Hundertmark, Meredith C Foster, Conall M O'Seaghdha, Nicole Glazer, Aaron Isaacs, Ching-Ti LiuAlbert V Smith, Jeffrey R O'Connell, Maksim Struchalin, Toshiko Tanaka, Guo Li, Andrew D Johnson, Hinco J Gierman, Mary Feitosa, Shih-Jen Hwang, Elizabeth J Atkinson, Kurt Lohman, Marilyn C Cornelis, Åsa Johansson, Anke Tönjes, Abbas Dehghan, Vincent Chouraki, Elizabeth G Holliday, Rossella Sorice, Zoltan Kutalik, Terho Lehtimäki, Tõnu Esko, Harshal Deshmukh, Sheila Ulivi, Audrey Y Chu, Federico Murgia, Stella Trompet, Medea Imboden, Barbara Kollerits, Giorgio Pistis, Jie Jin Wang, CARDIoGRAM Consortium

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide 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.

Original language	English
Pages (from-to)	e1002584
Journal	Plos Genetics
Volume	8
Issue number	3
DOIs	https://doi.org/10.1371/journal.pgen.1002584
Publication status	Published - 2012
Externally published	Yes

Keywords

ATPases Associated with Diverse Cellular Activities
African Americans/genetics
Aged
Animals
Caspase 9/genetics
Cyclin-Dependent Kinases/genetics
DEAD-box RNA Helicases/genetics
DNA Helicases/genetics
DNA-Binding Proteins
European Continental Ancestry Group/genetics
Female
Follow-Up Studies
Gene Knockdown Techniques
Genome-Wide Association Study
Glomerular Filtration Rate/genetics
Humans
Kidney/physiopathology
Kidney Failure, Chronic/genetics
Male
Middle Aged
Phosphoric Diester Hydrolases/genetics
Zebrafish/genetics

Access to Document

10.1371/journal.pgen.1002584Licence: CC BY

Cite this

Pattaro, C., Köttgen, A., Teumer, A., Garnaas, M., Böger, C. A., Fuchsberger, C., Olden, M., Chen, M.-H., Tin, A., Taliun, D., Li, M., Gao, X., Gorski, M., Yang, Q., Hundertmark, C., Foster, M. C., O'Seaghdha, C. M., Glazer, N., Isaacs, A., ... CARDIoGRAM Consortium (2012). Genome-wide association and functional follow-up reveals new loci for kidney function. Plos Genetics, 8(3), e1002584. https://doi.org/10.1371/journal.pgen.1002584

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title = "Genome-wide association and functional follow-up reveals new loci for kidney function",

abstract = "Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide 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.",

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author = "Cristian Pattaro and Anna K{\"o}ttgen and Alexander Teumer and Maija Garnaas and B{\"o}ger, {Carsten A} and Christian Fuchsberger and Matthias Olden and Ming-Huei Chen and Adrienne Tin and Daniel Taliun and Man Li and Xiaoyi Gao and Mathias Gorski and Qiong Yang and Claudia Hundertmark and Foster, {Meredith C} and O'Seaghdha, {Conall M} and Nicole Glazer and Aaron Isaacs and Ching-Ti Liu and Smith, {Albert V} and O'Connell, {Jeffrey R} and Maksim Struchalin and Toshiko Tanaka and Guo Li and Johnson, {Andrew D} and Gierman, {Hinco J} and Mary Feitosa and Shih-Jen Hwang and Atkinson, {Elizabeth J} and Kurt Lohman and Cornelis, {Marilyn C} and {\AA}sa Johansson and Anke T{\"o}njes and Abbas Dehghan and Vincent Chouraki and Holliday, {Elizabeth G} and Rossella Sorice and Zoltan Kutalik and Terho Lehtim{\"a}ki and T{\~o}nu Esko and Harshal Deshmukh and Sheila Ulivi and Chu, {Audrey Y} and Federico Murgia and Stella Trompet and Medea Imboden and Barbara Kollerits and Giorgio Pistis and Wang, {Jie Jin} and {CARDIoGRAM Consortium}",

