Author: "Ernst, F.D.J. (Florian)" - Searchworks@Jio Institute Digital Library Search Results

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1. Comparison of genotyping using pooled DNA samples (allelotyping) and individual genotyping using the affymetrix genome-wide human SNP array 6.0

Author: Teumer, A. (Alexander), Ernst, F.D.J. (Florian), Wiechert, M.A., Uhr, K. (Katharina), Nauck, M.A. (Matthias), Petersmann, A. (Astrid), Völzke, H. (Henry), Völker, U. (Uwe), Homuth, G. (Georg), Teumer, A. (Alexander), Ernst, F.D.J. (Florian), Wiechert, M.A., Uhr, K. (Katharina), Nauck, M.A. (Matthias), Petersmann, A. (Astrid), Völzke, H. (Henry), Völker, U. (Uwe), and Homuth, G. (Georg)
Abstract: Background: Genome-wide association studies (GWAS) using array-based genotyping technology are widely used to identify genetic loci associated with complex diseases or other phenotypes. The costs of GWAS projects based on individual genotyping are still comparatively high and increase with the size of study populations. Genotyping using pooled DNA samples, as also being referred as to allelotyping approach, offers an alternative at affordable costs. In the p
Published: 2013
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2. Meta-Analysis of Genome-Wide Association Studies Identifies Six New Loci for Serum Calcium Concentrations

Author: O'Seaghdha, C.M. (Conall), Wu, H. (Hongsheng), Yang, Q. (Qiong), Kapur, K. (Karen), Guessous, I. (Idris), Zuber, P. (Patrick), Köttgen, A. (Anna), Stoudmann, C. (Candice), Teumer, A. (Alexander), Kutalik, Z. (Zoltán), Mangino, M. (Massimo), Dehghan, A. (Abbas), Zhang, W. (Weihua), Eiriksdottir, G. (Gudny), Li, G. (Guo), Tanaka, T. (Toshiko), Portas, L. (Laura), Lopez, L.M. (Lorna), Hayward, C. (Caroline), Lohman, K. (Kurt), Matsuda, K. (Koichi), Padmanabhan, S. (Sandosh), Firsov, D. (Dmitri), Sorice, R., Ulivi, S. (Shelia), Brockhaus, A.C. (A. Catharina), Kleber, M.E. (Marcus), Mahajan, A. (Anubha), Ernst, F.D.J. (Florian), Gudnason, V. (Vilmundur), Launer, L.J. (Lenore), Mace, A. (Aurelien), Boerwinkle, E.A. (Eric), Arking, D.E. (Dan), Tanikawa, C. (Chizu), Nakamura, Y. (Yusuke), Brown, M.J. (Morris), Gaspoz, J.-M. (Jean-Michel), Theler, J.-M. (Jean-Marc), Siscovick, D.S. (David), Psaty, B.M. (Bruce), Bergmann, S.M. (Sven), Vollenweider, P. (Peter), Vitart, V. (Veronique), Wright, A.F. (Alan), Zemunik, T. (Tatijana), Boban, M. (Mladen), Kolcic, I. (Ivana), Navarro, P. (Pau), Brown, E.M. (Edward), Estrada Gil, K. (Karol), Ding, J. (Jingzhong), Harris, T.B. (Tamara), Bandinelli, S. (Stefania), Hernandez, D.G. (Dena), Singleton, A. (Andrew), Girotto, S., Ruggiero, D., Adamo, P. (Pio) d', Robino, A. (Antonietta), Meitinger, T. (Thomas), Meisinger, C. (Christa), Davies, G. (Gail), Starr, J.M. (John), Chambers, J.C. (John), Boehm, B.O. (Bernhard), Winkelmann, B., Huang, J. (Jian), Murgia, D. (Daniela), Wild, S.H. (Sarah), Campbell, H. (Harry), Morris, A.D. (Andrew), Franco, O.H. (Oscar), Hofman, A. (Albert), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Vol̈ker, U. (Uwe), Hannemann, M. (Mario), Biffar, R. (Reiner), Hoffmann, W. (Wolfgang), Shin, S.-Y., Lescuyer, P. (Pierre), Henry, H. (Hughes), Schurmann, C. (Claudia), Munroe, P. (Patricia), Gasparini, P. (Paolo), Pirastu, N. (Nicola), Ciullo, M., Gieger, C. (Christian), März, W. (Winfried), Lind, L. (Lars), Spector, T.D. (Timothy), Smith, A.V. (Davey), Rudan, I. (Igor), Wilson, J.F. (James), Polasek, O. (Ozren), Deary, I.J. (Ian), Pirastu, M. (Mario), Ferrucci, L. (Luigi), Liu, Y. (YongMei), Kestenbaum, B. (Bryan), Kooner, J.S. (Jaspal), Witteman, J.C.M. (Jacqueline), Nauck, M. (Matthias), Kao, W.H.L. (Wen), Wallaschofski, H. (Henri), Bonny, O. (Olivier), Fox, C. (Craig), Bochud, M. (Murielle), O'Seaghdha, C.M. (Conall), Wu, H. (Hongsheng), Yang, Q. (Qiong), Kapur, K. (Karen), Guessous, I. (Idris), Zuber, P. (Patrick), Köttgen, A. (Anna), Stoudmann, C. (Candice), Teumer, A. (Alexander), Kutalik, Z. (Zoltán), Mangino, M. (Massimo), Dehghan, A. (Abbas), Zhang, W. (Weihua), Eiriksdottir, G. (Gudny), Li, G. (Guo), Tanaka, T. (Toshiko), Portas, L. (Laura), Lopez, L.M. (Lorna), Hayward, C. (Caroline), Lohman, K. (Kurt), Matsuda, K. (Koichi), Padmanabhan, S. (Sandosh), Firsov, D. (Dmitri), Sorice, R., Ulivi, S. (Shelia), Brockhaus, A.C. (A. Catharina), Kleber, M.E. (Marcus), Mahajan, A. (Anubha), Ernst, F.D.J. (Florian), Gudnason, V. (Vilmundur), Launer, L.J. (Lenore), Mace, A. (Aurelien), Boerwinkle, E.A. (Eric), Arking, D.E. (Dan), Tanikawa, C. (Chizu), Nakamura, Y. (Yusuke), Brown, M.J. (Morris), Gaspoz, J.-M. (Jean-Michel), Theler, J.-M. (Jean-Marc), Siscovick, D.S. (David), Psaty, B.M. (Bruce), Bergmann, S.M. (Sven), Vollenweider, P. (Peter), Vitart, V. (Veronique), Wright, A.F. (Alan), Zemunik, T. (Tatijana), Boban, M. (Mladen), Kolcic, I. (Ivana), Navarro, P. (Pau), Brown, E.M. (Edward), Estrada Gil, K. (Karol), Ding, J. (Jingzhong), Harris, T.B. (Tamara), Bandinelli, S. (Stefania), Hernandez, D.G. (Dena), Singleton, A. (Andrew), Girotto, S., Ruggiero, D., Adamo, P. (Pio) d', Robino, A. (Antonietta), Meitinger, T. (Thomas), Meisinger, C. (Christa), Davies, G. (Gail), Starr, J.M. (John), Chambers, J.C. (John), Boehm, B.O. (Bernhard), Winkelmann, B., Huang, J. (Jian), Murgia, D. (Daniela), Wild, S.H. (Sarah), Campbell, H. (Harry), Morris, A.D. (Andrew), Franco, O.H. (Oscar), Hofman, A. (Albert), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Vol̈ker, U. (Uwe), Hannemann, M. (Mario), Biffar, R. (Reiner), Hoffmann, W. (Wolfgang), Shin, S.-Y., Lescuyer, P. (Pierre), Henry, H. (Hughes), Schurmann, C. (Claudia), Munroe, P. (Patricia), Gasparini, P. (Paolo), Pirastu, N. (Nicola), Ciullo, M., Gieger, C. (Christian), März, W. (Winfried), Lind, L. (Lars), Spector, T.D. (Timothy), Smith, A.V. (Davey), Rudan, I. (Igor), Wilson, J.F. (James), Polasek, O. (Ozren), Deary, I.J. (Ian), Pirastu, M. (Mario), Ferrucci, L. (Luigi), Liu, Y. (YongMei), Kestenbaum, B. (Bryan), Kooner, J.S. (Jaspal), Witteman, J.C.M. (Jacqueline), Nauck, M. (Matthias), Kao, W.H.L. (Wen), Wallaschofski, H. (Henri), Bonny, O. (Olivier), Fox, C. (Craig), and Bochud, M. (Murielle)
Abstract: Calcium is vital to the normal functioning of multiple organ systems and its serum concentration is tightly regulated. Apart from CASR, the genes associated with serum calcium are largely unknown. We conducted a genome-wide association meta-analysis of 39,400 individuals from 17 population-based cohorts and investigated the 14 most strongly associated loci in ≤21,679 additional individuals. Seven l
Published: 2013
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3. Common variants in mendelian kidney disease genes and their association with renal function

