100 results on '"Tikka-Kleemola P"'
Search Results
2. Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1
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Anttila, V., Stefansson, H., Kallela, M., Todt, U., Terwindt, G.M., Calafato, M.S., Nyholt, D.R., Dimas, A.S., Freilinger, T., Muller-Myhsok, B., Artto, V., Inouye, M., Alakurtti, K., Kaunisto, M.A., Hamalainen, E., Vries, B. de, Stam, A.H., Weller, C.M., Heinze, A., Heinze-Kuhn, K., Goebel, I., Borck, G., Gobel, H., Steinberg, S., Wolf, C., Bjornsson, A., Gudmundsson, G., Kirchmann, M., Hauge, A., Werge, T., Schoenen, J., Eriksson, J.G., Hagen, K., Stovner, L., Wichmann, E., Meitinger, T., Alexander, M., Moebus, S., Schreiber, S., Aulchenko, Y.S., Breteler, M.M.B., Uitterlinden, A.G., Hofman, A., Duijn, C.M. van, Tikka-Kleemola, P., Vepsalainen, Lucae, S., Tozzi, F., Muglia, P., Barrett, J., Kaprio, J., Farkkila, M., Peltonen, L., Stefansson, K., Zwart, J.A., Ferrari, M.D., Olesen, J., Daly, M., Wessman, M., Maagdenberg, A.M.J.M. van den, Dichgans, M., Kubisch, C., Dermitzakis, E.T., Frants, R.R., Palotie, A., and Int Headache Genetics Consortium
- Subjects
familial hemiplegic migraine lymphoblastoid cell-lines gene-expression episodic ataxia spreading depression confers risk mutation type-2 involvement mechanisms - Abstract
Migraine is a common episodic neurological disorder, typically presenting with recurrent attacks of severe headache and autonomic dysfunction. Apart from rare monogenic subtypes, no genetic or molecular markers for migraine have been convincingly established. We identified the minor allele of rs1835740 on chromosome 8q22.1 to be associated with migraine (P = 5.38 x 10(-9), odds ratio = 1.23, 95% CI 1.150-1.324) in a genome-wide association study of 2,731 migraine cases ascertained from three European headache clinics and 10,747 population-matched controls. The association was replicated in 3,202 cases and 40,062 controls for an overall meta-analysis P value of 1.69 x 10(-11) (odds ratio = 1.18, 95% CI 1.127-1.244). rs1835740 is located between MTDH (astrocyte elevated gene 1, also known as AEG-1) and PGCP (encoding plasma glutamate carboxypeptidase). In an expression quantitative trait study in lymphoblastoid cell lines, transcript levels of the MTDH were found to have a significant correlation to rs1835740 (P = 3.96 x 10(-5), permuted threshold for genome-wide significance 7.7 x 10(-5)). To our knowledge, our data establish rs1835740 as the first genetic risk factor for migraine.
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- 2010
3. Genome-wide association and functional follow-up reveals new loci for kidney function
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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.
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- 2012
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4. Genome-wide association studies of cerebral white matter lesion burden
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Fornage, M. (Myriam), Debette, S. (Stéphanie), Bis, J.C. (Joshua), Schmidt, R. (Reinhold), Ikram, M.A. (Arfan), Dufouil, C. (Carole), Sigurdsson, S. (Stefan), Lumley, T. (Thomas), DeStefano, A.L. (Anita), Fazekas, F. (Franz), Vrooman, H.A. (Henri), Shibata, D.K. (Dean), Maillard, P. (Pauline), Zijdenbos, A.P., Smith, A.V. (Albert Vernon), Gudnason, H. (Haukur), Boer, R. (Renske) de, Cushman, M. (Mary Ann), Mazoyer, B. (Bernard), Heiss, G. (Gerardo), Vernooij, M.W. (Meike), Enzinger, C. (Christian), Glazer, N.L. (Nicole), Beiser, A. (Alexa), Knopman, D.S. (David), Cavalieri, M. (Margherita), Niessen, W.J. (Wiro), Harris, T.B. (Tamara), Petrovic, K. (Katja), Lopez, O.L. (Oscar), Au, R. (Rhoda), Lambert, J.C. (Jean Charles), Hofman, A. (Albert), Gottesman, R.F. (Rebecca), Garcia, M. (Melissa), Heckbert, S.R. (Susan), Atwood, L.D. (Larry), Catellier, D.J. (Diane), Uitterlinden, A.G. (André), Yang, Q. (Qiong