Common variants in mendelian kidney disease genes and their association with renal function

Afshin Parsa; Christian Fuchsberger; Anna Köttgen; Conall M. O'Seaghdha; Cristian Pattaro; Mariza De Andrade; Daniel I. Chasman; Alexander Teumer; Karlhans Endlich; Matthias Olden; Ming Huei Chen; Adrienne Tin; Young J. Kim; Daniel Taliun; Man Li; Mary Feitosa; Mathias Gorski; Qiong Yang; Claudia Hundertmark; Meredith C. Foster; Nicole Glazer; Aaron Isaacs; Madhumathi Rao; Albert V. Smith; Jeffrey R. O'Connell; Maksim Struchalin; Toshiko Tanaka; Guo Li; Shih Jen Hwang; Elizabeth J. Atkinson; Kurt Lohman; Marilyn C. Cornelis; Asa Johansson; Anke Tönjes; Abbas Dehghan; Vincent Couraki; 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; Tamara B. Harris; Lenore J. Launer; Thor Aspelund; Gudny Eiriksdottir; Braxton D. Mitchell; Eric Boerwinkle; Helena Schmidt; Edith Hofer; Frank Hu; Ayse Demirkan; Ben A. Oostra; Stephen T. Turner; Jingzhong Ding; Jeanette S. Andrews; Barry I. Freedman; Franco Giulianini; Wolfgang Koenig; Thomas Illig; Angela Döring; H. Erich Wichmann; Lina Zgaga; Tatijana Zemunik; Mladen Boban; Cosetta Minelli; Heather E. Wheeler; Wilmar Igl; Ghazal Zaboli; Sarah H. Wild; Alan F. Wright; Harry Campbell; David Ellinghaus; Ute Nöthlings; Gunnar Jacobs; Reiner Biffar; Florian Ernst; Georg Homuth; Heyo K. Kroemer; Matthias Nauck; Sylvia Stracke; Uwe Völker; Henry Völzke; Peter Kovacs; Michael Stumvoll; Reedik Mägi; Albert Hofman; Andre G. Uitterlinden; Fernando Rivadeneira; Yurii S. Aulchenko; Ozren Polasek; Nick Hastie; Veronique Vitart; Catherine Helmer; Jie Jin Wang; Bénédicte Stengel; Daniela Ruggiero; Sven Bergmann; Mika Kähönen; Jorma Viikari; Tiit Nikopensius; Michael Province; Helen Colhoun; Alex Doney; Antonietta Robino; Bernhard K. Krämer; Laura Portas; Ian Ford; Brendan M. Buckley; Martin Adam; Gian Andri Thun; Bernhard Paulweber; Margot Haun; Cinzia Sala; Paul Mitchell; Marina Ciullo; Peter Vollenweider; Olli Raitakari; Andres Metspalu; Colin Palmer; Paolo Gasparini; Mario Pirastu; J. Wouter Jukema; Nicole M. Probst-Hensch; Florian Kronenberg; Daniela Toniolo; Vilmundur Gudnason; Alan R. Shuldiner; Josef Coresh; Reinhold Schmidt; Luigi Ferrucci; Cornelia M. Van Duijn; Ingrid Borecki; Sharon L.R. Kardia; Yongmei Liu; Gary C. Curhan; Igor Rudan; Ulf Gyllensten; James F. Wilson; Andre Franke; Peter P. Pramstaller; Rainer Rettig; Inga Prokopenko; Jacqueline Witteman; Caroline Hayward; Paul M. Ridker; Murielle Bochud; Iris M. Heid; David S. Siscovick; Caroline S. Fox; W. Linda Kao; Carsten A. Böger

doi:10.1681/ASN.2012100983

Common variants in mendelian kidney disease genes and their association with renal function

