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

C Pattaro; A Kottgen; A Teumer; M Garnaas; CA Boger; C Fuchsberger; M Olden; MH Chen; A Tin; D Taliun; M Li; XY Gao; M Gorski; Q Yang; C Hundertmark; MC Foster; CM O'Seaghdha; N Glazer; Aaron Isaacs; CT Liu; AV Smith; JR O'Connell; M Struchalin; T Tanaka; G (Guo) Li; AD Johnson; HJ Gierman; M Feitosa; SJ Hwang; EJ Atkinson; K Lohman; MC Cornelis; A Johansson; A Tonjes; Abbas Dehghan; V Chouraki; EG Holliday; R Sorice; Z Kutalik; T Lehtimaki; T Esko; H Deshmukh; S Ulivi; AY Chu; F Murgia; S Trompet; M Imboden; B Kollerits; G Pistis; TB Harris; LJ (Lenore) Launer; T Aspelund; G Eiriksdottir; BD Mitchell; E Boerwinkle; Heléna Schmidt; M Cavalieri; M Rao; FB Hu; Ayse Demirkan; Ben Oostra; M de Andrade; ST Turner; JZ (Jing Zhong) Ding; JS Andrews; BI Freedman; W Koenig; T Illig; A Doring; HE Wichmann; I Kolcic; T Zemunik; M Boban; C Minelli; HE Wheeler; W Igl; G Zaboli; SH Wild; AF Wright; H Campbell; D Ellinghaus; U Nothlings; Gunar Jacobs; R Biffar; K Endlich; F Ernst; G Homuth; HK Kroemer; M Nauck; S Stracke; U Volker; H Volzke; P Kovacs; M Stumvoll; R Magi; Bert Hofman; André Uitterlinden; Fernando Rivadeneira; YS Aulchenko; O Polasek; N Hastie; V Vitart; C Helmer; JJ Wang; D Ruggiero; S Bergmann; M Kahonen; J Viikari; T Nikopensius; M Province; S Ketkar; H Colhoun; A Doney; A Robino; F Giulianini; BK Kramer; L Portas; I Ford; BM Buckley; M Adam; GA Thun; B Paulweber; M Haun; C Sala; M Metzger; P Mitchell; M Ciullo; SK Kim; P Vollenweider; O Raitakari; A Metspalu; C Palmer; P Gasparini; M Pirastu; JW Jukema; NM Probst-Hensch; F Kronenberg; D Toniolo; V Gudnason; AR Shuldiner; J Coresh; R Schmidt; L Ferrucci; DS Siscovick; Cornelia Duijn; I Borecki; SLR Kardia; YM Liu; GC Curhan; I Rudan; U Gyllensten; JF Wilson; A Franke; PP Pramstaller; R Rettig; I Prokopenko; JCM Witteman; C Hayward; P Ridker; A Parsa; M Bochud; IM Heid; W Goessling; DI Chasman; WHL Kao; CS Fox

doi:10.1371/journal.pgen.1002584

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

C Pattaro, A Kottgen, A Teumer, M Garnaas, CA Boger, C Fuchsberger, M Olden, MH Chen, A Tin, D Taliun, M Li, XY Gao, M Gorski, Q Yang, C Hundertmark, MC Foster, CM O'Seaghdha, N Glazer, Aaron Isaacs, CT LiuAV Smith, JR O'Connell, M Struchalin, T Tanaka, G (Guo) Li, AD Johnson, HJ Gierman, M Feitosa, SJ Hwang, EJ Atkinson, K Lohman, MC Cornelis, A Johansson, A Tonjes, Abbas Dehghan, V Chouraki, EG Holliday, R Sorice, Z Kutalik, T Lehtimaki, T Esko, H Deshmukh, S Ulivi, AY Chu, F Murgia, S Trompet, M Imboden, B Kollerits, G Pistis, TB Harris, LJ (Lenore) Launer, T Aspelund, G Eiriksdottir, BD Mitchell, E Boerwinkle, Heléna Schmidt, M Cavalieri, M Rao, FB Hu, Ayse Demirkan, Ben Oostra, M de Andrade, ST Turner, JZ (Jing Zhong) Ding, JS Andrews, BI Freedman, W Koenig, T Illig, A Doring, HE Wichmann, I Kolcic, T Zemunik, M Boban, C Minelli, HE Wheeler, W Igl, G Zaboli, SH Wild, AF Wright, H Campbell, D Ellinghaus, U Nothlings, Gunar Jacobs, R Biffar, K Endlich, F Ernst, G Homuth, HK Kroemer, M Nauck, S Stracke, U Volker, H Volzke, P Kovacs, M Stumvoll, R Magi, Bert Hofman, André Uitterlinden, Fernando Rivadeneira, YS Aulchenko, O Polasek, N Hastie, V Vitart, C Helmer, JJ Wang, D Ruggiero, S Bergmann, M Kahonen, J Viikari, T Nikopensius, M Province, S Ketkar, H Colhoun, A Doney, A Robino, F Giulianini, BK Kramer, L Portas, I Ford, BM Buckley, M Adam, GA Thun, B Paulweber, M Haun, C Sala, M Metzger, P Mitchell, M Ciullo, SK Kim, P Vollenweider, O Raitakari, A Metspalu, C Palmer, P Gasparini, M Pirastu, JW Jukema, NM Probst-Hensch, F Kronenberg, D Toniolo, V Gudnason, AR Shuldiner, J Coresh, R Schmidt, L Ferrucci, DS Siscovick, Cornelia Duijn, I Borecki, SLR Kardia, YM Liu, GC Curhan, I Rudan, U Gyllensten, JF Wilson, A Franke, PP Pramstaller, R Rettig, I Prokopenko, JCM Witteman, C Hayward, P Ridker, A Parsa, M Bochud, IM Heid, W Goessling, DI Chasman, WHL Kao, CS Fox