Fang), Aspelund, T. (Thor), Romero, J.R. (Jose Rafael), Rice, K. (Kenneth), Taylor, K.D. (Kent), Nalls, M.A. (Michael), Rotter, J.I. (Jerome), Sharrett, R. (Richey), Tikka-Kleemola, P. (Päivi), Amouyel, P. (Philippe), Wolf, P.A. (Philip), Lugt, A. (Aad) van der, Boerwinkle, E.A. (Eric), Psaty, B.M. (Bruce), Seshadri, S. (Sudha), Tzourio, C. (Christophe), Breteler, M.M.B. (Monique), Mosley, T.H. (Thomas), Longstreth Jr, W.T., DeCarli, C. (Charles), Launer, L.J. (Lenore), Fornage, M. (Myriam), Debette, S. (Stéphanie), Bis, J.C. (Joshua), Schmidt, R. (Reinhold), Ikram, M.A. (Arfan), Dufouil, C. (Carole), Sigurdsson, S. (Stefan), Lumley, T. (Thomas), DeStefano, A.L. (Anita), Fazekas, F. (Franz), Vrooman, H.A. (Henri), Shibata, D.K. (Dean), Maillard, P. (Pauline), Zijdenbos, A.P., Smith, A.V. (Albert Vernon), Gudnason, H. (Haukur), Boer, R. (Renske) de, Cushman, M. (Mary Ann), Mazoyer, B. (Bernard), Heiss, G. (Gerardo), Vernooij, M.W. (Meike), Enzinger, C. (Christian), Glazer, N.L. (Nicole), Beiser, A. (Alexa), Knopman, D.S. (David), Cavalieri, M. (Margherita), Niessen, W.J. (Wiro), Harris, T.B. (Tamara), Petrovic, K. (Katja), Lopez, O.L. (Oscar), Au, R. (Rhoda), Lambert, J.C. (Jean Charles), Hofman, A. (Albert), Gottesman, R.F. (Rebecca), Garcia, M. (Melissa), Heckbert, S.R. (Susan), Atwood, L.D. (Larry), Catellier, D.J. (Diane), Uitterlinden, A.G. (André), Yang, Q. (Qiong Fang), Aspelund, T. (Thor), Romero, J.R. (Jose Rafael), Rice, K. (Kenneth), Taylor, K.D. (Kent), Nalls, M.A. (Michael), Rotter, J.I. (Jerome), Sharrett, R. (Richey), Tikka-Kleemola, P. (Päivi), Amouyel, P. (Philippe), Wolf, P.A. (Philip), Lugt, A. (Aad) van der, Boerwinkle, E.A. (Eric), Psaty, B.M. (Bruce), Seshadri, S. (Sudha), Tzourio, C. (Christophe), Breteler, M.M.B. (Monique), Mosley, T.H. (Thomas), Longstreth Jr, W.T., DeCarli, C. (Charles), and Launer, L.J. (Lenore)
- Abstract
Objective: White matter hyperintensities (WMHs) detectable by magnetic resonance imaging are part of the spectrum of vascular injury associated with aging of the brain and are thought to reflect ischemic damage to the small deep cerebral vessels. WMHs are associated with an increased risk of cognitive and motor dysfunction, dementia, depression, and stroke. Despite a significant heritability, few genetic loci influencing WMH burden have been identified. Methods: We performed a meta-analysis of genome-wide association studies (GWASs) for WMH burden in 9,361 stroke-free individuals of European descent from 7 community-based cohorts. Significant findings were tested for replication in 3,024 individuals from 2 additional cohorts. Results: We identified 6 novel risk-associated single nucleotide polymorphisms (SNPs) in 1 locus on chromosome 17q25 encompassing 6 known genes including WBP2, TRIM65, TRIM47, MRPL38, FBF1, and ACOX1. The most significant association was for rs3744028 (pdiscovery= 4.0 × 10-9; preplication= 1.3 × 10-7; pcombined= 4.0 × 10-15). Other SNPs i
- Published
- 2011
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5. Strengthening the reporting of genetic risk prediction studies: the GRIPS statement.
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Janssens, A.C.J.W. (Cécile), Ioannidis, J.P.A. (John), Tikka-Kleemola, P. (Päivi), Little, J. (Julian), Khoury, M.J. (Muin Joseph), Janssens, A.C.J.W. (Cécile), Ioannidis, J.P.A. (John), Tikka-Kleemola, P. (Päivi), Little, J. (Julian), and Khoury, M.J. (Muin Joseph)
- Abstract
The number of known genetic markers of risk is increasing but the interpretation of their clinical effect is hampered by poor reporting of prediction studies. These guidelines from the GRIPS group aim to ensure transparent reporting of prediction studies
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- 2011