Afshin Parsa, Christian Fuchsberger, Anna Köttgen, Conall M. O'Seaghdha, Cristian Pattaro, Mariza De Andrade, Daniel I. Chasman, Alexander Teumer, Karlhans Endlich, Matthias Olden, Ming Huei Chen, Adrienne Tin, Young J. Kim, Daniel Taliun, Man Li, Mary Feitosa, Mathias Gorski, Qiong Yang, Claudia Hundertmark, Meredith C. FosterNicole Glazer, Aaron Isaacs, Madhumathi Rao, Albert V. Smith, Jeffrey R. O'Connell, Maksim Struchalin, Toshiko Tanaka, Guo Li, Shih Jen Hwang, Elizabeth J. Atkinson, Kurt Lohman, Marilyn C. Cornelis, Asa Johansson, Anke Tönjes, Abbas Dehghan, Vincent Couraki, 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, Tamara B. Harris, Lenore J. Launer, Thor Aspelund, Gudny Eiriksdottir, Braxton D. Mitchell, Eric Boerwinkle, Helena Schmidt, Edith Hofer, Frank Hu, Ayse Demirkan, Ben A. Oostra, Stephen T. Turner, Jingzhong Ding, Jeanette S. Andrews, Barry I. Freedman, Franco Giulianini, Wolfgang Koenig, Thomas Illig, Angela Döring, H. Erich Wichmann, Lina Zgaga, Tatijana Zemunik, Mladen Boban, Cosetta Minelli, Heather E. Wheeler, Wilmar Igl, Ghazal Zaboli, Sarah H. Wild, Alan F. Wright, Harry Campbell, David Ellinghaus, Ute Nöthlings, Gunnar Jacobs, Reiner Biffar, Florian Ernst, Georg Homuth, Heyo K. Kroemer, Matthias Nauck, Sylvia Stracke, Uwe Völker, Henry Völzke, Peter Kovacs, Michael Stumvoll, Reedik Mägi, Albert Hofman, Andre G. Uitterlinden, Fernando Rivadeneira, Yurii S. Aulchenko, Ozren Polasek, Nick Hastie, Veronique Vitart, Catherine Helmer, Jie Jin Wang, Bénédicte Stengel, Daniela Ruggiero, Sven Bergmann, Mika Kähönen, Jorma Viikari, Tiit Nikopensius, Michael Province, Helen Colhoun, Alex Doney, Antonietta Robino, Bernhard K. Krämer, Laura Portas, Ian Ford, Brendan M. Buckley, Martin Adam, Gian Andri Thun, Bernhard Paulweber, Margot Haun, Cinzia Sala, Paul Mitchell, Marina Ciullo, Peter Vollenweider, Olli Raitakari, Andres Metspalu, Colin Palmer, Paolo Gasparini, Mario Pirastu, J. Wouter Jukema, Nicole M. Probst-Hensch, Florian Kronenberg, Daniela Toniolo, Vilmundur Gudnason, Alan R. Shuldiner, Josef Coresh, Reinhold Schmidt, Luigi Ferrucci, Cornelia M. Van Duijn, Ingrid Borecki, Sharon L.R. Kardia, Yongmei Liu, Gary C. Curhan, Igor Rudan, Ulf Gyllensten, James F. Wilson, Andre Franke, Peter P. Pramstaller, Rainer Rettig, Inga Prokopenko, Jacqueline Witteman, Caroline Hayward, Paul M. Ridker, Murielle Bochud, Iris M. Heid, David S. Siscovick, Caroline S. Fox, W. Linda Kao, Carsten A. Böger

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

24 Scopus citations

Abstract

Many common genetic variants identified by genome-wide association studies for complex traitsmap to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research.

Original language	English (US)
Pages (from-to)	2105-2117
Number of pages	13
Journal	Journal of the American Society of Nephrology
Volume	24
Issue number	12
DOIs	https://doi.org/10.1681/ASN.2012100983
State	Published - 2013

ASJC Scopus subject areas

Nephrology

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10.1681/ASN.2012100983

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Parsa, A., Fuchsberger, C., Köttgen, A., O'Seaghdha, C. M., Pattaro, C., De Andrade, M., Chasman, D. I., Teumer, A., Endlich, K., Olden, M., Chen, M. H., Tin, A., Kim, Y. J., Taliun, D., Li, M., Feitosa, M., Gorski, M., Yang, Q., Hundertmark, C., ... Böger, C. A. (2013). Common variants in mendelian kidney disease genes and their association with renal function. Journal of the American Society of Nephrology, 24(12), 2105-2117. https://doi.org/10.1681/ASN.2012100983