Author: Parsa, A. (Afshin), Fuchsberger, C. (Christian), Köttgen, A. (Anna), O'Seaghdha, C.M. (Conall), Pattaro, C. (Cristian), Andrade, M. (Mariza) de, Chasman, D.I. (Daniel), Teumer, A. (Alexander), Endlich, K. (Karlhans), Olden, M. (Matthias), Chen, M-H. (Ming-Huei), Tin, A. (Adrienne), Kim, Y-J. (Yong-Jin), Taliun, D. (Daniel), Li, M. (Man), Feitosa, M.F. (Mary Furlan), Gorski, M. (Mathias), Yang, Q. (Qiong), Hundertmark, C. (Claudia), Foster, M.C. (Michael), Glazer, N. (Nicole), Isaacs, A.J. (Aaron), Rao, M. (Madhumathi), Smith, A.V. (Davey), O´Connell, J.R., Struchalin, M.V. (Maksim), Tanaka, T. (Toshiko), Li, G. (Guo), Hwang, S.J., Atkinson, E.J. (Elizabeth), Lohman, K. (Kurt), Cornelis, M. (Marilyn), Johansson, A. (Åsa), Tönjes, A. (Anke), Dehghan, A. (Abbas), Couraki, V. (Vincent), Holliday, E.G. (Elizabeth), Sorice, R., Kutalik, Z. (Zoltán), Lehtimäki, T. (Terho), Esko, T. (Tõnu), Deshmukh, H. (Harshal), Ulivi, S. (Shelia), Chu, A.Y. (Audrey), Murgia, D. (Daniela), Trompet, S. (Stella), Imboden, M. (Medea), Kollerits, B. (Barbara), Pistis, G. (Giorgio), Harris, T.B. (Tamara), Launer, L.J. (Lenore), Aspelund, T. (Thor), Eiriksdottir, G. (Gudny), Mitchell, B.D. (Braxton), Boerwinkle, E.A. (Eric), Schmidt, H. (Helena), Hofer, E. (Edith), Hu, F.B. (Frank), Demirkan, A. (Ayşe), Oostra, B.A. (Ben), Turner, S.T. (Stephen), Ding, J. (Jingzhong), Andrews, J.S. (Jeanette), Freedman, B.I. (Barry), Giulianini, F. (Franco), Koenig, W. (Wolfgang), Illig, T. (Thomas), Döring, A. (Angela), Wichmann, H.E. (Heinz Erich), Zgaga, L. (Lina), Zemunik, T. (Tatijana), Boban, M. (Mladen), Minelli, C. (Cosetta), Wheeler, H.E. (Heather), Igl, W. (Wilmar), Zaboli, G. (Ghazal), Wild, S.H. (Sarah), Wright, A.F. (Alan), Campbell, H. (Harry), Ellinghaus, D. (David), Nöthlings, U. (Ute), Jacobs, G. (Gunnar), Biffar, R. (Reiner), Ernst, F.D.J. (Florian), Homuth, G. (Georg), Kroemer, H.K. (Heyo), Nauck, M. (Matthias), Stracke, S. (Sylvia), Vol̈ker, U. (Uwe), Völzke, H. (Henry), Kovacs, P. (Peter), Stumvoll, M. (Michael), Mägi, R. (Reedik), Hofman, A. (Albert), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Aulchenko, Y.S. (Yurii), Polasek, O. (Ozren), Hastie, N. (Nick), Vitart, V. (Veronique), Helmer, C. (Catherine), Wang, J.J. (Jie Jin), Stengel, B. (Bernd), Ruggiero, D., Bergmann, S.M. (Sven), Kähönen, M. (Mika), Viikari, J. (Jorma), Nikopensius, T. (Tiit), Province, M.A. (Mike), Colhoun, H.M. (H.), Doney, A.S.F. (Alex), Robino, A. (Antonietta), Krämer, B.K. (Bernhard), Portas, L. (Laura), Ford, I. (Ian), Buckley, B.M. (Brendan M.), Adam, M. (Martin), Thun, G.-A. (Gian-Andri), Paulweber, B. (Bernhard), Haun, M. (Margot), Sala, C. (Cinzia), Mitchell, P. (Paul), Ciullo, M., Vollenweider, P. (Peter), Raitakari, O. (Olli), Metspalu, A. (Andres), Palmer, C.N.A. (Colin), Gasparini, P. (Paolo), Pirastu, M. (Mario), Jukema, J.W. (Jan Wouter), Probst-Hensch, N.M. (Nicole M.), Kronenberg, F. (Florian), Toniolo, D. (Daniela), Gudnason, V. (Vilmundur), Shuldiner, A.R. (Alan), Coresh, J. (Josef), Schmidt, R. (Reinhold), Ferrucci, L. (Luigi), Duijn, C.M. (Cornelia) van, Borecki, I.B. (Ingrid), Kardia, S.L.R. (Sharon), Liu, Y. (YongMei), Curhan, G.C. (Gary), Rudan, I. (Igor), Gyllensten, U. (Ulf), Wilson, J.F. (James), Franke, A. (Andre), Pramstaller, P.P. (Peter Paul), Rettig, R. (Rainer), Prokopenko, I. (Inga), Witteman, J.C.M. (Jacqueline), Hayward, C. (Caroline), Ridker, P.M. (Paul), Bochud, M. (Murielle), Heid, I.M. (Iris), Siscovick, D.S. (David), Fox, C.S. (Caroline), Kao, W.H.L. (Wen), Böger, C.A. (Carsten), Parsa, A. (Afshin), Fuchsberger, C. (Christian), Köttgen, A. (Anna), O'Seaghdha, C.M. (Conall), Pattaro, C. (Cristian), Andrade, M. (Mariza) de, Chasman, D.I. (Daniel), Teumer, A. (Alexander), Endlich, K. (Karlhans), Olden, M. (Matthias), Chen, M-H. (Ming-Huei), Tin, A. (Adrienne), Kim, Y-J. (Yong-Jin), Taliun, D. (Daniel), Li, M. (Man), Feitosa, M.F. (Mary Furlan), Gorski, M. (Mathias), Yang, Q. (Qiong), Hundertmark, C. (Claudia), Foster, M.C. (Michael), Glazer, N. (Nicole), Isaacs, A.J. (Aaron), Rao, M. (Madhumathi), Smith, A.V. (Davey), O´Connell, J.R., Struchalin, M.V. (Maksim), Tanaka, T. (Toshiko), Li, G. (Guo), Hwang, S.J., Atkinson, E.J. (Elizabeth), Lohman, K. (Kurt), Cornelis, M. (Marilyn), Johansson, A. (Åsa), Tönjes, A. (Anke), Dehghan, A. (Abbas), Couraki, V. (Vincent), Holliday, E.G. (Elizabeth), Sorice, R., Kutalik, Z. (Zoltán), Lehtimäki, T. (Terho), Esko, T. (Tõnu), Deshmukh, H. (Harshal), Ulivi, S. (Shelia), Chu, A.Y. (Audrey), Murgia, D. (Daniela), Trompet, S. (Stella), Imboden, M. (Medea), Kollerits, B. (Barbara), Pistis, G. (Giorgio), Harris, T.B. (Tamara), Launer, L.J. (Lenore), Aspelund, T. (Thor), Eiriksdottir, G. (Gudny), Mitchell, B.D. (Braxton), Boerwinkle, E.A. (Eric), Schmidt, H. (Helena), Hofer, E. (Edith), Hu, F.B. (Frank), Demirkan, A. (Ayşe), Oostra, B.A. (Ben), Turner, S.T. (Stephen), Ding, J. (Jingzhong), Andrews, J.S. (Jeanette), Freedman, B.I. (Barry), Giulianini, F. (Franco), Koenig, W. (Wolfgang), Illig, T. (Thomas), Döring, A. (Angela), Wichmann, H.E. (Heinz Erich), Zgaga, L. (Lina), Zemunik, T. (Tatijana), Boban, M. (Mladen), Minelli, C. (Cosetta), Wheeler, H.E. (Heather), Igl, W. (Wilmar), Zaboli, G. (Ghazal), Wild, S.H. (Sarah), Wright, A.F. (Alan), Campbell, H. (Harry), Ellinghaus, D. (David), Nöthlings, U. (Ute), Jacobs, G. (Gunnar), Biffar, R. (Reiner), Ernst, F.D.J. (Florian), Homuth, G. (Georg), Kroemer, H.K. (Heyo), Nauck, M. (Matthias), Stracke, S. (Sylvia), Vol̈ker, U. (Uwe), Völzke, H. (Henry), Kovacs, P. (Peter), Stumvoll, M. (Michael), Mägi, R. (Reedik), Hofman, A. (Albert), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Aulchenko, Y.S. (Yurii), Polasek, O. (Ozren), Hastie, N. (Nick), Vitart, V. (Veronique), Helmer, C. (Catherine), Wang, J.J. (Jie Jin), Stengel, B. (Bernd), Ruggiero, D., Bergmann, S.M. (Sven), Kähönen, M. (Mika), Viikari, J. (Jorma), Nikopensius, T. (Tiit), Province, M.A. (Mike), Colhoun, H.M. (H.), Doney, A.S.F. (Alex), Robino, A. (Antonietta), Krämer, B.K. (Bernhard), Portas, L. (Laura), Ford, I. (Ian), Buckley, B.M. (Brendan M.), Adam, M. (Martin), Thun, G.-A. (Gian-Andri), Paulweber, B. (Bernhard), Haun, M. (Margot), Sala, C. (Cinzia), Mitchell, P. (Paul), Ciullo, M., Vollenweider, P. (Peter), Raitakari, O. (Olli), Metspalu, A. (Andres), Palmer, C.N.A. (Colin), Gasparini, P. (Paolo), Pirastu, M. (Mario), Jukema, J.W. (Jan Wouter), Probst-Hensch, N.M. (Nicole M.), Kronenberg, F. (Florian), Toniolo, D. (Daniela), Gudnason, V. (Vilmundur), Shuldiner, A.R. (Alan), Coresh, J. (Josef), Schmidt, R. (Reinhold), Ferrucci, L. (Luigi), Duijn, C.M. (Cornelia) van, Borecki, I.B. (Ingrid), Kardia, S.L.R. (Sharon), Liu, Y. (YongMei), Curhan, G.C. (Gary), Rudan, I. (Igor), Gyllensten, U. (Ulf), Wilson, J.F. (James), Franke, A. (Andre), Pramstaller, P.P. (Peter Paul), Rettig, R. (Rainer), Prokopenko, I. (Inga), Witteman, J.C.M. (Jacqueline), Hayward, C. (Caroline), Ridker, P.M. (Paul), Bochud, M. (Murielle), Heid, I.M. (Iris), Siscovick, D.S. (David), Fox, C.S. (Caroline), Kao, W.H.L. (Wen), and Böger, C.A. (Carsten)
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. Copyright
Published: 2013
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4. Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways

Author: Stolk, L. (Lisette), Broer, L. (Linda), Ernst, F.D.J. (Florian), Hottenga, J.J. (Jouke Jan), Kraft, P. (Peter), Chen, C. (Constance), Fauser, B.C.J.M. (Bart), Grobbee, D.E. (Diederick), Hofman, A. (Albert), Janssens, A.C.J.W. (Cécile), Johnson, A.D. (Andrew), Laven, J.S.E. (Joop), Martin, N.G. (Nicholas), Stolk, R.P. (Ronald), Nierop, P.W.M. (Peter) van, Vink, J.M. (Jacqueline), Zillikens, M.C. (Carola), Launer, L.J. (Lenore), Oostra, B.A. (Ben), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Murray, A. (Anna), Visser, J.A. (Jenny), Lunetta, K.L. (Kathryn), Stolk, L. (Lisette), Broer, L. (Linda), Ernst, F.D.J. (Florian), Hottenga, J.J. (Jouke Jan), Kraft, P. (Peter), Chen, C. (Constance), Fauser, B.C.J.M. (Bart), Grobbee, D.E. (Diederick), Hofman, A. (Albert), Janssens, A.C.J.W. (Cécile), Johnson, A.D. (Andrew), Laven, J.S.E. (Joop), Martin, N.G. (Nicholas), Stolk, R.P. (Ronald), Nierop, P.W.M. (Peter) van, Vink, J.M. (Jacqueline), Zillikens, M.C. (Carola), Launer, L.J. (Lenore), Oostra, B.A. (Ben), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Murray, A. (Anna), Visser, J.A. (Jenny), and Lunetta, K.L. (Kathryn)
Abstract: To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 - 10 g8). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-I °B signaling and mitochondrial dysfunction as biological processes related to timing of menopause.
Published: 2012
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5. Genome-wide association and functional follow-up reveals new loci for kidney function

Author: Pattaro, C. (Cristian), Köttgen, A. (Anna), Teumer, A. (Alexander), Böger, C.A. (Carsten), Fuchsberger, C. (Christian), Olden, M. (Matthias), Chen, M-H. (Ming-Huei), Li, M. (Man), Gao, X. (Xiaoyi), Gorski, M. (Mathias), Yang, Q. (Qiong Fang), O'Seaghdha, C.M. (Conall), Glazer, N.L. (Nicole), Isaacs, A.J. (Aaron), Liu, C.-T. (Ching-Ti), Smith, A.V. (Albert Vernon), O´Connell, J.R., Struchalin, M.V. (Maksim), Tanaka, T. (Toshiko), Johnson, A.D. (Andrew), Feitosa, M.F. (Mary Furlan), Hwang, S.J., Lohman, K. (Kurt), Cornelis, M. (Marilyn), Johansson, A. (Åsa), Tönjes, A. (Anke), Dehghan, A. (Abbas), Chouraki, V. (Vincent), Holliday, E.G. (Elizabeth), Sorice, R., Kutalik, Z. (Zoltán), Lehtimäki, T. (Terho), Esko, T. (Tõnu), Ulivi, S. (Shelia), Trompet, S. (Stella), Imboden, M. (Medea), Kollerits, B. (Barbara), Pistis, G. (Giorgio), Harris, T.B. (Tamara), Launer, L.J. (Lenore), Aspelund, T. (Thor), Eiriksdottir, G. (Gudny), Mitchell, B.D. (Braxton), Boerwinkle, E.A. (Eric), Schmidt, R. (Reinhold), Cavalieri, M. (Margherita), Hu, F.B. (Frank), Demirkan, A. (Ayşe), Oostra, B.A. (Ben), Andrade, M. (Mariza) de, Andrews, J.S. (Jeanette), Koenig, W. (Wolfgang), Illig, T. (Thomas), Döring, A. (Angela), Wichmann, H.E. (Erich), Kolcic, I. (Ivana), Zemunik, T. (Tatijana), Boban, M. (Mladen), Igl, W. (Wilmar), Zaboli, G. (Ghazal), Wild, S.H. (Sarah), Wright, A.F. (Alan), Campbell, H. (Harry), Biffar, R. (Reiner), Ernst, F.D.J. (Florian), Homuth, G. (Georg), Kroemer, H.K. (Heyo), Nauck, M. (Matthias), Kovacs, P. (Peter), Stumvoll, M. (Michael), Mägi, R. (Reedik), Hofman, A. (Albert), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Aulchenko, Y.S. (Yurii), Polasek, O. (Ozren), Hastie, N. (Nick), Vitart, V. (Veronique), Wang, J.J. (Jie Jin), Bergmann, S.M. (Sven), Kähönen, M. (Mika), Viikari, J. (Jorma), Province, M.A. (Mike), Ketkar, S. (Shamika), Doney, A.S.F. (Alex), Ford, I. (Ian), Buckley, B.M. (Brendan M.), Paulweber, B. (Bernhard), Haun, M. (Margot), Sala, C. (Cinzia), Ciullo, M., Vollenweider, P. (Peter), Raitakari, O. (Olli), Metspalu, A. (Andres), Palmer, C.N.A. (Colin), Gasparini, P. (Paolo), Jukema, J.W. (Jan Wouter), Kronenberg, F. (Florian), Toniolo, D. (Daniela), Gudnason, V. (Vilmundur), Shuldiner, A.R. (Alan), Coresh, J. (Josef), Ferrucci, L. (Luigi), Siscovick, D.S. (David), Tikka-Kleemola, P. (Päivi), Borecki, I.B. (Ingrid), Kardia, S.L.R. (Sharon), Curhan, G.C. (Gary), Rudan, I. (Igor), Gyllensten, U. (Ulf), Wilson, J.F. (James), Franke, A. (Andre), Pramstaller, P.P. (Peter Paul), Rettig, R. (Rainer), Prokopenko, I. (Inga), Witteman, J.C.M. (Jacqueline), Hayward, C. (Caroline), Ridker, P.M. (Paul), Parsa, A. (Afshin), Bochud, M. (Murielle), Heid, I.M. (Iris), Goessling, W. (Wolfram), Chasman, D.I. (Daniel), Kao, W.H.L. (Wen), Fox, C.S. (Caroline), Pattaro, C. (Cristian), Köttgen, A. (Anna), Teumer, A. (Alexander), Böger, C.A. (Carsten), Fuchsberger, C. (Christian), Olden, M. (Matthias), Chen, M-H. (Ming-Huei), Li, M. (Man), Gao, X. (Xiaoyi), Gorski, M. (Mathias), Yang, Q. (Qiong Fang), O'Seaghdha, C.M. (Conall), Glazer, N.L. (Nicole), Isaacs, A.J. (Aaron), Liu, C.-T. (Ching-Ti), Smith, A.V. (Albert Vernon), O´Connell, J.R., Struchalin, M.V. (Maksim), Tanaka, T. (Toshiko), Johnson, A.D. (Andrew), Feitosa, M.F. (Mary Furlan), Hwang, S.J., Lohman, K. (Kurt), Cornelis, M. (Marilyn), Johansson, A. (Åsa), Tönjes, A. (Anke), Dehghan, A. (Abbas), Chouraki, V. (Vincent), Holliday, E.G. (Elizabeth), Sorice, R., Kutalik, Z. (Zoltán), Lehtimäki, T. (Terho), Esko, T. (Tõnu), Ulivi, S. (Shelia), Trompet, S. (Stella), Imboden, M. (Medea), Kollerits, B. (Barbara), Pistis, G. (Giorgio), Harris, T.B. (Tamara), Launer, L.J. (Lenore), Aspelund, T. (Thor), Eiriksdottir, G. (Gudny), Mitchell, B.D. (Braxton), Boerwinkle, E.A. (Eric), Schmidt, R. (Reinhold), Cavalieri, M. (Margherita), Hu, F.B. (Frank), Demirkan, A. (Ayşe), Oostra, B.A. (Ben), Andrade, M. (Mariza) de, Andrews, J.S. (Jeanette), Koenig, W. (Wolfgang), Illig, T. (Thomas), Döring, A. (Angela), Wichmann, H.E. (Erich), Kolcic, I. (Ivana), Zemunik, T. (Tatijana), Boban, M. (Mladen), Igl, W. (Wilmar), Zaboli, G. (Ghazal), Wild, S.H. (Sarah), Wright, A.F. (Alan), Campbell, H. (Harry), Biffar, R. (Reiner), Ernst, F.D.J. (Florian), Homuth, G. (Georg), Kroemer, H.K. (Heyo), Nauck, M. (Matthias), Kovacs, P. (Peter), Stumvoll, M. (Michael), Mägi, R. (Reedik), Hofman, A. (Albert), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Aulchenko, Y.S. (Yurii), Polasek, O. (Ozren), Hastie, N. (Nick), Vitart, V. (Veronique), Wang, J.J. (Jie Jin), Bergmann, S.M. (Sven), Kähönen, M. (Mika), Viikari, J. (Jorma), Province, M.A. (Mike), Ketkar, S. (Shamika), Doney, A.S.F. (Alex), Ford, I. (Ian), Buckley, B.M. (Brendan M.), Paulweber, B. (Bernhard), Haun, M. (Margot), Sala, C. (Cinzia), Ciullo, M., Vollenweider, P. (Peter), Raitakari, O. (Olli), Metspalu, A. (Andres), Palmer, C.N.A. (Colin), Gasparini, P. (Paolo), Jukema, J.W. (Jan Wouter), Kronenberg, F. (Florian), Toniolo, D. (Daniela), Gudnason, V. (Vilmundur), Shuldiner, A.R. (Alan), Coresh, J. (Josef), Ferrucci, L. (Luigi), Siscovick, D.S. (David), Tikka-Kleemola, P. (Päivi), Borecki, I.B. (Ingrid), Kardia, S.L.R. (Sharon), Curhan, G.C. (Gary), Rudan, I. (Igor), Gyllensten, U. (Ulf), Wilson, J.F. (James), Franke, A. (Andre), Pramstaller, P.P. (Peter Paul), Rettig, R. (Rainer), Prokopenko, I. (Inga), Witteman, J.C.M. (Jacqueline), Hayward, C. (Caroline), Ridker, P.M. (Paul), Parsa, A. (Afshin), Bochud, M. (Murielle), Heid, I.M. (Iris), Goessling, W. (Wolfram), Chasman, D.I. (Daniel), Kao, W.H.L. (Wen), and Fox, C.S. (Caroline)
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.
Published: 2012
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6. Eight common genetic variants associated with serum dheas levels suggest a key role in ageing mechanisms

