Common Variants in Mendelian Kidney Disease Genes and Their Association with Renal Function

A Parsa; C Fuchsberger; A Kottgen; CM O'Seaghdha; C Pattaro; M de Andrade; DI Chasman; A Teumer; K Endlich; M Olden; MH Chen; A Tin; YJ Kim; D Taliun; M Li; M Feitosa; M Gorski; Q Yang; C Hundertmark; MC Foster; N Glazer; Aaron Isaacs; M Rao; AV Smith; JR O'Connell; M Struchalin; T Tanaka; G (Guo) Li; SJ Hwang; EJ Atkinson; K Lohman; MC Cornelis; A Johansson; A Toenjes; Abbas Dehghan; V Couraki; EG Holliday; R Sorice; Z Kutalik; T Lehtimaeki; 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; E Hofer; F Hu; Ayse Demirkan; Ben Oostra; ST Turner; J Ding; JS Andrews; BI Freedman; F Giulianini; W Koenig; T Illig; A Doering; HE Wichmann; L Zgaga; T Zemunik; M Boban; C Minelli; HE Wheeler; W Igl; G Zaboli; SH Wild; AF Wright; H Campbell; D Ellinghaus; U Noethlings; G Jacobs; R Biffar; F Ernst; G Homuth; HK Kroemer; M Nauck; S Stracke; U Voelker; H Voelzke; P Kovacs; M Stumvoll; R Maegi; Bert Hofman; André Uitterlinden; Fernando Rivadeneira; YS Aulchenko; O Polasek; N Hastie; V Vitart; C Helmer; JJ Wang; B Stengel; D Ruggiero; S Bergmann; M Kaehoenen; J Viikari; T Nikopensius; M Province; H Colhoun; A Doney; A Robino; BK Kraemer; L Portas; I Ford; BM Buckley; M Adam; GA Thun; B Paulweber; M Haun; C Sala; P Mitchell; M Ciullo; 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; Cornelia Duijn; I Borecki; SLR Kardia; Y Liu; GC Curhan; I Rudan; U Gyllensten; JF Wilson; A Franke; PP Pramstaller; R Rettig; I Prokopenko; JCM Witteman; C Hayward; PM Ridker; M Bochud; IM Heid; DS Siscovick; CS Fox; WL Kao; CA Boeger

doi:10.1681/ASN.2012100983

Common Variants in Mendelian Kidney Disease Genes and Their Association with Renal Function

A Parsa, C Fuchsberger, A Kottgen, CM O'Seaghdha, C Pattaro, M de Andrade, DI Chasman, A Teumer, K Endlich, M Olden, MH Chen, A Tin, YJ Kim, D Taliun, M Li, M Feitosa, M Gorski, Q Yang, C Hundertmark, MC FosterN Glazer, Aaron Isaacs, M Rao, AV Smith, JR O'Connell, M Struchalin, T Tanaka, G (Guo) Li, SJ Hwang, EJ Atkinson, K Lohman, MC Cornelis, A Johansson, A Toenjes, Abbas Dehghan, V Couraki, EG Holliday, R Sorice, Z Kutalik, T Lehtimaeki, 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, E Hofer, F Hu, Ayse Demirkan, Ben Oostra, ST Turner, J Ding, JS Andrews, BI Freedman, F Giulianini, W Koenig, T Illig, A Doering, HE Wichmann, L Zgaga, T Zemunik, M Boban, C Minelli, HE Wheeler, W Igl, G Zaboli, SH Wild, AF Wright, H Campbell, D Ellinghaus, U Noethlings, G Jacobs, R Biffar, F Ernst, G Homuth, HK Kroemer, M Nauck, S Stracke, U Voelker, H Voelzke, P Kovacs, M Stumvoll, R Maegi, Bert Hofman, André Uitterlinden, Fernando Rivadeneira, YS Aulchenko, O Polasek, N Hastie, V Vitart, C Helmer, JJ Wang, B Stengel, D Ruggiero, S Bergmann, M Kaehoenen, J Viikari, T Nikopensius, M Province, H Colhoun, A Doney, A Robino, BK Kraemer, L Portas, I Ford, BM Buckley, M Adam, GA Thun, B Paulweber, M Haun, C Sala, P Mitchell, M Ciullo, 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, Cornelia Duijn, I Borecki, SLR Kardia, Y Liu, GC Curhan, I Rudan, U Gyllensten, JF Wilson, A Franke, PP Pramstaller, R Rettig, I Prokopenko, JCM Witteman, C Hayward, PM Ridker, M Bochud, IM Heid, DS Siscovick, CS Fox, WL Kao, CA Boeger

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

28 Citations (Scopus)

Abstract

Many common genetic variants identified by genome-wide association studies for complex traits map 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 2 meta-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
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
Publication status	Published - 2013

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10.1681/ASN.2012100983

http://hdl.handle.net/1765/68161

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Parsa, A., Fuchsberger, C., Kottgen, 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., ... Boeger, CA. (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