- Full Text
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6. Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure
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Wain, L.V. (Louise), Verwoert, G.C. (Germaine), O'Reilly, P.F. (Paul), Shi, G. (Gang), Johnson, T. (Toby), Bochud, M. (Murielle), Rice, K. (Kenneth), Henneman, P. (Peter), Smith, A.V. (Albert Vernon), Ehret, G.B. (Georg), Amin, N. (Najaf), Larson, M.G. (Martin), Mooser, V. (Vincent), Hadley, D. (David), Dörr, M. (Marcus), Bis, J.C. (Joshua), Aspelund, T. (Thor), Esko, T. (Tõnu), Janssens, A.C.J.W. (Cécile), Zhao, J.H. (Jing Hua), Heath, S.C. (Simon), Laan, M. (Maris), Fu, J. (Jingyuan), Pistis, G. (Giorgio), Luan, J., Lucas, G. (Gavin), Pirastu, N. (Nicola), Pichler, I. (Irene), Jackson, A.U. (Anne), Webster, R.J. (Rebecca J.), Zhang, F.F., Peden, J. (John), Schmidt, R. (Reinhold), Tanaka, T. (Toshiko), Campbell, H. (Harry), Igl, W. (Wilmar), Milaneschi, Y. (Yuri), Hottenga, J.J. (Jouke Jan), Vitart, V. (Veronique), Chasman, D.I. (Daniel), Trompet, S. (Stella), Bragg-Gresham, J.L. (Jennifer L.), Alizadeh, B.Z. (Behrooz), Chambers, J.C. (John), Guo, X. (Xiuqing), Lehtimäki, T. (Terho), Kuhnel, B. (Brigitte), Lopez, L.M., Polasek, O. (Ozren), Boban, M. (Mladen), Nelson, C.P. (Christopher P.), Morrison, A.C. (Alanna), Pihur, V. (Vasyl), Ganesh, S.K. (Santhi), Hofman, A. (Albert), Kundu, S. (Suman), Mattace Raso, F.U.S. (Francesco), Rivadeneira Ramirez, F. (Fernando), Sijbrands, E.J.G. (Eric), Uitterlinden, A.G. (André), Hwang, S.J., Vasan, R.S. (Ramachandran Srini), Wang, Y.A. (Ying), Bergmann, S.M. (Sven), Vollenweider, P. (Peter), Waeber, G. (Gérard), Laitinen, J. (Jaana), Pouta, A. (Anneli), Zitting, P. (Paavo), McArdle, W.L. (Wendy), Kroemer, H.K. (Heyo), Völker, U. (Uwe), Völzke, H. (Henry), Glazer, N.L. (Nicole), Taylor, K.D. (Kent), Harris, T.B. (Tamara), Alavere, H. (Helene), Haller, T. (Toomas), Keis, A. (Aime), Tammesoo, M.L., Aulchenko, Y.S. (Yurii), Khaw, K-T. (Kay-Tee), Galan, P. (Pilar), Hercberg, S. (Serge), Lathrop, G.M. (Mark), Eyheramendy, S. (Susana), Org, E. (Elin), Sõber, S. (Siim), Lu, X. (Xiaowen), Nolte, I.M. (Ilja), Penninx, B.W.J.H. (Brenda), Corre, T. (Tanguy), Masciullo, C. (Corrado), Sala, C. (Cinzia), Groop, L. (Leif), Voight, B.F. (Benjamin), Melander, O. (Olle), O'Donnell, C.J. (Christopher), Salomaa, V. (Veikko), Adamo, P. (Pio) d', Fabretto, A. (Antonella), Faletra, F. (Flavio), Ulivi, S. (Shelia), Del Greco, F. (Fabiola), Facheris, M.F. (Maurizio), Collins, F.S. (Francis), Bergman, R.N. (Richard), Beilby, J.P. (John), Hung, J. (Judy), Musk, A.W. (Arthur), Mangino, M. (Massimo), Shin, S.Y. (So Youn), Soranzo, N. (Nicole), Watkins, H. (Hugh), Goel, A. (Anuj), Hamsten, A. (Anders), Gider, P. (Pierre), Loitfelder, M. (Marisa), Zeginigg, M. (Marion), Hernandez, D.G. (Dena), Najjar, S.S. (Samer), Navarro, P. (Pau), Wild, S.H. (Sarah), Corsi, A.M. (Anna Maria), Singleton, A. (Andrew), Geus, E.J.C. (Eco) de, Willemsen, G.A.H.M. (Gonneke), Parker, A.N. (Alex), Rose, L.M. (Lynda), Buckley, B.M. (Brendan M.), Stott, D.J. (David. J.), Orrù, M. (Marco), Uda, M. (Manuela), Klauw, M.M. (Melanie) van der, Scott, J. (James), Chen, Y.D.I. (Yii-Der Ida), Burke, G.L. (Greg), Kähönen, M. (Mika), Viikari, J. (Jorma), Döring, A. (Angela), Meitinger, T. (Thomas), Davis, G.S., Starr, J.M. (John), Emilsson, V. (Valur), Plump, A.S. (Andrew), Lindeman, J.H. (Jan H.), Hoen, P.A.C. (Peter) 't, König, I.R. (Inke), Felix, J.F. (Janine), Clarke, R., Hopewell, J., Ongen, H. (Halit), Breteler, M.M.B. (Monique), Debette, S. (Stéphanie), DeStefano, A.L. (Anita), Fornage, M. (Myriam), Mitchell, G.F. (Gary), Holm, H. (Hilma), Stefansson, K. (Kari), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Samani, N.J. (Nilesh), Preuss, M. (Michael), Rudan, I. (Igor), Hayward, C. (Caroline), Deary, I.J. (Ian), Wichmann, H.E. (Heinz