Author: Zhai, G. (Guangju), Teumer, A. (Alexander), Stolk, L. (Lisette), Perry, J.R.B. (John), Vandenput, L. (Liesbeth), Coviello, A.D. (Andrea), Koster, A. (Annemarie), Bell, J.T. (Jordana), Bhasin, S. (Shalender), Eriksson, J. (Joel), Ernst, F.D.J. (Florian), Ferrucci, L. (Luigi), Frayling, T.M. (Timothy), Glass, D. (Daniel), Grundberg, E. (Elin), Haring, R. (Robin), HedmanÅ, A.K., Hofman, A. (Albert), Kiel, D.P. (Douglas), Kroemer, H.K. (Heyo), Liu, Y. (YongMei), Lunetta, K.L. (Kathryn), Maggio, M. (Marcello), Lorentzon, M. (Mattias), Mangino, M. (Massimo), Melzer, D. (David), Miljkovic, I. (Iva), Nica, A. (Alexandra), Penninx, B.W.J.H. (Brenda), Vasan, R.S. (Ramachandran Srini), Rivadeneira Ramirez, F. (Fernando), Small, K.S. (Kerrin), Soranzo, N. (Nicole), Uitterlinden, A.G. (André), Völzke, H. (Henry), Wilson, S.G. (Scott), Xi, L. (Li), Zhuang, W.V., Jong, F.H. (Frank) de, Harris, T.B. (Tamara), Murabito, J. (Joanne), Ohlsson, C. (Claes), Murray, A. (Anna), Spector, T.D. (Timothy), Wallaschofski, H. (Henri), Zhai, G. (Guangju), Teumer, A. (Alexander), Stolk, L. (Lisette), Perry, J.R.B. (John), Vandenput, L. (Liesbeth), Coviello, A.D. (Andrea), Koster, A. (Annemarie), Bell, J.T. (Jordana), Bhasin, S. (Shalender), Eriksson, J. (Joel), Ernst, F.D.J. (Florian), Ferrucci, L. (Luigi), Frayling, T.M. (Timothy), Glass, D. (Daniel), Grundberg, E. (Elin), Haring, R. (Robin), HedmanÅ, A.K., Hofman, A. (Albert), Kiel, D.P. (Douglas), Kroemer, H.K. (Heyo), Liu, Y. (YongMei), Lunetta, K.L. (Kathryn), Maggio, M. (Marcello), Lorentzon, M. (Mattias), Mangino, M. (Massimo), Melzer, D. (David), Miljkovic, I. (Iva), Nica, A. (Alexandra), Penninx, B.W.J.H. (Brenda), Vasan, R.S. (Ramachandran Srini), Rivadeneira Ramirez, F. (Fernando), Small, K.S. (Kerrin), Soranzo, N. (Nicole), Uitterlinden, A.G. (André), Völzke, H. (Henry), Wilson, S.G. (Scott), Xi, L. (Li), Zhuang, W.V., Jong, F.H. (Frank) de, Harris, T.B. (Tamara), Murabito, J. (Joanne), Ohlsson, C. (Claes), Murray, A. (Anna), Spector, T.D. (Timothy), and Wallaschofski, H. (Henri)
Abstract: Dehydroepiandrosterone sulphate (DHEAS) is the most abundant circulating steroid secreted by adrenal glands-yet its function is unknown. Its serum concentration declines significantly with increasing age, which has led to speculation that a relative DHEAS deficiency may contribute to the development of common age-related diseases or diminished longevity. We conducted a meta-analysis of genome-wide association data with 14,846 individuals and identified eight independent common SNPs associated with serum DHEAS concentrations. Genes at or near the identified loci include ZKSCAN5 (rs11761528; p = 3.15×10-36), SULT2A1 (rs2637125; p = 2.61×10-19), ARPC1A (rs740160; p = 1.56×10-16), TRIM4 (rs17277546; p = 4.50×10-11), BMF (rs7181230; p = 5.44×10-11), HHEX (rs2497306; p = 4.64×10-9), BCL2L11 (rs6738028; p = 1.72×10-8), and CYP2C9 (rs2185570; p = 2.29×10-8). These genes are associated with type 2 diabetes, lymphoma, actin filament assembly, drug and xenobiotic metabolism, and zinc finger proteins. Several SNPs were associated with changes in gene expression levels, and the related genes are connected to biological pathways linking DHEAS with ageing. This study provides much needed insight into the function of DHEAS
Published: 2011
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7. Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque

Author: Bis, J.C. (Joshua), Kavousi, M. (Maryam), Franceschini, N. (Nora), Isaacs, A.J. (Aaron), Abecasis, G.R. (Gonçalo), Schminke, U. (Ulf), Post, W.S. (Wendy S.), Smith, A.V. (Albert Vernon), Cupples, L.A. (Adrienne), Markus, H.S. (Hugh S.), Schmidt, R. (Reinhold), Huffman, J.E. (Jennifer), Lehtimäki, T. (Terho), Baumert, J. (Jens), Münzel, T. (Thomas), Heckbert, S.R. (Susan), Dehghan, A. (Abbas), North, K.E. (Kari), Oostra, B.A. (Ben), Bevan, S. (Steve), Stoegerer, E.M. (Eva Maria), Hayward, C. (Caroline), Raitakari, O. (Olli), Meisinger, C. (Christa), Schillert, A. (Arne), Sanna, S. (Serena), Völzke, H. (Henry), Cheng, Y.C. (Yu Ching), Thorsson, B. (Bolli), Fox, C.S. (Caroline), Rice, K. (Kenneth), Rivadeneira Ramirez, F. (Fernando), Nambi, V. (Vijay), Halperin, E. (Eran), Petrovic, K. (Katja), Peltonen, L. (Leena Johanna), Wichmann, H.E. (Heinz Erich), Schnabel, R.B. (Renate), Dörr, M. (Marcus), Parsa, A. (Afshin), Aspelund, T. (Thor), Demissie, S. (Serkalem), Kathiresan, S. (Sekar), Reilly, M.P. (Muredach), Taylor, K.D. (Kent), Uitterlinden, A.G. (André), Couper, D.J. (David), Sitzer, M. (Matthias), Kähönen, M. (Mika), Illig, T. (Thomas), Wild, P.S. (Philipp), Orrù, M. (Marco), Lüdemann, J. (Jan), Shuldiner, A.R. (Alan), Eiriksdottir, G. (Gudny), White, C.C. (Charles), Rotter, J.I. (Jerome), Hofman, A. (Albert), Seissler, J. (Jochen), Zeller, T. (Tanja), Usala, G., Ernst, F.D.J. (Florian), Launer, L.J. (Lenore), D'Agostino, R.B. (Ralph), O'Leary, D.H. (Daniel H.), Ballantyne, C. (Christie), Thiery, J.P. (Joachim), Ziegler, A. (Andreas), Lakatta, E. (Edward), Chilukoti, R.K. (Ravi Kumar), Harris, T.B. (Tamara), Wolf, P.A. (Philip), Psaty, B.M. (Bruce), Polak, J.F. (Joseph F.), Rathmann, W. (Wolfgang), Uda, M. (Manuela), Boerwinkle, E.A. (Eric), Klopp, N. (Norman), Wilson, J.F. (James), Viikari, J. (Jorma), Koenig, W. (Wolfgang), Blankenberg, S. (Stefan), Newman, A.B. (Anne), Witteman, J.C.M. (Jacqueline), Li, X. (Xia), Heiss, G. (Gerardo), Duijn, C.M. (Cornelia) van, Scuteri, A. (Angelo), Homuth, G. (Georg), Mitchell, B.D. (Braxton), Gudnason, V. (Vilmundur), O'Donnell, C.J. (Christopher), Bis, J.C. (Joshua), Kavousi, M. (Maryam), Franceschini, N. (Nora), Isaacs, A.J. (Aaron), Abecasis, G.R. (Gonçalo), Schminke, U. (Ulf), Post, W.S. (Wendy S.), Smith, A.V. (Albert Vernon), Cupples, L.A. (Adrienne), Markus, H.S. (Hugh S.), Schmidt, R. (Reinhold), Huffman, J.E. (Jennifer), Lehtimäki, T. (Terho), Baumert, J. (Jens), Münzel, T. (Thomas), Heckbert, S.R. (Susan), Dehghan, A. (Abbas), North, K.E. (Kari), Oostra, B.A. (Ben), Bevan, S. (Steve), Stoegerer, E.M. (Eva Maria), Hayward, C. (Caroline), Raitakari, O. (Olli), Meisinger, C. (Christa), Schillert, A. (Arne), Sanna, S. (Serena), Völzke, H. (Henry), Cheng, Y.C. (Yu Ching), Thorsson, B. (Bolli), Fox, C.S. (Caroline), Rice, K. (Kenneth), Rivadeneira Ramirez, F. (Fernando), Nambi, V. (Vijay), Halperin, E. (Eran), Petrovic, K. (Katja), Peltonen, L. (Leena Johanna), Wichmann, H.E. (Heinz Erich), Schnabel, R.B. (Renate), Dörr, M. (Marcus), Parsa, A. (Afshin), Aspelund, T. (Thor), Demissie, S. (Serkalem), Kathiresan, S. (Sekar), Reilly, M.P. (Muredach), Taylor, K.D. (Kent), Uitterlinden, A.G. (André), Couper, D.J. (David), Sitzer, M. (Matthias), Kähönen, M. (Mika), Illig, T. (Thomas), Wild, P.S. (Philipp), Orrù, M. (Marco), Lüdemann, J. (Jan), Shuldiner, A.R. (Alan), Eiriksdottir, G. (Gudny), White, C.C. (Charles), Rotter, J.I. (Jerome), Hofman, A. (Albert), Seissler, J. (Jochen), Zeller, T. (Tanja), Usala, G., Ernst, F.D.J. (Florian), Launer, L.J. (Lenore), D'Agostino, R.B. (Ralph), O'Leary, D.H. (Daniel H.), Ballantyne, C. (Christie), Thiery, J.P. (Joachim), Ziegler, A. (Andreas), Lakatta, E. (Edward), Chilukoti, R.K. (Ravi Kumar), Harris, T.B. (Tamara), Wolf, P.A. (Philip), Psaty, B.M. (Bruce), Polak, J.F. (Joseph F.), Rathmann, W. (Wolfgang), Uda, M. (Manuela), Boerwinkle, E.A. (Eric), Klopp, N. (Norman), Wilson, J.F. (James), Viikari, J. (Jorma), Koenig, W. (Wolfgang), Blankenberg, S. (Stefan), Newman, A.B. (Anne), Witteman, J.C.M. (Jacqueline), Li, X. (Xia), Heiss, G. (Gerardo), Duijn, C.M. (Cornelia) van, Scuteri, A. (Angelo), Homuth, G. (Georg), Mitchell, B.D. (Braxton), Gudnason, V. (Vilmundur), and O'Donnell, C.J. (Christopher)
Abstract: Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 × 10 -8). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events.
Published: 2011
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8. Replication of the association of chromosomal region 9p21.3 with generalized aggressive periodontitis (gAgP) using an independent case-control cohort