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Abstract

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.

Original language	Undefined/Unknown
Journal	PLoS Genetics (print)
Volume	8
Issue number	3
DOIs	https://doi.org/10.1371/journal.pgen.1002584
Publication status	Published - 2012

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EMC MGC-02-96-01
EMC MM-01-39-09-A
EMC NIHES-01-64-01
EMC NIHES-01-64-02

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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Cite this

Pattaro, C., Kottgen, A., Teumer, A., Garnaas, M., Boger, CA., Fuchsberger, C., Olden, M., Chen, MH., Tin, A., Taliun, D., Li, M., Gao, XY., Gorski, M., Yang, Q., Hundertmark, C., Foster, MC., O'Seaghdha, CM., Glazer, N., Isaacs, A., ... Fox, CS. (2012). Genome-Wide Association and Functional Follow-Up Reveals New Loci for Kidney Function. PLoS Genetics (print), 8(3). https://doi.org/10.1371/journal.pgen.1002584

@article{3195e94f556847d0b86653b792c7a4f2,

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 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.",

author = "C Pattaro and A Kottgen and A Teumer and M Garnaas and CA Boger and C Fuchsberger and M Olden and MH Chen and A Tin and D Taliun and M Li and XY Gao and M Gorski and Q Yang and C Hundertmark and MC Foster and CM O'Seaghdha and N Glazer and Aaron Isaacs and CT Liu and AV Smith and JR O'Connell and M Struchalin and T Tanaka and Li, {G (Guo)} and AD Johnson and HJ Gierman and M Feitosa and SJ Hwang and EJ Atkinson and K Lohman and MC Cornelis and A Johansson and A Tonjes and Abbas Dehghan and V Chouraki and EG Holliday and R Sorice and Z Kutalik and T Lehtimaki and T Esko and H Deshmukh and S Ulivi and AY Chu and F Murgia and S Trompet and M Imboden and B Kollerits and G Pistis and TB Harris and Launer, {LJ (Lenore)} and T Aspelund and G Eiriksdottir and BD Mitchell and E Boerwinkle and Hel{\'e}na Schmidt and M Cavalieri and M Rao and FB Hu and Ayse Demirkan and Ben Oostra and {de Andrade}, M and ST Turner and Ding, {JZ (Jing Zhong)} and JS Andrews and BI Freedman and W Koenig and T Illig and A Doring and HE Wichmann and I Kolcic and T Zemunik and M Boban and C Minelli and HE Wheeler and W Igl and G Zaboli and SH Wild and AF Wright and H Campbell and D Ellinghaus and U Nothlings and Gunar Jacobs and R Biffar and K Endlich and F Ernst and G Homuth and HK Kroemer and M Nauck and S Stracke and U Volker and H Volzke and P Kovacs and M Stumvoll and R Magi and Bert Hofman and Andr{\'e} Uitterlinden and Fernando Rivadeneira and YS Aulchenko and O Polasek and N Hastie and V Vitart and C Helmer and JJ Wang and D Ruggiero and S Bergmann and M Kahonen and J Viikari and T Nikopensius and M Province and S Ketkar and H Colhoun and A Doney and A Robino and F Giulianini and BK Kramer and L Portas and I Ford and BM Buckley and M Adam and GA Thun and B Paulweber and M Haun and C Sala and M Metzger and P Mitchell and M Ciullo and SK Kim and P Vollenweider and O Raitakari and A Metspalu and C Palmer and P Gasparini and M Pirastu and JW Jukema and NM Probst-Hensch and F Kronenberg and D Toniolo and V Gudnason and AR Shuldiner and J Coresh and R Schmidt and L Ferrucci and DS Siscovick and Cornelia Duijn and I Borecki and SLR Kardia and YM Liu and GC Curhan and I Rudan and U Gyllensten and JF Wilson and A Franke and PP Pramstaller and R Rettig and I Prokopenko and JCM Witteman and C Hayward and P Ridker and A Parsa and M Bochud and IM Heid and W Goessling and DI Chasman and WHL Kao and CS Fox",