Erich), Raitakari, O. (Olli), Palmas, W. (Walter), Kooner, J.S. (Jaspal), Stolk, R.P. (Ronald), Jukema, J.W. (Jan Wouter), Wright, A.F. (Alan), Boomsma, D.I. (Dorret), Bandinelli, S. (Stefania), Gyllensten, U. (Ulf), Wilson, J.F. (James), Ferrucci, L. (Luigi), Farrall, M. (Martin), Spector, T.D. (Timothy), Palmer, L.J., Tuomilehto, J. (Jaakko), Pfeufer, A. (Arne), Gasparini, P. (Paolo), Siscovick, D.S. (David), Altshuler, D. (David), Loos, R.J.F. (Ruth), Toniolo, D. (Daniela), Snieder, H. (Harold), Gieger, C. (Christian), Meneton, P. (Pierre), Wareham, N.J. (Nick), Oostra, B.A. (Ben), Metspalu, A. (Andres), Launer, L.J. (Lenore), Rettig, R. (Rainer), Strachan, D.P. (David), Beckmann, J.S. (Jacques), Witteman, J.C.M. (Jacqueline), Willems van Dijk, J.A.P. (Ko), Boerwinkle, E.A. (Eric), Boehnke, M. (Michael), Ridker, P.M. (Paul), Järvelin, M.R., Chakravarti, A. (Aravinda), Erdmann, J. (Jeanette), Gudnason, V. (Vilmundur), Newton-Cheh, C. (Christopher), Levy, D. (Daniel), Arora, P. (Pankaj), Munroe, P. (Patricia), Psaty, B.M. (Bruce), Caulfield, M. (Mark), Li, X. (Xinzhong), Rao, D.C. (Dabeeru C.), Elliott, P. (Paul), Tikka-Kleemola, P. (Päivi), Abecasis, G.R. (Gonçalo), Barroso, I.E. (Inês), Wain, L.V. (Louise), Verwoert, G.C. (Germaine), O'Reilly, P.F. (Paul), Shi, G. (Gang), Johnson, T. (Toby), Bochud, M. (Murielle), Rice, K. (Kenneth), Henneman, P. (Peter), Smith, A.V. (Albert Vernon), Ehret, G.B. (Georg), Amin, N. (Najaf), Larson, M.G. (Martin), Mooser, V. (Vincent), Hadley, D. (David), Dörr, M. (Marcus), Bis, J.C. (Joshua), Aspelund, T. (Thor), Esko, T. (Tõnu), Janssens, A.C.J.W. (Cécile), Zhao, J.H. (Jing Hua), Heath, S.C. (Simon), Laan, M. (Maris), Fu, J. (Jingyuan), Pistis, G. (Giorgio), Luan, J., Lucas, G. (Gavin), Pirastu, N. (Nicola), Pichler, I. (Irene), Jackson, A.U. (Anne), Webster, R.J. (Rebecca J.), Zhang, F.F., Peden, J. (John), Schmidt, R. (Reinhold), Tanaka, T. (Toshiko), Campbell, H. (Harry), Igl, W. (Wilmar), Milaneschi, Y. (Yuri), Hottenga, J.J. (Jouke Jan), Vitart, V. (Veronique), Chasman, D.I. (Daniel), Trompet, S. (Stella), Bragg-Gresham, J.L. (Jennifer L.), Alizadeh, B.Z. (Behrooz), Chambers, J.C. (John), Guo, X. (Xiuqing), Lehtimäki, T. (Terho), Kuhnel, B. (Brigitte), Lopez, L.M., Polasek, O. (Ozren), Boban, M. (Mladen), Nelson, C.P. (Christopher P.), Morrison, A.C. (Alanna), Pihur, V. (Vasyl), Ganesh, S.K. (Santhi), Hofman, A. (Albert), Kundu, S. (Suman), Mattace Raso, F.U.S. (Francesco), Rivadeneira Ramirez, F. (Fernando), Sijbrands, E.J.G. (Eric), Uitterlinden, A.G. (André), Hwang, S.J., Vasan, R.S. (Ramachandran Srini), Wang, Y.A. (Ying), Bergmann, S.M. (Sven), Vollenweider, P. (Peter), Waeber, G. (Gérard), Laitinen, J. (Jaana), Pouta, A. (Anneli), Zitting, P. (Paavo), McArdle, W.L. (Wendy), Kroemer, H.K. (Heyo), Völker, U. (Uwe), Völzke, H. (Henry), Glazer, N.L. (Nicole), Taylor, K.D. (Kent), Harris, T.B. (Tamara), Alavere, H. (Helene), Haller, T. (Toomas), Keis, A. (Aime), Tammesoo, M.L., Aulchenko, Y.S. (Yurii), Khaw, K-T. (Kay-Tee), Galan, P. (Pilar), Hercberg, S. (Serge), Lathrop, G.M. (Mark), Eyheramendy, S. (Susana), Org, E. (Elin), Sõber, S. (Siim), Lu, X. (Xiaowen), Nolte, I.M. (Ilja), Penninx, B.W.J.H. (Brenda), Corre, T. (Tanguy), Masciullo, C. (Corrado), Sala, C. (Cinzia), Groop, L. (Leif), Voight, B.F. (Benjamin), Melander, O. (Olle), O'Donnell, C.J. (Christopher), Salomaa, V. (Veikko), Adamo, P. (Pio) d', Fabretto, A. (Antonella), Faletra, F. (Flavio), Ulivi, S. (Shelia), Del Greco, F. (Fabiola), Facheris, M.F. (Maurizio), Collins, F.S. (Francis), Bergman, R.N. (Richard), Beilby, J.P. (John), Hung, J. (Judy), Musk, A.W. (Arthur), Mangino, M. (Massimo), Shin, S.Y. (So