Author: Ernst, F.D.J. (Florian), Uhr, K. (Katharina), Teumer, A. (Alexander), Fanghänel, J. (Jutta), Schulz, S. (Susanne), Noack, B. (Barbara), Gonzales, J. (Jose), Reichert, S. (Stefan), Eickholz, P. (Peter), Holtfreter, B. (Birte), Meisel, P. (Peter), Linden, G.J. (Gerard), Homuth, G. (Georg), Kocher, T. (Thomas), Ernst, F.D.J. (Florian), Uhr, K. (Katharina), Teumer, A. (Alexander), Fanghänel, J. (Jutta), Schulz, S. (Susanne), Noack, B. (Barbara), Gonzales, J. (Jose), Reichert, S. (Stefan), Eickholz, P. (Peter), Holtfreter, B. (Birte), Meisel, P. (Peter), Linden, G.J. (Gerard), Homuth, G. (Georg), and Kocher, T. (Thomas)
Abstract: Background: The human chromosomal region 9p21.3 has been shown to be strongly associated with Coronary Heart Disease (CHD) in several Genome-wide Association Studies (GWAS). Recently, this region has also been shown to be associated with Aggressive Periodontitis (AgP), strengthening the hypothesis that the established epidemiological association between periodontitis and CHD is caused by a shared genetic background, in addition to common environmental and behavioural risk factors. However, the size of the analyzed cohorts in this primary analysis was small compared to other association studies on complex diseases. Using our own AgP cohort, we attempted to confirm the described associations for the chromosomal region 9p21.3.Methods: We analyzed our cohort consisting of patients suffering from the most severe form of AgP, generalized AgP (gAgP) (n = 130) and appropriate periodontally healthy control individuals (n = 339) by genotyping four tagging SNPs (rs2891168, rs1333042, rs1333048 and rs496892), located in the chromosomal region 9p21.3, that have been associated with AgP.Results: The results confirmed significant associations between three of the four SNPs and gAgP. The combination of our results with those from the study which described this association for the first time in a meta-analysis of the four tagging SNPs produced clearly lower p-values compared with the results of each individual study. According to these results, the most plausible genetic model for the association of all four tested SNPs with gAgP seems to be the multiplicative one.Conclusion: We positively replicated the finding of an association between the chromosomal region 9p21.3 and gAgP. This result strengthens support for the hypothesis that shared susceptibility genes within this chromosomal locus might be involved in the pathogenesis of both CHD and gAgP.
Published: 2010
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9. Hundreds of variants clustered in genomic loci and biological pathways affect human height