year = "2012",

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

language = "Undefined/Unknown",

volume = "8",

journal = "PLoS Genetics (print)",

issn = "1553-7390",

publisher = "Public Library of Science",

number = "3",

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Pattaro, C, Kottgen, A, Teumer, A, Garnaas, M, Boger, CA, Fuchsberger, C, Olden, M, Chen, MH, Tin, A, Taliun, D, Li, M, Gao, XY, Gorski, M, Yang, Q, Hundertmark, C, Foster, MC, O'Seaghdha, CM, Glazer, N, Isaacs, A, Liu, CT, Smith, AV, O'Connell, JR, Struchalin, M, Tanaka, T, Li, G, Johnson, AD, Gierman, HJ, Feitosa, M, Hwang, SJ, Atkinson, EJ, Lohman, K, Cornelis, MC, Johansson, A, Tonjes, A, Dehghan, A, Chouraki, V, Holliday, EG, Sorice, R, Kutalik, Z, Lehtimaki, T, Esko, T, Deshmukh, H, Ulivi, S, Chu, AY, Murgia, F, Trompet, S, Imboden, M, Kollerits, B, Pistis, G, Harris, TB, Launer, LJ, Aspelund, T, Eiriksdottir, G, Mitchell, BD, Boerwinkle, E, Schmidt, H, Cavalieri, M, Rao, M, Hu, FB, Demirkan, A, Oostra, B, de Andrade, M, Turner, ST, Ding, JZ, Andrews, JS, Freedman, BI, Koenig, W, Illig, T, Doring, A, Wichmann, HE, Kolcic, I, Zemunik, T, Boban, M, Minelli, C, Wheeler, HE, Igl, W, Zaboli, G, Wild, SH, Wright, AF, Campbell, H, Ellinghaus, D, Nothlings, U, Jacobs, G, Biffar, R, Endlich, K, Ernst, F, Homuth, G, Kroemer, HK, Nauck, M, Stracke, S, Volker, U, Volzke, H, Kovacs, P, Stumvoll, M, Magi, R, Hofman, B , Uitterlinden, A , Rivadeneira, F, Aulchenko, YS, Polasek, O, Hastie, N, Vitart, V, Helmer, C, Wang, JJ, Ruggiero, D, Bergmann, S, Kahonen, M, Viikari, J, Nikopensius, T, Province, M, Ketkar, S, Colhoun, H, Doney, A, Robino, A, Giulianini, F, Kramer, BK, Portas, L, Ford, I, Buckley, BM, Adam, M, Thun, GA, Paulweber, B, Haun, M, Sala, C, Metzger, M, Mitchell, P, Ciullo, M, Kim, SK, Vollenweider, P, Raitakari, O, Metspalu, A, Palmer, C, Gasparini, P, Pirastu, M, Jukema, JW, Probst-Hensch, NM, Kronenberg, F, Toniolo, D, Gudnason, V, Shuldiner, AR, Coresh, J, Schmidt, R, Ferrucci, L, Siscovick, DS, Duijn, C, Borecki, I, Kardia, SLR, Liu, YM, Curhan, GC, Rudan, I, Gyllensten, U, Wilson, JF, Franke, A, Pramstaller, PP, Rettig, R, Prokopenko, I, Witteman, JCM, Hayward, C, Ridker, P, Parsa, A, Bochud, M, Heid, IM, Goessling, W, Chasman, DI, Kao, WHL & Fox, CS 2012, 'Genome-Wide Association and Functional Follow-Up Reveals New Loci for Kidney Function', PLoS Genetics (print), vol. 8, no. 3. 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, C