year = "2012",

doi = "10.1371/journal.pgen.1002584",

language = "English",

volume = "8",

pages = "e1002584",

journal = "Plos Genetics",

issn = "1553-7390",

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Pattaro, C, Köttgen, A, Teumer, A, Garnaas, M, Böger, CA, Fuchsberger, C, Olden, M, Chen, M-H, Tin, A, Taliun, D, Li, M, Gao, X, Gorski, M, Yang, Q, Hundertmark, C, Foster, MC, O'Seaghdha, CM, Glazer, N, Isaacs, A, Liu, C-T, Smith, AV, O'Connell, JR, Struchalin, M, Tanaka, T, Li, G, Johnson, AD, Gierman, HJ, Feitosa, M, Hwang, S-J, Atkinson, EJ, Lohman, K, Cornelis, MC, Johansson, Å, Tönjes, A, Dehghan, A, Chouraki, V, Holliday, EG, Sorice, R, Kutalik, Z, Lehtimäki, T, Esko, T, Deshmukh, H, Ulivi, S, Chu, AY, Murgia, F, Trompet, S, Imboden, M, Kollerits, B, Pistis, G, Wang, JJ & CARDIoGRAM Consortium 2012, 'Genome-wide association and functional follow-up reveals new loci for kidney function', Plos Genetics, vol. 8, no. 3, pp. e1002584. https://doi.org/10.1371/journal.pgen.1002584

TY - JOUR

T1 - Genome-wide association and functional follow-up reveals new loci for kidney function

AU - Pattaro, Cristian

AU - Köttgen, Anna

AU - Teumer, Alexander

AU - Garnaas, Maija

AU - Böger, Carsten A

AU - Fuchsberger, Christian

AU - Olden, Matthias

AU - Chen, Ming-Huei

AU - Tin, Adrienne

AU - Taliun, Daniel

AU - Li, Man

AU - Gao, Xiaoyi

AU - Gorski, Mathias

AU - Yang, Qiong

AU - Hundertmark, Claudia

AU - Foster, Meredith C

AU - O'Seaghdha, Conall M

AU - Glazer, Nicole

AU - Isaacs, Aaron

AU - Liu, Ching-Ti

AU - Smith, Albert V

AU - O'Connell, Jeffrey R

AU - Struchalin, Maksim

AU - Tanaka, Toshiko

AU - Li, Guo

AU - Johnson, Andrew D

AU - Gierman, Hinco J

AU - Feitosa, Mary

AU - Hwang, Shih-Jen

AU - Atkinson, Elizabeth J

AU - Lohman, Kurt

AU - Cornelis, Marilyn C

AU - Johansson, Åsa

AU - Tönjes, Anke

AU - Dehghan, Abbas

AU - Chouraki, Vincent

AU - Holliday, Elizabeth G

AU - Sorice, Rossella

AU - Kutalik, Zoltan

AU - Lehtimäki, Terho

AU - Esko, Tõnu

AU - Deshmukh, Harshal

AU - Ulivi, Sheila

AU - Chu, Audrey Y

AU - Murgia, Federico

AU - Trompet, Stella

AU - Imboden, Medea

AU - Kollerits, Barbara

AU - Pistis, Giorgio

AU - Wang, Jie Jin

AU - CARDIoGRAM Consortium

PY - 2012

Y1 - 2012

N2 - Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide 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.

AB - Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide 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.

KW - ATPases Associated with Diverse Cellular Activities

KW - African Americans/genetics

KW - Aged

KW - Animals

KW - Caspase 9/genetics

KW - Cyclin-Dependent Kinases/genetics

KW - DEAD-box RNA Helicases/genetics

KW - DNA Helicases/genetics

KW - DNA-Binding Proteins

KW - European Continental Ancestry Group/genetics

KW - Female

KW - Follow-Up Studies

KW - Gene Knockdown Techniques

KW - Genome-Wide Association Study

KW - Glomerular Filtration Rate/genetics

KW - Humans

KW - Kidney/physiopathology

KW - Kidney Failure, Chronic/genetics

KW - Male

KW - Middle Aged

KW - Phosphoric Diester Hydrolases/genetics

KW - Zebrafish/genetics

U2 - 10.1371/journal.pgen.1002584

DO - 10.1371/journal.pgen.1002584

M3 - Article

C2 - 22479191

SN - 1553-7390

VL - 8

SP - e1002584

JO - Plos Genetics

JF - Plos Genetics

IS - 3

ER -