Author: Allen, H.L., Estrada Gil, K. (Karol), Lettre, G. (Guillaume), Berndt, S.I. (Sonja), Rivadeneira Ramirez, F. (Fernando), Willer, C.J. (Cristen), Jackson, A.U. (Anne), Vedantam, S. (Sailaja), Raychaudhuri, S. (Soumya), Ferreira, T. (Teresa), Wood, A.R. (Andrew), Weyant, R.J. (Robert), Segrè, A.V. (Ayellet), Speliotes, E.K. (Elizabeth), Wheeler, E. (Eleanor), Soranzo, N. (Nicole), Park, J.H., Yang, J. (Joanna), Gudbjartsson, D.F. (Daniel), Heard-Costa, N.L. (Nancy), Randall, J.C. (Joshua), Qi, L. (Lu), Smith, A.V. (Albert Vernon), Mägi, R. (Reedik), Pastinen, T. (Tomi), Liang, L. (Liming), Heid, I.M. (Iris), Luan, J., Thorleifsson, G. (Gudmar), Winkler, T.W. (Thomas), Goddard, M.E. (Michael), Lo, K.S., Palmer, C. (Cameron), Workalemahu, T. (Tsegaselassie), Aulchenko, Y.S. (Yurii), Johansson, A. (Åsa), Zillikens, M.C. (Carola), Feitosa, M.F. (Mary Furlan), Esko, T. (Tõnu), Johnson, T. (Toby), Ketkar, S. (Shamika), Kraft, P. (Peter), Mangino, M. (Massimo), Prokopenko, I. (Inga), Absher, D. (Devin), Albrecht, E. (Eva), Ernst, F.D.J. (Florian), Glazer, N.L. (Nicole), Hayward, C. (Caroline), Hottenga, J.J. (Jouke Jan), Jacobs, K.B. (Kevin), Knowles, J.W. (Joshua), Kutalik, Z. (Zoltán), Monda, K.L. (Keri), Polasek, O. (Ozren), Preuss, M. (Michael), Rayner, N.W. (Nigel William), Robertson, N.R. (Neil), Steinthorsdottir, V. (Valgerdur), Tyrer, J.P. (Jonathan), Voight, B.F. (Benjamin), Wiklund, F. (Fredrik), Xu, J. (Jianfeng), Zhao, J.H. (Jing Hua), Nyholt, D.R. (Dale), Pellikka, N. (Niina), Perola, M. (Markus), Perry, J.R.B. (John), Surakka, I. (Ida), Tammesoo, M.L., Altmaier, E.L. (Elizabeth), Amin, N. (Najaf), Aspelund, T. (Thor), Bhangale, T. (Tushar), Boucher, G. (Gabrielle), Chasman, D.I. (Daniel), Chen, C. (Constance), Coin, L. (Lachlan), Cooper, M.N. (Matthew), Dixon, A.L. (Anna), Gibson, Q. (Quince), Grundberg, E. (Elin), Hao, K. (Ke), Junttila, M.J. (Juhani), Kaplan, R.C. (Robert), Kettunen, J. (Johannes), König, I.R. (Inke), Kwan, T. (Tony), Lawrence, R.W. (Robert), Levinson, D.F. (Douglas), Lorentzon, M. (Mattias), McKnight, B. (Barbara), Morris, A.D. (Andrew), Müller, M. (Martina), Ngwa, J.S., Purcell, S. (Shaun), Rafelt, S. (Suzanne), Salem, R.M. (Rany), Salvi, E. (Erika), Sanna, S. (Serena), Shi, J. (Jianxin), Sovio, U. (Ulla), Thompson, J.R. (John), Turchin, M.C. (Michael), Vandenput, L. (Liesbeth), Verlaan, D.J. (Dominique), Vitart, V. (Veronique), White, C.C. (Charles), Ziegler, A. (Andreas), Almgren, P. (Peter), Balmforth, A.J. (Anthony), Campbell, H. (Harry), Citterio, L. (Lorena), Grandi, A. (Alessandro) de, Dominiczak, A. (Anna), Duan, J. (Jubao), Elliott, P. (Paul), Elosua, R. (Roberto), Eriksson, J.G. (Johan), Freimer, N.B. (Nelson), Geus, E.J.C. (Eco) de, Glorioso, N. (Nicola), Haiqing, S. (Shen), Hartikainen, A.L., Havulinna, A.S. (Aki), Hicks, A.A. (Andrew), Hui, J. (Jennie), Igl, W. (Wilmar), Illig, T. (Thomas), Jula, A. (Antti), Kajantie, E. (Eero), Kilpeläinen, T.O. (Tuomas), Koiranen, M. (Markku), Kolcic, I. (Ivana), Koskinen, S. (Seppo), Kovacs, P. (Peter), Laitinen, J. (Jaana), Liu, J. (Jianjun), Lokki, M.L., Marusic, A. (Ana), Maschio, A., Meitinger, T. (Thomas), Mulas, A. (Antonella), Paré, G. (Guillaume), Parker, A.N. (Alex), Peden, J. (John), Petersmann, A. (Astrid), Pichler, I. (Irene), Pietilainen, K.H. (Kirsi Hannele), Pouta, A. (Anneli), Ridderstråle, M. (Martin), Rotter, J.I. (Jerome), Sambrook, J.G. (Jennifer), Sanders, A.R. (Alan), Schmidt, C.O. (Carsten Oliver), Sinisalo, J. (Juha), Smit, J.H. (Jan), Stringham, H.M. (Heather), Walters, G.B. (Bragi), Widen, E. (Elisabeth), Wild, S.H. (Sarah), Willemsen, G.A.H.M. (Gonneke), Zagato, L. (Laura), Zgaga, L. (Lina), Zitting, P. (Paavo), Alavere, H. (Helene), Farrall, M. (Martin), McArdle, W.L. (Wendy), Nelis, M. (Mari), Peters, M.J. (Marjolein), Ripatti, S. (Samuli), Meurs, J.B.J. (Joyce) van, Aben, K.K.H. (Katja), Beckmann, J.S. (Jacques), Beilby, J.P. (John), Bergman, R.N. (Richard), Bergmann, S.M. (Sven), Collins, F.S. (Francis), Cusi, D. (Daniele), Heijer, M. (Martin) den, Eiriksdottir, G. (Gudny), Gejman, P.V. (Pablo), Hall, A.S. (Alistair), Hamsten, A. (Anders), Huikuri, H.V. (Heikki), Iribarren, C. (Carlos), Kähönen, M. (Mika), Kaprio, J. (Jaakko), Kathiresan, S. (Sekar), Kiemeney, L.A.L.M. (Bart), Kocher, T. (Thomas), Launer, L.J. (Lenore), Lehtimäki, T. (Terho), Melander, O. (Olle), Mosley, T.H. (Thomas), Musk, A.W. (Arthur), Nieminen, M.S. (Markku), O'Donnell, C.J. (Christopher), Ohlsson, C. (Claes), Oostra, B.A. (Ben), Raitakari, O. (Olli), Ridker, P.M. (Paul), Rioux, J.D. (John), Rissanen, A. (Aila), Rivolta, C. (Carlo), Schunkert, H. (Heribert), Shuldiner, A.R. (Alan), Siscovick, D.S. (David), Stumvoll, M. (Michael), Tönjes, A. (Anke), Tuomilehto, J. (Jaakko), Ommen, G.J. (Gert) van, Viikari, J. (Jorma), Heath, A.C. (Andrew), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Province, M.A. (Mike), Kayser, M.H. (Manfred), Arnold, A.M. (Alice), Atwood, L.D. (Larry), Boerwinkle, E.A. (Eric), Chanock, S.J. (Stephen), Deloukas, P. (Panagiotis), Gieger, C. (Christian), Grönberg, H. (Henrik), Hattersley, A.T. (Andrew), Hengstenberg, C. (Christian), Hoffman, W. (Wolfgang), Lathrop, G.M. (Mark), Salomaa, V. (Veikko), Schreiber, S. (Stefan), Uda, M. (Manuela), Waterworth, D. (Dawn), Wright, A.F. (Alan), Assimes, T.L. (Themistocles), Barroso, I.E. (Inês), Hofman, A. (Albert), Mohlke, K.L. (Karen), Boomsma, D.I. (Dorret), Caulfield, M. (Mark), Cupples, L.A. (Adrienne), Fox, C.S. (Caroline), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Harris, T.B. (Tamara), Hayes, R.B. (Richard), Järvelin, M.R., Mooser, V. (Vincent), Munroe, P. (Patricia), Ouwehand, W.H. (Willem), Penninx, B.W.J.H. (Brenda), Pramstaller, P.P. (Peter Paul), Quertermous, T. (Thomas), Rudan, I. (Igor), Samani, N.J. (Nilesh), Spector, T.D. (Timothy), Völzke, H. (Henry), Watkins, H. (Hugh), Wilson, J.F. (James), Groop, L. (Leif), Haritunians, T. (Talin), Hu, F.B. (Frank), Metspalu, A. (Andres), North, K.E. (Kari), Schlessinger, D., Wareham, N.J. (Nick), Hunter, D.J. (David), O´Connell, J.R., Strachan, D.P. (David), Wichmann, H.E. (Heinz Erich), Borecki, I.B. (Ingrid), Duijn, C.M. (Cornelia) van, Schadt, E.E. (Eric), Thorsteinsdottir, U. (Unnur), Peltonen, L. (Leena Johanna), Uitterlinden, A.G. (André), Visscher, P.M. (Peter), Chatterjee, N. (Nilanjan), Erdmann, J. (Jeanette), Loos, R.J.F. (Ruth), Boehnke, M. (Michael), McCarthy, M.I. (Mark), Ingelsson, E. (Erik), Lindgren, C.M. (Cecilia), Abecasis, G.R. (Gonçalo), Stefansson, K. (Kari), Frayling, T.M. (Timothy), Hirschhorn, J.N. (Joel), Ardlie, K.G. (Kristin), Weedon, M.N. (Michael), Allen, H.L., Estrada Gil, K. (Karol), Lettre, G. (Guillaume), Berndt, S.I. (Sonja), Rivadeneira Ramirez, F. (Fernando), Willer, C.J. (Cristen), Jackson, A.U. (Anne), Vedantam, S. (Sailaja), Raychaudhuri, S. (Soumya), Ferreira, T. (Teresa), Wood, A.R. (Andrew), Weyant, R.J. (Robert), Segrè, A.V. (Ayellet), Speliotes, E.K. (Elizabeth), Wheeler, E. (Eleanor), Soranzo, N. (Nicole), Park, J.H., Yang, J. (Joanna), Gudbjartsson, D.F. (Daniel), Heard-Costa, N.L. (Nancy), Randall, J.C. (Joshua), Qi, L. (Lu), Smith, A.V. (Albert Vernon), Mägi, R. (Reedik), Pastinen, T. (Tomi), Liang, L. (Liming), Heid, I.M. (Iris), Luan, J., Thorleifsson, G. (Gudmar), Winkler, T.W. (Thomas), Goddard, M.E. (Michael), Lo, K.S., Palmer, C. (Cameron), Workalemahu, T. (Tsegaselassie), Aulchenko, Y.S. (Yurii), Johansson, A. (Åsa), Zillikens, M.C. (Carola), Feitosa, M.F. (Mary Furlan), Esko, T. (Tõnu), Johnson, T. (Toby), Ketkar, S. (Shamika), Kraft, P. (Peter), Mangino, M. (Massimo), Prokopenko, I. (Inga), Absher, D. (Devin), Albrecht, E. (Eva), Ernst, F.D.J. (Florian), Glazer, N.L. (Nicole), Hayward, C. (Caroline), Hottenga, J.J. (Jouke Jan), Jacobs, K.B. (Kevin), Knowles, J.W. (Joshua), Kutalik, Z. (Zoltán), Monda, K.L. (Keri), Polasek, O. (Ozren), Preuss, M. (Michael), Rayner, N.W. (Nigel William), Robertson, N.R. (Neil), Steinthorsdottir, V. (Valgerdur), Tyrer, J.P. (Jonathan), Voight, B.F. (Benjamin), Wiklund, F. (Fredrik), Xu, J. (Jianfeng), Zhao, J.H. (Jing Hua), Nyholt, D.R. (Dale), Pellikka, N. (Niina), Perola, M. (Markus), Perry, J.R.B. (John), Surakka, I. (Ida), Tammesoo, M.L., Altmaier, E.L. (Elizabeth), Amin, N. (Najaf), Aspelund, T. (Thor), Bhangale, T. (Tushar), Boucher, G. (Gabrielle), Chasman, D.I. (Daniel), Chen, C. (Constance), Coin, L. (Lachlan), Cooper, M.N. (Matthew), Dixon, A.L. (Anna), Gibson, Q. (Quince), Grundberg, E. (Elin), Hao, K. (Ke), Junttila, M.J. (Juhani), Kaplan, R.C. (Robert), Kettunen, J. (Johannes), König, I.R. (Inke), Kwan, T. (Tony), Lawrence, R.W. (Robert), Levinson, D.F. (Douglas), Lorentzon, M. (Mattias), McKnight, B. (Barbara), Morris, A.D. (Andrew), Müller, M. (Martina), Ngwa, J.S., Purcell, S. (Shaun), Rafelt, S. (Suzanne), Salem, R.M. (Rany), Salvi, E. (Erika), Sanna, S. (Serena), Shi, J. (Jianxin), Sovio, U. (Ulla), Thompson, J.R. (John), Turchin, M.C. (Michael), Vandenput, L. (Liesbeth), Verlaan, D.J. (Dominique), Vitart, V. (Veronique), White, C.C. (Charles), Ziegler, A. (Andreas), Almgren, P. (Peter), Balmforth, A.J. (Anthony), Campbell, H. (Harry), Citterio, L. (Lorena), Grandi, A. (Alessandro) de, Dominiczak, A. (Anna), Duan, J. (Jubao), Elliott, P. (Paul), Elosua, R. (Roberto), Eriksson, J.G. (Johan), Freimer, N.B. (Nelson), Geus, E.J.C. (Eco) de, Glorioso, N. (Nicola), Haiqing, S. (Shen), Hartikainen, A.L., Havulinna, A.S. (Aki), Hicks, A.A. (Andrew), Hui, J. (Jennie), Igl, W. (Wilmar), Illig, T. (Thomas), Jula, A. (Antti), Kajantie, E. (Eero), Kilpeläinen, T.O. (Tuomas), Koiranen, M. (Markku), Kolcic, I. (Ivana), Koskinen, S. (Seppo), Kovacs, P. (Peter), Laitinen, J. (Jaana), Liu, J. (Jianjun), Lokki, M.L., Marusic, A. (Ana), Maschio, A., Meitinger, T. (Thomas), Mulas, A. (Antonella), Paré, G. (Guillaume), Parker, A.N. (Alex), Peden, J. (John), Petersmann, A. (Astrid), Pichler, I. (Irene), Pietilainen, K.H. (Kirsi Hannele), Pouta, A. (Anneli), Ridderstråle, M. (Martin), Rotter, J.I. (Jerome), Sambrook, J.G. (Jennifer), Sanders, A.R. (Alan), Schmidt, C.O. (Carsten Oliver), Sinisalo, J. (Juha), Smit, J.H. (Jan), Stringham, H.M. (Heather), Walters, G.B. (Bragi), Widen, E. (Elisabeth), Wild, S.H. (Sarah), Willemsen, G.A.H.M. (Gonneke), Zagato, L. (Laura), Zgaga, L. (Lina), Zitting, P. (Paavo), Alavere, H. (Helene), Farrall, M. (Martin), McArdle, W.L. (Wendy), Nelis, M. (Mari), Peters, M.J. (Marjolein), Ripatti, S. (Samuli), Meurs, J.B.J. (Joyce) van, Aben, K.K.H. (Katja), Beckmann, J.S. (Jacques), Beilby, J.P. (John), Bergman, R.N. (Richard), Bergmann, S.M. (Sven), Collins, F.S. (Francis), Cusi, D. (Daniele), Heijer, M. (Martin) den, Eiriksdottir, G. (Gudny), Gejman, P.V. (Pablo), Hall, A.S. (Alistair), Hamsten, A. (Anders), Huikuri, H.V. (Heikki), Iribarren, C. (Carlos), Kähönen, M. (Mika), Kaprio, J. (Jaakko), Kathiresan, S. (Sekar), Kiemeney, L.A.L.M. (Bart), Kocher, T. (Thomas), Launer, L.J. (Lenore), Lehtimäki, T. (Terho), Melander, O. (Olle), Mosley, T.H. (Thomas), Musk, A.W. (Arthur), Nieminen, M.S. (Markku), O'Donnell, C.J. (Christopher), Ohlsson, C. (Claes), Oostra, B.A. (Ben), Raitakari, O. (Olli), Ridker, P.M. (Paul), Rioux, J.D. (John), Rissanen, A. (Aila), Rivolta, C. (Carlo), Schunkert, H. (Heribert), Shuldiner, A.R. (Alan), Siscovick, D.S. (David), Stumvoll, M. (Michael), Tönjes, A. (Anke), Tuomilehto, J. (Jaakko), Ommen, G.J. (Gert) van, Viikari, J. (Jorma), Heath, A.C. (Andrew), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Province, M.A. (Mike), Kayser, M.H. (Manfred), Arnold, A.M. (Alice), Atwood, L.D. (Larry), Boerwinkle, E.A. (Eric), Chanock, S.J. (Stephen), Deloukas, P. (Panagiotis), Gieger, C. (Christian), Grönberg, H. (Henrik), Hattersley, A.T. (Andrew), Hengstenberg, C. (Christian), Hoffman, W. (Wolfgang), Lathrop, G.M. (Mark), Salomaa, V. (Veikko), Schreiber, S. (Stefan), Uda, M. (Manuela), Waterworth, D. (Dawn), Wright, A.F. (Alan), Assimes, T.L. (Themistocles), Barroso, I.E. (Inês), Hofman, A. (Albert), Mohlke, K.L. (Karen), Boomsma, D.I. (Dorret), Caulfield, M. (Mark), Cupples, L.A. (Adrienne), Fox, C.S. (Caroline), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Harris, T.B. (Tamara), Hayes, R.B. (Richard), Järvelin, M.R., Mooser, V. (Vincent), Munroe, P. (Patricia), Ouwehand, W.H. (Willem), Penninx, B.W.J.H. (Brenda), Pramstaller, P.P. (Peter Paul), Quertermous, T. (Thomas), Rudan, I. (Igor), Samani, N.J. (Nilesh), Spector, T.D. (Timothy), Völzke, H. (Henry), Watkins, H. (Hugh), Wilson, J.F. (James), Groop, L. (Leif), Haritunians, T. (Talin), Hu, F.B. (Frank), Metspalu, A. (Andres), North, K.E. (Kari), Schlessinger, D., Wareham, N.J. (Nick), Hunter, D.J. (David), O´Connell, J.R., Strachan, D.P. (David), Wichmann, H.E. (Heinz Erich), Borecki, I.B. (Ingrid), Duijn, C.M. (Cornelia) van, Schadt, E.E. (Eric), Thorsteinsdottir, U. (Unnur), Peltonen, L. (Leena Johanna), Uitterlinden, A.G. (André), Visscher, P.M. (Peter), Chatterjee, N. (Nilanjan), Erdmann, J. (Jeanette), Loos, R.J.F. (Ruth), Boehnke, M. (Michael), McCarthy, M.I. (Mark), Ingelsson, E. (Erik), Lindgren, C.M. (Cecilia), Abecasis, G.R. (Gonçalo), Stefansson, K. (Kari), Frayling, T.M. (Timothy), Hirschhorn, J.N. (Joel), Ardlie, K.G. (Kristin), and Weedon, M.N. (Michael)
Abstract: Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits1, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait2,3. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways ( P=0.016) and that underlie skeletal growth defects ( P<0.001). Second, the likely causal gene is often located near the most str
Published: 2010
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10. Genome-wide association analysis identifies multiple loci related to resting heart rate

