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 | |
| State | Published - 2013 |
ASJC Scopus subject areas
- Nephrology
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Common variants in mendelian kidney disease genes and their association with renal function. / Parsa, Afshin; Fuchsberger, Christian; Köttgen, Anna; O'Seaghdha, Conall M.; Pattaro, Cristian; De Andrade, Mariza; Chasman, Daniel I.; Teumer, Alexander; Endlich, Karlhans; Olden, Matthias; Chen, Ming Huei; Tin, Adrienne; Kim, Young J.; Taliun, Daniel; Li, Man; Feitosa, Mary; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C.; Glazer, Nicole; Isaacs, Aaron; Rao, Madhumathi; Smith, Albert V.; O'Connell, Jeffrey R.; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Hwang, Shih Jen; Atkinson, Elizabeth J.; Lohman, Kurt; Cornelis, Marilyn C.; Johansson, Asa; Tönjes, Anke; Dehghan, Abbas; Couraki, Vincent; Holliday, Elizabeth G.; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y.; Murgia, Federico; Trompet, Stella; Imboden, Medea; Kollerits, Barbara; Pistis, Giorgio; Harris, Tamara B.; Launer, Lenore J.; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D.; Boerwinkle, Eric; Schmidt, Helena; Hofer, Edith; Hu, Frank; Demirkan, Ayse; Oostra, Ben A.; Turner, Stephen T.; Ding, Jingzhong; Andrews, Jeanette S.; Freedman, Barry I.; Giulianini, Franco; Koenig, Wolfgang; Illig, Thomas; Döring, Angela; Wichmann, H. Erich; Zgaga, Lina; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E.; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H.; Wright, Alan F.; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K.; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G.; Rivadeneira, Fernando; Aulchenko, Yurii S.; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Stengel, Bénédicte; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Krämer, Bernhard K.; Portas, Laura; Ford, Ian; Buckley, Brendan M.; Adam, Martin; Thun, Gian Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Mitchell, Paul; Ciullo, Marina; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J. Wouter; Probst-Hensch, Nicole M.; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R.; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; Van Duijn, Cornelia M.; Borecki, Ingrid; Kardia, Sharon L.R.; Liu, Yongmei; Curhan, Gary C.; Rudan, Igor; Gyllensten, Ulf; Wilson, James F.; Franke, Andre; Pramstaller, Peter P.; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline; Hayward, Caroline; Ridker, Paul M.; Bochud, Murielle; Heid, Iris M.; Siscovick, David S.; Fox, Caroline S.; Kao, W. Linda; Böger, Carsten A.
In: Journal of the American Society of Nephrology, Vol. 24, No. 12, 2013, p. 2105-2117.Research output: Contribution to journal › Article › peer-review
}
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.
N1 - Copyright: Copyright 2013 Elsevier B.V., All rights reserved.
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.
UR - http://www.scopus.com/inward/record.url?scp=84889074946&partnerID=8YFLogxK
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 -