Parsa, A, Fuchsberger, C, Köttgen, A, O'Seaghdha, CM, Pattaro, C, De Andrade, M, Chasman, DI, Teumer, A, Endlich, K, Olden, M, Chen, MH, Tin, A, Kim, YJ, Taliun, D, Li, M, Feitosa, M, Gorski, M, Yang, Q, Hundertmark, C, Foster, MC, Glazer, N, Isaacs, A, Rao, M, Smith, AV, O'Connell, JR, Struchalin, M, Tanaka, T, Li, G, Hwang, SJ, Atkinson, EJ, Lohman, K, Cornelis, MC, Johansson, A, Tönjes, A, Dehghan, A, Couraki, 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, Harris, TB, Launer, LJ, Aspelund, T, Eiriksdottir, G, Mitchell, BD, Boerwinkle, E, Schmidt, H, Hofer, E, Hu, F, Demirkan, A, Oostra, BA, Turner, ST, Ding, J, Andrews, JS, Freedman, BI, Giulianini, F, Koenig, W, Illig, T, Döring, A, Wichmann, HE, Zgaga, L, Zemunik, T, Boban, M, Minelli, C, Wheeler, HE, Igl, W, Zaboli, G, Wild, SH, Wright, AF, Campbell, H, Ellinghaus, D, Nöthlings, U, Jacobs, G, Biffar, R, Ernst, F, Homuth, G, Kroemer, HK, Nauck, M, Stracke, S, Völker, U, Völzke, H, Kovacs, P, Stumvoll, M, Mägi, R, Hofman, A, Uitterlinden, AG, Rivadeneira, F, Aulchenko, YS, Polasek, O, Hastie, N, Vitart, V, Helmer, C, Wang, JJ, Stengel, B, Ruggiero, D, Bergmann, S, Kähönen, M, Viikari, J, Nikopensius, T, Province, M, Colhoun, H, Doney, A, Robino, A, Krämer, BK, Portas, L, Ford, I, Buckley, BM, Adam, M, Thun, GA, Paulweber, B, Haun, M, Sala, C, Mitchell, P, Ciullo, M, 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, Van Duijn, CM, Borecki, I, Kardia, SLR, Liu, Y, Curhan, GC, Rudan, I, Gyllensten, U, Wilson, JF, Franke, A, Pramstaller, PP, Rettig, R, Prokopenko, I, Witteman, J, Hayward, C, Ridker, PM, Bochud, M, Heid, IM, Siscovick, DS, Fox, CS, Kao, WL & Böger, CA 2013, 'Common variants in mendelian kidney disease genes and their association with renal function', Journal of the American Society of Nephrology, vol. 24, no. 12, pp. 2105-2117. https://doi.org/10.1681/ASN.2012100983

@article{d3a523dbe38a43a48ead0491aa633b48,

title = "Common variants in mendelian kidney disease genes and their association with renal function",

abstract = "Many common genetic variants identified by genome-wide association studies for complex traitsmap to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research.",