Youn), Soranzo, N. (Nicole), Watkins, H. (Hugh), Goel, A. (Anuj), Hamsten, A. (Anders), Gider, P. (Pierre), Loitfelder, M. (Marisa), Zeginigg, M. (Marion), Hernandez, D.G. (Dena), Najjar, S.S. (Samer), Navarro, P. (Pau), Wild, S.H. (Sarah), Corsi, A.M. (Anna Maria), Singleton, A. (Andrew), Geus, E.J.C. (Eco) de, Willemsen, G.A.H.M. (Gonneke), Parker, A.N. (Alex), Rose, L.M. (Lynda), Buckley, B.M. (Brendan M.), Stott, D.J. (David. J.), Orrù, M. (Marco), Uda, M. (Manuela), Klauw, M.M. (Melanie) van der, Scott, J. (James), Chen, Y.D.I. (Yii-Der Ida), Burke, G.L. (Greg), Kähönen, M. (Mika), Viikari, J. (Jorma), Döring, A. (Angela), Meitinger, T. (Thomas), Davis, G.S., Starr, J.M. (John), Emilsson, V. (Valur), Plump, A.S. (Andrew), Lindeman, J.H. (Jan H.), Hoen, P.A.C. (Peter) 't, König, I.R. (Inke), Felix, J.F. (Janine), Clarke, R., Hopewell, J., Ongen, H. (Halit), Breteler, M.M.B. (Monique), Debette, S. (Stéphanie), DeStefano, A.L. (Anita), Fornage, M. (Myriam), Mitchell, G.F. (Gary), Holm, H. (Hilma), Stefansson, K. (Kari), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Samani, N.J. (Nilesh), Preuss, M. (Michael), Rudan, I. (Igor), Hayward, C. (Caroline), Deary, I.J. (Ian), Wichmann, H.E. (Heinz Erich), Raitakari, O. (Olli), Palmas, W. (Walter), Kooner, J.S. (Jaspal), Stolk, R.P. (Ronald), Jukema, J.W. (Jan Wouter), Wright, A.F. (Alan), Boomsma, D.I. (Dorret), Bandinelli, S. (Stefania), Gyllensten, U. (Ulf), Wilson, J.F. (James), Ferrucci, L. (Luigi), Farrall, M. (Martin), Spector, T.D. (Timothy), Palmer, L.J., Tuomilehto, J. (Jaakko), Pfeufer, A. (Arne), Gasparini, P. (Paolo), Siscovick, D.S. (David), Altshuler, D. (David), Loos, R.J.F. (Ruth), Toniolo, D. (Daniela), Snieder, H. (Harold), Gieger, C. (Christian), Meneton, P. (Pierre), Wareham, N.J. (Nick), Oostra, B.A. (Ben), Metspalu, A. (Andres), Launer, L.J. (Lenore), Rettig, R. (Rainer), Strachan, D.P. (David), Beckmann, J.S. (Jacques), Witteman, J.C.M. (Jacqueline), Willems van Dijk, J.A.P. (Ko), Boerwinkle, E.A. (Eric), Boehnke, M. (Michael), Ridker, P.M. (Paul), Järvelin, M.R., Chakravarti, A. (Aravinda), Erdmann, J. (Jeanette), Gudnason, V. (Vilmundur), Newton-Cheh, C. (Christopher), Levy, D. (Daniel), Arora, P. (Pankaj), Munroe, P. (Patricia), Psaty, B.M. (Bruce), Caulfield, M. (Mark), Li, X. (Xinzhong), Rao, D.C. (Dabeeru C.), Elliott, P. (Paul), Tikka-Kleemola, P. (Päivi), Abecasis, G.R. (Gonçalo), and Barroso, I.E. (Inês)
- Abstract
Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10 -8 to P = 2.3 × 10 -13) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP.
- Published
- 2011
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7. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk
- Author
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Ehret, G.B. (Georg), Munroe, P. (Patricia), Rice, K.M. (Kenneth), Bochud, M. (Murielle), Johnson, A.D. (Andrew), Chasman, D.I. (Daniel), Smith, A.V. (Albert Vernon), Tobin, M.D. (Martin), Verwoert, G.C. (Germaine), Hwang, S.J., Pihur, V. (Vasyl), Vollenweider, P. (Peter), O'Reilly, P.F. (Paul), Amin, N. (Najaf), Bragg-Gresham, J.L. (Jennifer L.), Teumer, A. (Alexander), Glazer, N.L. (Nicole), Launer, L.J. (Lenore), Zhao, J.H. (Jing Hua), Aulchenko, Y.S. (Yurii), Heath, S.C. (Simon), Sõber, S. (Siim), Parsa, A. (Afshin), Luan, J., Arora, P. (Pankaj), Dehghan, A. (Abbas), Zhang, F. (Feng), Lucas, G. (Gavin), Hicks, A.A. (Andrew), Jackson, A.U. (Anne), Peden, J. (John), Tanaka, T. (Toshiko), Wild, S.H. (Sarah), Rudan, I. (Igor), Igl, W. (Wilmar), Milaneschi, Y. (Yuri), Parker, A.N. (Alex), Fava, C. (Cristiano), Chambers, J.C. (John), Fox, E.R. (Ervin), Kumari, M. (Meena), Jin Go, M. (Min), Harst, P. (Pim) van der, Kao, W.-H.L. (Wen-Hong Linda), Sjögren, M. (Marketa), Vinay, D.G., Alexander, M. (Myriam), Tabara, Y. (Yasuharu), Shaw-Hawkins, S. (Sue), Whincup, P.H. (Peter), Liu, Y. (YongMei), Shi, G. (Gang), Kuusisto, J. (Johanna), Tayo, B. (Bamidele), Seielstad, M. (Mark), Sim, X. (Xueling), Hoang Nguyen, K.