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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 traits map 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 2 meta-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 = "A Parsa and C Fuchsberger and A Kottgen and CM O'Seaghdha and C Pattaro and {de Andrade}, M and DI Chasman and A Teumer and K Endlich and M Olden and MH Chen and A Tin and YJ Kim and D Taliun and M Li and M Feitosa and M Gorski and Q Yang and C Hundertmark and MC Foster and N Glazer and Aaron Isaacs and M Rao and AV Smith and JR O'Connell and M Struchalin and T Tanaka and Li, {G (Guo)} and SJ Hwang and EJ Atkinson and K Lohman and MC Cornelis and A Johansson and A Toenjes and Abbas Dehghan and V Couraki and EG Holliday and R Sorice and Z Kutalik and T Lehtimaeki 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 E Hofer and F Hu and Ayse Demirkan and Ben Oostra and ST Turner and J Ding and JS Andrews and BI Freedman and F Giulianini and W Koenig and T Illig and A Doering and HE Wichmann and L Zgaga 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 Noethlings and G Jacobs and R Biffar and F Ernst and G Homuth and HK Kroemer and M Nauck and S Stracke and U Voelker and H Voelzke and P Kovacs and M Stumvoll and R Maegi 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 B Stengel and D Ruggiero and S Bergmann and M Kaehoenen and J Viikari and T Nikopensius and M Province and H Colhoun and A Doney and A Robino and BK Kraemer 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 P Mitchell and M Ciullo 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 Cornelia Duijn and I Borecki and SLR Kardia and Y 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 PM Ridker and M Bochud and IM Heid and DS Siscovick and CS Fox and WL Kao and CA Boeger",

year = "2013",

doi = "10.1681/ASN.2012100983",

language = "English",

volume = "24",

pages = "2105--2117",

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

issn = "1046-6673",

publisher = "American Society of Nephrology",

number = "12",

}

Parsa, A, Fuchsberger, C, Kottgen, 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, Toenjes, A, Dehghan, A, Couraki, V, Holliday, EG, Sorice, R, Kutalik, Z, Lehtimaeki, 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, B, Turner, ST, Ding, J, Andrews, JS, Freedman, BI, Giulianini, F, Koenig, W, Illig, T, Doering, 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, Noethlings, U, Jacobs, G, Biffar, R, Ernst, F, Homuth, G, Kroemer, HK, Nauck, M, Stracke, S, Voelker, U, Voelzke, H, Kovacs, P, Stumvoll, M, Maegi, R, Hofman, B , Uitterlinden, A , Rivadeneira, F, Aulchenko, YS, Polasek, O, Hastie, N, Vitart, V, Helmer, C, Wang, JJ, Stengel, B, Ruggiero, D, Bergmann, S, Kaehoenen, M, Viikari, J, Nikopensius, T, Province, M, Colhoun, H, Doney, A, Robino, A, Kraemer, 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, Duijn, C, Borecki, I, Kardia, SLR, Liu, Y, Curhan, GC, Rudan, I, Gyllensten, U, Wilson, JF, Franke, A, Pramstaller, PP, Rettig, R, Prokopenko, I, Witteman, JCM, Hayward, C, Ridker, PM, Bochud, M, Heid, IM, Siscovick, DS, Fox, CS, Kao, WL & Boeger, 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

TY - JOUR

T1 - Common Variants in Mendelian Kidney Disease Genes and Their Association with Renal Function

AU - Parsa, A

AU - Fuchsberger, C

AU - Kottgen, A

AU - O'Seaghdha, CM

AU - Pattaro, C

AU - de Andrade, M

AU - Chasman, DI

AU - Teumer, A

AU - Endlich, K

AU - Olden, M

AU - Chen, MH

AU - Tin, A

AU - Kim, YJ

AU - Taliun, D

AU - Li, M

AU - Feitosa, M

AU - Gorski, M

AU - Yang, Q

AU - Hundertmark, C

AU - Foster, MC

AU - Glazer, N

AU - Isaacs, Aaron

AU - Rao, M

AU - Smith, AV

AU - O'Connell, JR

AU - Struchalin, M

AU - Tanaka, T

AU - Li, G (Guo)

AU - Hwang, SJ

AU - Atkinson, EJ

AU - Lohman, K

AU - Cornelis, MC

AU - Johansson, A

AU - Toenjes, A

AU - Dehghan, Abbas

AU - Couraki, V

AU - Holliday, EG

AU - Sorice, R

AU - Kutalik, Z

AU - Lehtimaeki, 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 - Hofer, E

AU - Hu, F

AU - Demirkan, Ayse

AU - Oostra, Ben

AU - Turner, ST

AU - Ding, J

AU - Andrews, JS

AU - Freedman, BI

AU - Giulianini, F

AU - Koenig, W

AU - Illig, T

AU - Doering, A

AU - Wichmann, HE

AU - Zgaga, L

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 - Noethlings, U

AU - Jacobs, G

AU - Biffar, R

AU - Ernst, F

AU - Homuth, G

AU - Kroemer, HK

AU - Nauck, M

AU - Stracke, S

AU - Voelker, U

AU - Voelzke, H

AU - Kovacs, P

AU - Stumvoll, M

AU - Maegi, 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 - Stengel, B

AU - Ruggiero, D

AU - Bergmann, S

AU - Kaehoenen, M

AU - Viikari, J

AU - Nikopensius, T

AU - Province, M

AU - Colhoun, H

AU - Doney, A

AU - Robino, A

AU - Kraemer, 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 - Mitchell, P

AU - Ciullo, M

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 - Duijn, Cornelia

AU - Borecki, I

AU - Kardia, SLR

AU - Liu, Y

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, PM

AU - Bochud, M

AU - Heid, IM

AU - Siscovick, DS

AU - Fox, CS

AU - Kao, WL

AU - Boeger, CA

PY - 2013

Y1 - 2013

N2 - Many common genetic variants identified by genome-wide association studies for complex traits map 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 2 meta-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 traits map 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 2 meta-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.

U2 - 10.1681/ASN.2012100983

DO - 10.1681/ASN.2012100983

M3 - Article

SN - 1046-6673

VL - 24

SP - 2105

EP - 2117

JO - Journal of the American Society of Nephrology : JASN

JF - Journal of the American Society of Nephrology : JASN

IS - 12

ER -

Common Variants in Mendelian Kidney Disease Genes and Their Association with Renal Function

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