author = "Afshin Parsa and Christian Fuchsberger and Anna K{\"o}ttgen and O'Seaghdha, {Conall M.} and Cristian Pattaro and {De Andrade}, Mariza and Chasman, {Daniel I.} and Alexander Teumer and Karlhans Endlich and Matthias Olden and Chen, {Ming Huei} and Adrienne Tin and Kim, {Young J.} and Daniel Taliun and Man Li and Mary Feitosa and Mathias Gorski and Qiong Yang and Claudia Hundertmark and Foster, {Meredith C.} and Nicole Glazer and Aaron Isaacs and Madhumathi Rao and Smith, {Albert V.} and O'Connell, {Jeffrey R.} and Maksim Struchalin and Toshiko Tanaka and Guo Li and Hwang, {Shih Jen} and Atkinson, {Elizabeth J.} and Kurt Lohman and Cornelis, {Marilyn C.} and Asa Johansson and Anke T{\"o}njes and Abbas Dehghan and Vincent Couraki 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 Harris, {Tamara B.} and Launer, {Lenore J.} and Thor Aspelund and Gudny Eiriksdottir and Mitchell, {Braxton D.} and Eric Boerwinkle and Helena Schmidt and Edith Hofer and Frank Hu and Ayse Demirkan and Oostra, {Ben A.} and Turner, {Stephen T.} and Jingzhong Ding and Andrews, {Jeanette S.} and Freedman, {Barry I.} and Franco Giulianini and Wolfgang Koenig and Thomas Illig and Angela D{\"o}ring and Wichmann, {H. Erich} and Lina Zgaga and Tatijana Zemunik and Mladen Boban and Cosetta Minelli and Wheeler, {Heather E.} and Wilmar Igl and Ghazal Zaboli and Wild, {Sarah H.} and Wright, {Alan F.} and Harry Campbell and David Ellinghaus and Ute N{\"o}thlings and Gunnar Jacobs and Reiner Biffar and Florian Ernst and Georg Homuth and Kroemer, {Heyo K.} and Matthias Nauck and Sylvia Stracke and Uwe V{\"o}lker and Henry V{\"o}lzke and Peter Kovacs and Michael Stumvoll and Reedik M{\"a}gi and Albert Hofman and Uitterlinden, {Andre G.} and Fernando Rivadeneira and Aulchenko, {Yurii S.} and Ozren Polasek and Nick Hastie and Veronique Vitart and Catherine Helmer and Wang, {Jie Jin} and B{\'e}n{\'e}dicte Stengel and Daniela Ruggiero and Sven Bergmann and Mika K{\"a}h{\"o}nen and Jorma Viikari and Tiit Nikopensius and Michael Province and Helen Colhoun and Alex Doney and Antonietta Robino and Kr{\"a}mer, {Bernhard K.} and Laura Portas and Ian Ford and Buckley, {Brendan M.} and Martin Adam and Thun, {Gian Andri} and Bernhard Paulweber and Margot Haun and Cinzia Sala and Paul Mitchell and Marina Ciullo and Peter Vollenweider and Olli Raitakari and Andres Metspalu and Colin Palmer and Paolo Gasparini and Mario Pirastu and Jukema, {J. Wouter} and Probst-Hensch, {Nicole M.} and Florian Kronenberg and Daniela Toniolo and Vilmundur Gudnason and Shuldiner, {Alan R.} and Josef Coresh and Reinhold Schmidt and Luigi Ferrucci and {Van Duijn}, {Cornelia M.} and Ingrid Borecki and Kardia, {Sharon L.R.} and Yongmei Liu and Curhan, {Gary C.} and Igor Rudan and Ulf Gyllensten and Wilson, {James F.} and Andre Franke and Pramstaller, {Peter P.} and Rainer Rettig and Inga Prokopenko and Jacqueline Witteman and Caroline Hayward and Ridker, {Paul M.} and Murielle Bochud and Heid, {Iris M.} and Siscovick, {David S.} and Fox, {Caroline S.} and Kao, {W. Linda} and B{\"o}ger, {Carsten A.}",

year = "2013",

doi = "10.1681/ASN.2012100983",

language = "English (US)",

volume = "24",

pages = "2105--2117",

journal = "Journal of the American Society of Nephrology : JASN",

issn = "1046-6673",

publisher = "American Society of Nephrology",

number = "12",

}

TY - JOUR

T1 - Common variants in mendelian kidney disease genes and their association with renal function

AU - Parsa, Afshin

AU - Fuchsberger, Christian

AU - Köttgen, Anna

AU - O'Seaghdha, Conall M.

AU - Pattaro, Cristian

AU - De Andrade, Mariza

AU - Chasman, Daniel I.

AU - Teumer, Alexander

AU - Endlich, Karlhans

AU - Olden, Matthias

AU - Chen, Ming Huei

AU - Tin, Adrienne

AU - Kim, Young J.

AU - Taliun, Daniel

AU - Li, Man

AU - Feitosa, Mary

AU - Gorski, Mathias

AU - Yang, Qiong

AU - Hundertmark, Claudia

AU - Foster, Meredith C.

AU - Glazer, Nicole

AU - Isaacs, Aaron

AU - Rao, Madhumathi

AU - Smith, Albert V.

AU - O'Connell, Jeffrey R.

AU - Struchalin, Maksim

AU - Tanaka, Toshiko

AU - Li, Guo

AU - Hwang, Shih Jen

AU - Atkinson, Elizabeth J.

AU - Lohman, Kurt

AU - Cornelis, Marilyn C.

AU - Johansson, Asa

AU - Tönjes, Anke

AU - Dehghan, Abbas

AU - Couraki, 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 - Harris, Tamara B.

AU - Launer, Lenore J.

AU - Aspelund, Thor

AU - Eiriksdottir, Gudny

AU - Mitchell, Braxton D.