-D., Lehtimäki, T. (Terho), Matullo, G. (Giuseppe), Wu, Y. (Ying), Gaunt, T.R. (Tom), Onland-Moret, N.C. (Charlotte), Cooper, M.N. (Matthew), Platou, C. (Carl), Org, E. (Elin), Hardy, R. (Rebecca), Dahgam, S. (Santosh), Palmen, J. (Jutta), Vitart, V. (Veronique), Braund, P.S. (Peter), Kuznetsova, T. (Tatiana), Uiterwaal, C.S.P.M. (Cuno), Adeyemo, A. (Adebowale), Palmas, W. (Walter), Campbell, H. (Harry), Ludwig, B. (Barbara), Tomaszewski, M., Tzoulaki, I., Palmer, N.D. (Nicholette), Aspelund, T. (Thor), Garcia, M. (Melissa), Chang, Y.-P.C. (Yen-Pei), O´Connell, J.R., Steinle, N.I. (Nanette), Grobbee, D.E. (Diederick), Arking, D.E. (Dan), Kardia, S.L. (Sharon), Morrison, A.C. (Alanna), Hernandez, D.G. (Dena), Najjar, S.S. (Samer), McArdle, W.L. (Wendy), Hadley, D. (David), Brown, M.J. (Morris), Connell, J. (John), Hingorani, A. (Aroon), Day, I.N.M. (Ian), Lawlor, D.A. (Debbie), Beilby, J.P. (John), Lawrence, R.W. (Robert), Clarke, R., Hopewell, J., Ongen, H. (Halit), Dreisbach, A.W. (Albert), Li, Y. (Yali), Hunter Young, J., Bis, J.C. (Joshua), Kähönen, M. (Mika), Viikari, J. (Jorma), Lee, N.R. (Nanette), Chen, M-H. (Ming-Huei), Olden, M. (Matthias), Pattaro, C. (Cristian), Hoffman Bolton, J.A. (Judith), Köttgen, A. (Anna), Bergmann, S.M. (Sven), Mooser, V. (Vincent), Chaturvedi, N. (Nish), Frayling, T.M. (Timothy), Islam, M. (Muhammad), Jafar, T.H. (Tazeen), Kulkarni, S.R. (Smita), Bornstein, S.R. (Stefan), Gräßler, J. (Jürgen), Groop, L. (Leif), Voight, B.F. (Benjamin), Kettunen, J. (Johannes), Howard, P. (Philip), Taylor, A. (Andrew), Guarrera, S. (Simonetta), Ricceri, F. (Fulvio), Emilsson, V. (Valur), Plump, A.S. (Andrew), Khaw, K-T. (Kay-Tee), Weder, A.B. (Alan), Hunt, S.C. (Steven), Sun, Y.V. (Yan), Bergman, R.N. (Richard), Collins, F.S. (Francis), Bonnycastle, L.L. (Lori), Scott, L.J. (Laura), Stringham, H.M. (Heather), Peltonen, L. (Leena Johanna), Perola, M. (Markus), Vartiainen, E. (Erkki), Brand, S.-M., Staessen, J.A. (Jan), Wang, Y.A. (Ying), Burton, P.R. (Paul), Soler Artigas, M. (Maria), Dong, Y. (Yanbin), Snieder, H. (Harold), Zhu, H. (Haidong), Lohman, K. (Kurt), Rudock, M.E. (Megan), Heckbert, S.R. (Susan), Wiggins, K.L. (Kerri), Doumatey, A. (Ayo), Shriner, D. (Daniel), Veldre, G. (Gudrun), Viigimaa, M. (Margus), Kinra, S. (Sanjay), Prabhakaran, D. (Dorairaj), Tripathy, V. (Vikal), Langefeld, C.D. (Carl), Rosengren, A. (Annika), Thelle, D.S. (Dag), Corsi, A.M. (Anna Maria), Singleton, A. (Andrew), Forrester, T. (Terrence), Hilton, G. (Gina), McKenzie, C.A. (Colin), Salako, T. (Tunde), Iwai, N. (Naoharu), Kita, Y. (Yoshikuni), Ogihara, T. (Toshio), Ohkubo, T. (Takayoshi), Okamura, T. (Tomonori), Ueshima, H. (Hirotsugu), Umemura, S. (Satoshi), Eyheramendy, S. (Susana), Meitinger, T. (Thomas), Wichmann, H.E. (Heinz Erich), Shin Cho, Y. (Yoon), Kim, H.-L., Sehmi, J.S. (Joban), Hedblad, B. (Bo), Nilsson, P. (Peter), Davey-Smith, G. (George), Wong, A. (Andrew), Narisu, N. (Narisu), Stancáková, A. (Alena), Raffel, L.J. (Leslie), Yao, J. (Jie), Kathiresan, S. (Sekar), O'Donnell, C.J. (Christopher), Schwartz, S.M. (Stephen), Ikram, M.A. (Arfan), Longstreth Jr, W.T., Mosley, T.H. (Thomas), Seshadri, S. (Sudha), Shrine, N.R.G. (Nick), Wain, L.V. (Louise), Morken, M.A. (Mario), Swift, A.J. (Amy), Laitinen, J. (Jaana), Prokopenko, I. (Inga), Zitting, P. (Paavo), Humphries, S.E. (Steve), Danesh, J. (John), Rasheed, A. (Asif), Goel, A. (Anuj), Hamsten, A. (Anders), Watkins, H. (Hugh), Gilst, W.H. (Wiek) van, Janipalli, C.S. (Charles), Radha Mani, K., Yajnik, C. (Chittaranjan), Hofman, A. (Albert), Mattace Raso, F.U.S. (Francesco), Oostra, B.A. (Ben), Demirkan, A. (Ayşe), Isaacs, A.J. (Aaron), Rivadeneira Ramirez, F. (Fernando), Lakatta, E. (Edward), Orrù, M. (Marco), Scuteri, A. (Angelo), Ala-Korpela, M. (Mika), Kangas, A.J. (Antti), Lyytikäinen, L.