Author: Eijgelsheim, M. (Mark), Newton-Cheh, C. (Christopher), Sotoodehnia, N. (Nona), Bakker, P.I.W. (Paul) de, Müller, M. (Martina), Morrison, A.C. (Alanna), Smith, A.V. (Albert Vernon), Isaacs, A.J. (Aaron), Sanna, S. (Serena), Dörr, M. (Marcus), Navarro, P. (Pau), Fuchsberger, C. (Christian), Nolte, I.M. (Ilja), Geus, E.J.C. (Eco) de, Estrada Gil, K. (Karol), Hwang, S.J., Bis, J.C. (Joshua), Rückert, I.M., Alonso, A. (Alvaro), Launer, L.J. (Lenore), Hottenga, J.J. (Jouke Jan), Rivadeneira Ramirez, F. (Fernando), Noseworthy, P.A. (Peter), Rice, K. (Kenneth), Perz, S. (Siegfried), Arking, D.E. (Dan), Spector, T.D. (Timothy), Kors, J.A. (Jan), Aulchenko, Y.S. (Yurii), Tarasov, K.V. (Kirill), Homuth, G. (Georg), Wild, S.H. (Sarah), Marroni, F. (Fabio), Gieger, C. (Christian), Licht, C.M. (Carmilla), Prineas, R.J. (Ronald), Hofman, A. (Albert), Rotter, J.I. (Jerome), Hicks, A.A. (Andrew), Ernst, F.D.J. (Florian), Najjar, S.S. (Samer), Wright, A.F. (Alan), Peters, A. (Annette), Fox, E.R. (Ervin), Oostra, B.A. (Ben), Kroemer, H.K. (Heyo), Couper, D.J. (David), Völzke, H. (Henry), Campbell, H. (Harry), Meitinger, T. (Thomas), Uda, M. (Manuela), Witteman, J.C.M. (Jacqueline), Psaty, B.M. (Bruce), Wichmann, H.E. (Heinz Erich), Harris, T.B. (Tamara), Kääb, S. (Stefan), Siscovick, D.S. (David), Jamshidi, Y. (Yalda), Uitterlinden, A.G. (André), Folsom, A.R. (Aaron), Larson, M.G. (Martin), Wilson, J.F. (James), Penninx, B.W.J.H. (Brenda), Snieder, H. (Harold), Pramstaller, P.P. (Peter Paul), Tikka-Kleemola, P. (Päivi), Lakatta, E. (Edward), Felix, S.B. (Stephan), Gudnason, V. (Vilmundur), Pfeufer, A. (Arne), Heckbert, S.R. (Susan), Stricker, B.H.Ch. (Bruno), Boerwinkle, E.A. (Eric), O'Donnell, C.J. (Christopher), Eijgelsheim, M. (Mark), Newton-Cheh, C. (Christopher), Sotoodehnia, N. (Nona), Bakker, P.I.W. (Paul) de, Müller, M. (Martina), Morrison, A.C. (Alanna), Smith, A.V. (Albert Vernon), Isaacs, A.J. (Aaron), Sanna, S. (Serena), Dörr, M. (Marcus), Navarro, P. (Pau), Fuchsberger, C. (Christian), Nolte, I.M. (Ilja), Geus, E.J.C. (Eco) de, Estrada Gil, K. (Karol), Hwang, S.J., Bis, J.C. (Joshua), Rückert, I.M., Alonso, A. (Alvaro), Launer, L.J. (Lenore), Hottenga, J.J. (Jouke Jan), Rivadeneira Ramirez, F. (Fernando), Noseworthy, P.A. (Peter), Rice, K. (Kenneth), Perz, S. (Siegfried), Arking, D.E. (Dan), Spector, T.D. (Timothy), Kors, J.A. (Jan), Aulchenko, Y.S. (Yurii), Tarasov, K.V. (Kirill), Homuth, G. (Georg), Wild, S.H. (Sarah), Marroni, F. (Fabio), Gieger, C. (Christian), Licht, C.M. (Carmilla), Prineas, R.J. (Ronald), Hofman, A. (Albert), Rotter, J.I. (Jerome), Hicks, A.A. (Andrew), Ernst, F.D.J. (Florian), Najjar, S.S. (Samer), Wright, A.F. (Alan), Peters, A. (Annette), Fox, E.R. (Ervin), Oostra, B.A. (Ben), Kroemer, H.K. (Heyo), Couper, D.J. (David), Völzke, H. (Henry), Campbell, H. (Harry), Meitinger, T. (Thomas), Uda, M. (Manuela), Witteman, J.C.M. (Jacqueline), Psaty, B.M. (Bruce), Wichmann, H.E. (Heinz Erich), Harris, T.B. (Tamara), Kääb, S. (Stefan), Siscovick, D.S. (David), Jamshidi, Y. (Yalda), Uitterlinden, A.G. (André), Folsom, A.R. (Aaron), Larson, M.G. (Martin), Wilson, J.F. (James), Penninx, B.W.J.H. (Brenda), Snieder, H. (Harold), Pramstaller, P.P. (Peter Paul), Tikka-Kleemola, P. (Päivi), Lakatta, E. (Edward), Felix, S.B. (Stephan), Gudnason, V. (Vilmundur), Pfeufer, A. (Arne), Heckbert, S.R. (Susan), Stricker, B.H.Ch. (Bruno), Boerwinkle, E.A. (Eric), and O'Donnell, C.J. (Christopher)
Abstract: Higher resting heart rate is associated with increased cardiovascular disease and mortality risk. Though heritable factors play a substantial role in population variation, little is known about specific genetic determinants. This knowledge can impact clinical care by identifying novel factors that influence pathologic heart rate states, modulate heart rate through cardiac structure and function or by improving our understanding of the physiology of heart rate regulation. To identify common genetic variants associated with heart rate, we performed a meta-analysis of 15 genome-wide association studies (GWAS), including 38 991 subjects of European ancestry, estimating the association between age-, sex-and body mass-adjusted RR interval (inverse heart rate) and ~2.5 million markers. Results with P < 5 × 10-8were considered genome-wide significant. We constructed regression models with multiple markers to assess whether results at less stringent thresholds were likely to be truly associated with RR interval. We identified six novel associations with resting heart rate at six loci: 6q22 near GJA1; 14q12 near MYH7; 12p12 near SOX5, c12orf67, BCAT1, LRMP and CASC1; 6q22 near SLC35F1, PLN and c6orf204; 7q22 near SLC12A9 and UfSp1; and 11q12 near FADS1. Associations at 6q22 400 kb away from GJA1, at 14q12 MYH6 and at 1q32 near CD34 identified in previously published GWAS were confirmed. In aggregate, these variants explain ~0.7% of RR interval variance. A multivariant regre
Published: 2010
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11. Iron-responsive regulation of the Helicobacter pylori iron-cofactored superoxide dismutase SodB is mediated by Fur.