AU - Kottgen, A

AU - Teumer, A

AU - Garnaas, M

AU - Boger, CA

AU - Fuchsberger, C

AU - Olden, M

AU - Chen, MH

AU - Tin, A

AU - Taliun, D

AU - Li, M

AU - Gao, XY

AU - Gorski, M

AU - Yang, Q

AU - Hundertmark, C

AU - Foster, MC

AU - O'Seaghdha, CM

AU - Glazer, N

AU - Isaacs, Aaron

AU - Liu, CT

AU - Smith, AV

AU - O'Connell, JR

AU - Struchalin, M

AU - Tanaka, T

AU - Li, G (Guo)

AU - Johnson, AD

AU - Gierman, HJ

AU - Feitosa, M

AU - Hwang, SJ

AU - Atkinson, EJ

AU - Lohman, K

AU - Cornelis, MC

AU - Johansson, A

AU - Tonjes, A

AU - Dehghan, Abbas

AU - Chouraki, V

AU - Holliday, EG

AU - Sorice, R

AU - Kutalik, Z

AU - Lehtimaki, T

AU - Esko, T

AU - Deshmukh, H

AU - Ulivi, S

AU - Chu, AY

AU - Murgia, F

AU - Trompet, S

AU - Imboden, M

AU - Kollerits, B

AU - Pistis, G

AU - Harris, TB

AU - Launer, LJ (Lenore)

AU - Aspelund, T

AU - Eiriksdottir, G

AU - Mitchell, BD

AU - Boerwinkle, E

AU - Schmidt, Heléna

AU - Cavalieri, M

AU - Rao, M

AU - Hu, FB

AU - Demirkan, Ayse

AU - Oostra, Ben

AU - de Andrade, M

AU - Turner, ST

AU - Ding, JZ (Jing Zhong)

AU - Andrews, JS

AU - Freedman, BI

AU - Koenig, W

AU - Illig, T

AU - Doring, A

AU - Wichmann, HE

AU - Kolcic, I

AU - Zemunik, T

AU - Boban, M

AU - Minelli, C

AU - Wheeler, HE

AU - Igl, W

AU - Zaboli, G

AU - Wild, SH

AU - Wright, AF

AU - Campbell, H

AU - Ellinghaus, D

AU - Nothlings, U

AU - Jacobs, Gunar

AU - Biffar, R

AU - Endlich, K

AU - Ernst, F

AU - Homuth, G

AU - Kroemer, HK

AU - Nauck, M

AU - Stracke, S

AU - Volker, U

AU - Volzke, H

AU - Kovacs, P

AU - Stumvoll, M

AU - Magi, R

AU - Hofman, Bert

AU - Uitterlinden, André

AU - Rivadeneira, Fernando

AU - Aulchenko, YS

AU - Polasek, O

AU - Hastie, N

AU - Vitart, V

AU - Helmer, C

AU - Wang, JJ

AU - Ruggiero, D

AU - Bergmann, S

AU - Kahonen, M

AU - Viikari, J

AU - Nikopensius, T

AU - Province, M

AU - Ketkar, S

AU - Colhoun, H

AU - Doney, A

AU - Robino, A

AU - Giulianini, F

AU - Kramer, BK

AU - Portas, L

AU - Ford, I

AU - Buckley, BM

AU - Adam, M

AU - Thun, GA

AU - Paulweber, B

AU - Haun, M

AU - Sala, C

AU - Metzger, M

AU - Mitchell, P

AU - Ciullo, M

AU - Kim, SK

AU - Vollenweider, P

AU - Raitakari, O

AU - Metspalu, A

AU - Palmer, C

AU - Gasparini, P

AU - Pirastu, M

AU - Jukema, JW

AU - Probst-Hensch, NM

AU - Kronenberg, F

AU - Toniolo, D

AU - Gudnason, V

AU - Shuldiner, AR

AU - Coresh, J

AU - Schmidt, R

AU - Ferrucci, L

AU - Siscovick, DS

AU - Duijn, Cornelia

AU - Borecki, I

AU - Kardia, SLR

AU - Liu, YM

AU - Curhan, GC

AU - Rudan, I

AU - Gyllensten, U

AU - Wilson, JF

AU - Franke, A

AU - Pramstaller, PP

AU - Rettig, R

AU - Prokopenko, I

AU - Witteman, JCM

AU - Hayward, C

AU - Ridker, P

AU - Parsa, A

AU - Bochud, M

AU - Heid, IM

AU - Goessling, W

AU - Chasman, DI

AU - Kao, WHL

AU - Fox, CS

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

U2 - 10.1371/journal.pgen.1002584

DO - 10.1371/journal.pgen.1002584

M3 - Article

C2 - 22479191

SN - 1553-7390

VL - 8

JO - PLoS Genetics (print)

JF - PLoS Genetics (print)

IS - 3

ER -