-P. (Leo-Pekka), Soininen, P. (Pasi), Tukiainen, T. (Taru), Würtz, P. (Peter), Twee-Hee Ong, R. (Rick), Dörr, M. (Marcus), Kroemer, H.K. (Heyo), Völker, U. (Uwe), Völzke, H. (Henry), Galan, P. (Pilar), Hercberg, S. (Serge), Lathrop, G.M. (Mark), Zelenika, D. (Diana), Deloukas, P. (Panagiotis), Mangino, M. (Massimo), Spector, T.D. (Timothy), Zhai, G. (Guangju), Meschia, J.F. (James F.), Nalls, M.A. (Michael), Sharma, P. (Pankaj), Terzic, J. (Janos), Kranthi Kumar, M.V., Denniff, M. (Matthew), Zukowska-Szczechowska, E. (Ewa), Wagenknecht, L.E. (Lynne), Fowkes, F.G.R. (Gerald), Charchar, F.J. (Fadi), Schwarz, P.E.H. (Peter), Hayward, C. (Caroline), Guo, X. (Xiuqing), Rotimi, C. (Charles), Bots, M.L. (Michiel), Samani, N.J. (Nilesh), Polasek, O. (Ozren), Talmud, P.J. (Philippa), Nyberg, F. (Fredrik), Kuh, D. (Diana), Laan, M. (Maris), Hveem, K. (Kristian), Schouw, Y.T. (Yvonne) van der, Casas, J.P. (Juan), Mohlke, K.L. (Karen), Vineis, P. (Paolo), Raitakari, O. (Olli), Ganesh, S.K. (Santhi), Shyong Tai, E., Laakso, M. (Markku), Rao, D.C. (Dabeeru C.), Harris, T.B. (Tamara), Morris, R.W. (Richard), Dominiczak, A. (Anna), Kivimaki, M. (Mika), Marmot, M. (Michael), Miki, T. (Tetsuro), Saleheen, D., Chandak, G.R. (Giriraj), Coresh, J. (Josef), Navis, G. (Gerjan), Salomaa, V. (Veikko), Han, B.-G., Kooner, J.S. (Jaspal), Melander, O. (Olle), Ridker, P.M. (Paul), Bandinelli, S. (Stefania), Gyllensten, U. (Ulf), Wright, A.F. (Alan), Wilson, J.F. (James), Ferrucci, L. (Luigi), Farrall, M. (Martin), Tuomilehto, J. (Jaakko), Pramstaller, P.P. (Peter Paul), Elosua, R. (Roberto), Soranzo, N. (Nicole), Sijbrands, E.J.G. (Eric), Altshuler, D. (David), Loos, R.J.F. (Ruth), Shuldiner, A.R. (Alan), Gieger, C. (Christian), Meneton, P. (Pierre), Uitterlinden, A.G. (André), Wareham, N.J. (Nick), Gudnason, V. (Vilmundur), Rotter, J.I. (Jerome), Rettig, R. (Rainer), Uda, M. (Manuela), Strachan, D.P. (David), Witteman, J.C.M. (Jacqueline), Hartikainen, A.L., Beckmann, J.S. (Jacques), Boerwinkle, E.A. (Eric), Erdmann, J. (Jeanette), Vasan, R.S. (Ramachandran Srini), Boehnke, M. (Michael), Larson, M.G. (Martin), Järvelin, M.R., Psaty, B.M. (Bruce), Tikka-Kleemola, P. (Päivi), Newton-Cheh, C. (Christopher), Elliott, P. (Paul), Levy, D. (Daniel), Caulfield, M. (Mark), Abecasis, G.R. (Gonçalo), Adair, L.S. (Linda), Bakker, S.J.L. (Stephan), Barroso, I.E. (Inês), Ehret, G.B. (Georg), Munroe, P. (Patricia), Rice, K.M. (Kenneth), Bochud, M. (Murielle), Johnson, A.D. (Andrew), Chasman, D.I. (Daniel), Smith, A.V. (Albert Vernon), Tobin, M.D. (Martin), Verwoert, G.C. (Germaine), Hwang, S.J., Pihur, V. (Vasyl), Vollenweider, P. (Peter), O'Reilly, P.F. (Paul), Amin, N. (Najaf), Bragg-Gresham, J.L. (Jennifer L.), Teumer, A. (Alexander), Glazer, N.L. (Nicole), Launer, L.J. (Lenore), Zhao, J.H. (Jing Hua), Aulchenko, Y.S. (Yurii), Heath, S.C. (Simon), Sõber, S. (Siim), Parsa, A. (Afshin), Luan, J., Arora, P. (Pankaj), Dehghan, A. (Abbas), Zhang, F. (Feng), Lucas, G. (Gavin), Hicks, A.A. (Andrew), Jackson, A.U. (Anne), Peden, J. (John), Tanaka, T. (Toshiko), Wild, S.H. (Sarah), Rudan, I. (Igor), Igl, W. (Wilmar), Milaneschi, Y. (Yuri), Parker, A.N. (Alex), Fava, C. (Cristiano), Chambers, J.C. (John), Fox, E.R. (Ervin), Kumari, M. (Meena), Jin Go, M. (Min), Harst, P. (Pim) van der, Kao, W.-H.L. (Wen-Hong Linda), Sjögren, M. (Marketa), Vinay, D.G., Alexander, M. (Myriam), Tabara, Y. (Yasuharu), Shaw-Hawkins, S. (Sue), Whincup, P.H. (Peter), Liu, Y. (YongMei), Shi, G. (Gang), Kuusisto, J. (Johanna), Tayo, B. (Bamidele), Seielstad, M. (Mark), Sim, X. (Xueling), Hoang Nguyen, K.