Author: Ernst, F.D.J. (Florian), Homuth, G. (Georg), Stoof, J. (Jeroen), Mader, U., Waidner, B. (Barbara), Kuipers, E.J. (Ernst), Kist, M. (Manfred), Kusters, J.G. (Johannes), Bereswill, S. (Stefan), Vliet, A.H.M. (Arnoud) van, Ernst, F.D.J. (Florian), Homuth, G. (Georg), Stoof, J. (Jeroen), Mader, U., Waidner, B. (Barbara), Kuipers, E.J. (Ernst), Kist, M. (Manfred), Kusters, J.G. (Johannes), Bereswill, S. (Stefan), and Vliet, A.H.M. (Arnoud) van
Abstract: Maintaining iron homeostasis is a necessity for all living organisms, as free iron augments the generation of reactive oxygen species like superoxide anions, at the risk of subsequent lethal cellular damage. The iron-responsive regulator Fur controls iron metabolism in many bacteria, including the important human pathogen Helicobacter pylori, and thus is directly or indirectly involved in regulation of oxidative stress defense. Here we demonstrate that Fur is a direct regulator of the H. pylori iron-cofactored superoxide dismutase SodB, which is essential for the defense against toxic superoxide radicals. Transcription of the sodB gene was iron induced in H. pylori wild-type strain 26695, resulting in expression of the SodB protein in iron-replete conditions but an absence of expression in iron-restricted conditions. Mutation of the fur gene resulted in constitutive, iron-independent expression of SodB. Recombinant H. pylori Fur protein bound with low affinity to the sodB promoter region, but addition of the iron substitute Mn2+ abolished binding. The operator sequence of the iron-free form of Fur, as identified by DNase I footprinting, was located directly upstream of the sodB gene at positions -5 to -47 from the transcription start site. The direct role of Fur in regulation of the H. pylori sodB gene contrasts with the small-RNA-mediated sodB regulation observed in Escherichia coli. In conclusion, H. pylori Fur is a versatile regulator involved in many pathways essential for gastric colonization, including superoxide stress defense.
Published: 2005
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12. The nickel-responsive regulator NikR controls activation and repression of gene transcription in Helicobacter pylori.

Author: Ernst, F.D.J. (Florian), Kuipers, E.J. (Ernst), Heijens, A. (Angela), Sarwari, R. (Roya), Stoof, J. (Jeroen), Penn, C.W. (Charles), Kusters, J.G. (Johannes), Vliet, A.H.M. (Arnoud) van, Ernst, F.D.J. (Florian), Kuipers, E.J. (Ernst), Heijens, A. (Angela), Sarwari, R. (Roya), Stoof, J. (Jeroen), Penn, C.W. (Charles), Kusters, J.G. (Johannes), and Vliet, A.H.M. (Arnoud) van
Abstract: The NikR protein is a nickel-dependent regulatory protein which is a member of the ribbon-helix-helix family of transcriptional regulators. The gastric pathogen Helicobacter pylori expresses a NikR ortholog, which was previously shown to mediate regulation of metal metabolism and urease expression, but the mechanism governing the diverse regulatory effects had not been described until now. In this study it is demonstrated that NikR can regulate H. pylori nickel metabolism by directly controlling transcriptional repression of NixA-mediated nickel uptake and transcriptional induction of urease expression. Mutation of the nickel uptake gene nixA in an H. pylori 26695 nikR mutant restored the ability to grow in Brucella media supplemented with 200 microM NiCl2 but did not restore nickel-dependent induction of urease expression. Nickel-dependent binding of NikR to the promoter of the nixA gene resulted in nickel-repressed transcription, whereas nickel-dependent binding of NikR to the promoter of the ureA gene resulted in nickel-induced transcription. Subsequent analysis of NikR binding to the nixA and ureA promoters showed that the regulatory effect was dependent on the location of the NikR-recognized binding sequence. NikR recognized the region from -13 to +21 of the nixA promoter, encompassing the +1 and -10 region, and this binding resulted in repression of nixA transcription. In contrast, NikR bound to the region from -56 to -91 upstream of the ureA promoter, resulting in induction of urease transcription. In conclusion, the NikR protein is able to function both as a repressor and as an activator of gene transcription, depending on the position of the binding site.
Published: 2005
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13. Transcriptional profiling of Helicobacter pylori Fur- and iron-regulated gene expression

Author: Ernst, F.D.J. (Florian), Bereswill, S. (Stefan), Waidner, B. (Barbara), Stoof, J. (Jeroen), Mader, U., Kusters, J.G. (Johannes), Kuipers, E.J. (Ernst), Kist, M. (Manfred), Vliet, A.H.M. (Arnoud) van, Homuth, G. (Georg), Ernst, F.D.J. (Florian), Bereswill, S. (Stefan), Waidner, B. (Barbara), Stoof, J. (Jeroen), Mader, U., Kusters, J.G. (Johannes), Kuipers, E.J. (Ernst), Kist, M. (Manfred), Vliet, A.H.M. (Arnoud) van, and Homuth, G. (Georg)
Abstract: Intracellular iron homeostasis is a necessity for almost all living organisms, since both iron restriction and iron overload can result in cell death. The ferric uptake regulator protein, Fur, controls iron homeostasis in most Gram-negative bacteria. In the human gastric pathogen Helicobacter pylori, Fur is thought to have acquired extra functions to compensate for the relative paucity of regulatory genes. To identify H. pylori genes regulated by iron and Fur, we used DNA array-based transcriptional profiling with RNA isolated from H. pylori 26695 wild-type and fur mutant cells grown in iron-restricted and iron-replete conditions. Sixteen genes encoding proteins involved in metal metabolism, nitrogen metabolism, motility, cell wall synthesis and cofactor synthesis displayed iron-dependent Fur-repressed expression. Conversely, 16 genes encoding proteins involved in iron storage, respiration, energy metabolism, chemotaxis, and oxygen scavenging displayed iron-induced Fur-dependent expression. Several Fur-regulated genes have been previously shown to be essential for acid resistance or gastric colonization in animal models, such as those encoding the hydrogenase and superoxide dismutase enzymes. Overall, there was a partial overlap between the sets of genes regulated by Fur and those previously identified as growth-phase, iron or acid regulated. Regulatory patterns were confirmed for five selected genes using Northern hybridization. In conclusion, H. pylori Fur is a versatile regulator involved in many pathways essential for gastric colonization. These findings further delineate the central role of Fur in regulating the unique capacity of H. pylori to colonize the human stomach.
Published: 2005

14. Transcriptional Regulation of the Nickel and Iron Metabolism in Helicobacter pylori

Author: Ernst, F.D.J. (Florian) and Ernst, F.D.J. (Florian)
Abstract: Up to 50 % of the world's population is infected with Helicobacter pylori. Colonization of the mucus layer of the human stomach by H. pylori, is lifelong unless treated with antibiotics (26). H. pylori, which is a neutralophilic bacterium, survives in the mucus layer of the human stomach with the help of the enzyme urease. Urease is an enzyme that converts urea into ammonium and carbon dioxide, thereby keeping the intracellular and periplasmic pH at neutral. It is estimated that up to 10% of the whole cell protein consists of this nickelcofactored enzyme (19). The nickel necessary to activate the urease is thought to come from foodsources, such as nuts, tea and cereals, which are rich in nickel (1). Metal ions like nickel or iron can be dangerous for bacteria, as they can react with oxygen in order to create reactive oxygen species that in turn can destroy macromolecules like nucleic acids, proteins and cell wall components (27). Therefore, the bacterial metal metabolism has to be tightly regulated. In H. pylori, regulatory proteins are scarce. Only two metal-regulatory proteins are known, the ferric uptake regulator Fur (4), and the nickel responsive regulator NikR (31). Fur is a regulatory protein that can sense and bind intracellular ferrous ions, and subsequently displays iron-dependent binding to conserved promoter sequences (Fur boxes) of its target genes (17). The classical regulation is repression of iron uptake genes in iron-replete conditions (15, 17, 33). Unlike all other Fur homologs known so far, H. pylori Fur can also bind to Fur-boxes in an iron free form (apo-Fur), as was shown for pfr (16) and sodB (Chapter 3). The second metal-dependent regulatory protein is NikR, the nickel responsive regulator, which belongs to the family of Ribbon-Helix-Helix regulatory proteins (9). NikR is directly involved in the regulation of acid resistance via urease and nickel-uptake (Chapter 4), and was previously demonstrated to mediate regulation of the ferric uptake r
Published: 2005

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1. Comparison of genotyping using pooled DNA samples (allelotyping) and individual genotyping using the affymetrix genome-wide human SNP array 6.0

2. Meta-Analysis of Genome-Wide Association Studies Identifies Six New Loci for Serum Calcium Concentrations

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

4. Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways

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

6. Eight common genetic variants associated with serum dheas levels suggest a key role in ageing mechanisms

7. Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque

8. Replication of the association of chromosomal region 9p21.3 with generalized aggressive periodontitis (gAgP) using an independent case-control cohort

9. Hundreds of variants clustered in genomic loci and biological pathways affect human height

10. Genome-wide association analysis identifies multiple loci related to resting heart rate

11. Iron-responsive regulation of the Helicobacter pylori iron-cofactored superoxide dismutase SodB is mediated by Fur.

12. The nickel-responsive regulator NikR controls activation and repression of gene transcription in Helicobacter pylori.

13. Transcriptional profiling of Helicobacter pylori Fur- and iron-regulated gene expression

14. Transcriptional Regulation of the Nickel and Iron Metabolism in Helicobacter pylori

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