AU - Boerwinkle, Eric

AU - Schmidt, Helena

AU - Hofer, Edith

AU - Hu, Frank

AU - Demirkan, Ayse

AU - Oostra, Ben A.

AU - Turner, Stephen T.

AU - Ding, Jingzhong

AU - Andrews, Jeanette S.

AU - Freedman, Barry I.

AU - Giulianini, Franco

AU - Koenig, Wolfgang

AU - Illig, Thomas

AU - Döring, Angela

AU - Wichmann, H. Erich

AU - Zgaga, Lina

AU - Zemunik, Tatijana

AU - Boban, Mladen

AU - Minelli, Cosetta

AU - Wheeler, Heather E.

AU - Igl, Wilmar

AU - Zaboli, Ghazal

AU - Wild, Sarah H.

AU - Wright, Alan F.

AU - Campbell, Harry

AU - Ellinghaus, David

AU - Nöthlings, Ute

AU - Jacobs, Gunnar

AU - Biffar, Reiner

AU - Ernst, Florian

AU - Homuth, Georg

AU - Kroemer, Heyo K.

AU - Nauck, Matthias

AU - Stracke, Sylvia

AU - Völker, Uwe

AU - Völzke, Henry

AU - Kovacs, Peter

AU - Stumvoll, Michael

AU - Mägi, Reedik

AU - Hofman, Albert

AU - Uitterlinden, Andre G.

AU - Rivadeneira, Fernando

AU - Aulchenko, Yurii S.

AU - Polasek, Ozren

AU - Hastie, Nick

AU - Vitart, Veronique

AU - Helmer, Catherine

AU - Wang, Jie Jin

AU - Stengel, Bénédicte

AU - Ruggiero, Daniela

AU - Bergmann, Sven

AU - Kähönen, Mika

AU - Viikari, Jorma

AU - Nikopensius, Tiit

AU - Province, Michael

AU - Colhoun, Helen

AU - Doney, Alex

AU - Robino, Antonietta

AU - Krämer, Bernhard K.

AU - Portas, Laura

AU - Ford, Ian

AU - Buckley, Brendan M.

AU - Adam, Martin

AU - Thun, Gian Andri

AU - Paulweber, Bernhard

AU - Haun, Margot

AU - Sala, Cinzia

AU - Mitchell, Paul

AU - Ciullo, Marina

AU - Vollenweider, Peter

AU - Raitakari, Olli

AU - Metspalu, Andres

AU - Palmer, Colin

AU - Gasparini, Paolo

AU - Pirastu, Mario

AU - Jukema, J. Wouter

AU - Probst-Hensch, Nicole M.

AU - Kronenberg, Florian

AU - Toniolo, Daniela

AU - Gudnason, Vilmundur

AU - Shuldiner, Alan R.

AU - Coresh, Josef

AU - Schmidt, Reinhold

AU - Ferrucci, Luigi

AU - Van Duijn, Cornelia M.

AU - Borecki, Ingrid

AU - Kardia, Sharon L.R.

AU - Liu, Yongmei

AU - Curhan, Gary C.

AU - Rudan, Igor

AU - Gyllensten, Ulf

AU - Wilson, James F.

AU - Franke, Andre

AU - Pramstaller, Peter P.

AU - Rettig, Rainer

AU - Prokopenko, Inga

AU - Witteman, Jacqueline

AU - Hayward, Caroline

AU - Ridker, Paul M.

AU - Bochud, Murielle

AU - Heid, Iris M.

AU - Siscovick, David S.

AU - Fox, Caroline S.

AU - Kao, W. Linda

AU - Böger, Carsten A.

PY - 2013

Y1 - 2013

N2 - Many common genetic variants identified by genome-wide association studies for complex traitsmap to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research.

AB - Many common genetic variants identified by genome-wide association studies for complex traitsmap to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research.

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UR - http://www.scopus.com/inward/citedby.url?scp=84889074946&partnerID=8YFLogxK

U2 - 10.1681/ASN.2012100983

DO - 10.1681/ASN.2012100983

M3 - Article

C2 - 24029420

AN - SCOPUS:84889074946

VL - 24

SP - 2105

EP - 2117

JO - Journal of the American Society of Nephrology : JASN

JF - Journal of the American Society of Nephrology : JASN

SN - 1046-6673

IS - 12

ER -

Common variants in mendelian kidney disease genes and their association with renal function

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