-D., Lehtimäki, T. (Terho), Matullo, G. (Giuseppe), Wu, Y. (Ying), Gaunt, T.R. (Tom), Onland-Moret, N.C. (Charlotte), Cooper, M.N. (Matthew), Platou, C. (Carl), Org, E. (Elin), Hardy, R. (Rebecca), Dahgam, S. (Santosh), Palmen, J. (Jutta), Vitart, V. (Veronique), Braund, P.S. (Peter), Kuznetsova, T. (Tatiana), Uiterwaal, C.S.P.M. (Cuno), Adeyemo, A. (Adebowale), Palmas, W. (Walter), Campbell, H. (Harry), Ludwig, B. (Barbara), Tomaszewski, M., Tzoulaki, I., Palmer, N.D. (Nicholette), Aspelund, T. (Thor), Garcia, M. (Melissa), Chang, Y.-P.C. (Yen-Pei), O´Connell, J.R., Steinle, N.I. (Nanette), Grobbee, D.E. (Diederick), Arking, D.E. (Dan), Kardia, S.L. (Sharon), Morrison, A.C. (Alanna), Hernandez, D.G. (Dena), Najjar, S.S. (Samer), McArdle, W.L. (Wendy), Hadley, D. (David), Brown, M.J. (Morris), Connell, J. (John), Hingorani, A. (Aroon), Day, I.N.M. (Ian), Lawlor, D.A. (Debbie), Beilby, J.P. (John), Lawrence, R.W. (Robert), Clarke, R., Hopewell, J., Ongen, H. (Halit), Dreisbach, A.W. (Albert), Li, Y. (Yali), Hunter Young, J., Bis, J.C. (Joshua), Kähönen, M. (Mika), Viikari, J. (Jorma), Lee, N.R. (Nanette), Chen, M-H. (Ming-Huei), Olden, M. (Matthias), Pattaro, C. (Cristian), Hoffman Bolton, J.A. (Judith), Köttgen, A. (Anna), Bergmann, S.M. (Sven), Mooser, V. (Vincent), Chaturvedi, N. (Nish), Frayling, T.M. (Timothy), Islam, M. (Muhammad), Jafar, T.H. (Tazeen), Kulkarni, S.R. (Smita), Bornstein, S.R. (Stefan), Gräßler, J. (Jürgen), Groop, L. (Leif), Voight, B.F. (Benjamin), Kettunen, J. (Johannes), Howard, P. (Philip), Taylor, A. (Andrew), Guarrera, S. (Simonetta), Ricceri, F. (Fulvio), Emilsson, V. (Valur), Plump, A.S. (Andrew), Khaw, K-T. (Kay-Tee), Weder, A.B. (Alan), Hunt, S.C. (Steven), Sun, Y.V. (Yan), Bergman, R.N. (Richard), Collins, F.S. (Francis), Bonnycastle, L.L. (Lori), Scott, L.J. (Laura), Stringham, H.M. (Heather), Peltonen, L. (Leena Johanna), Perola, M. (Markus), Vartiainen, E. (Erkki), Brand, S.-M., Staessen, J.A. (Jan), Wang, Y.A. (Ying), Burton, P.R. (Paul), Soler Artigas, M. (Maria), Dong, Y. (Yanbin), Snieder, H. (Harold), Zhu, H. (Haidong), Lohman, K. (Kurt), Rudock, M.E. (Megan), Heckbert, S.R. (Susan), Wiggins, K.L. (Kerri), Doumatey, A. (Ayo), Shriner, D. (Daniel), Veldre, G. (Gudrun), Viigimaa, M. (Margus), Kinra, S. (Sanjay), Prabhakaran, D. (Dorairaj), Tripathy, V. (Vikal), Langefeld, C.D. (Carl), Rosengren, A. (Annika), Thelle, D.S. (Dag), Corsi, A.M. (Anna Maria), Singleton, A. (Andrew), Forrester, T. (Terrence), Hilton, G. (Gina), McKenzie, C.A. (Colin), Salako, T. (Tunde), Iwai, N. (Naoharu), Kita, Y. (Yoshikuni), Ogihara, T. (Toshio), Ohkubo, T. (Takayoshi), Okamura, T. (Tomonori), Ueshima, H. (Hirotsugu), Umemura, S. (Satoshi), Eyheramendy, S. (Susana), Meitinger, T. (Thomas), Wichmann, H.E. (Heinz Erich), Shin Cho, Y. (Yoon), Kim, H.-L., Sehmi, J.S. (Joban), Hedblad, B. (Bo), Nilsson, P. (Peter), Davey-Smith, G. (George), Wong, A. (Andrew), Narisu, N. (Narisu), Stancáková, A. (Alena), Raffel, L.J. (Leslie), Yao, J. (Jie), Kathiresan, S. (Sekar), O'Donnell, C.J. (Christopher), Schwartz, S.M. (Stephen), Ikram, M.A. (Arfan), Longstreth Jr, W.T., Mosley, T.H. (Thomas), Seshadri, S. (Sudha), Shrine, N.R.G. (Nick), Wain, L.V. (Louise), Morken, M.A. (Mario), Swift, A.J. (Amy), Laitinen, J. (Jaana), Prokopenko, I. (Inga), Zitting, P. (Paavo), Humphries, S.E. (Steve), Danesh, J. (John), Rasheed, A. (Asif), Goel, A. (Anuj), Hamsten, A. (Anders), Watkins, H. (Hugh), Gilst, W.H. (Wiek) van, Janipalli, C.S. (Charles), Radha Mani, K., Yajnik, C. (Chittaranjan), Hofman, A. (Albert), Mattace Raso, F.U.S. (Francesco), Oostra, B.A. (Ben), Demirkan, A. (Ayşe), Isaacs, A.J. (Aaron), Rivadeneira Ramirez, F. (Fernando), Lakatta, E. (Edward), Orrù, M. (Marco), Scuteri, A. (Angelo), Ala-Korpela, M. (Mika), Kangas, A.J. (Antti), Lyytikäinen, L.-P. (Leo-Pekka), Soininen, P. (Pasi), Tukiainen, T. (Taru), Würtz, P. (Peter), Twee-Hee Ong, R. (Rick), Dörr, M. (Marcus), Kroemer, H.K. (Heyo), Völker, U. (Uwe), Völzke, H. (Henry), Galan, P. (Pilar), Hercberg, S. (Serge), Lathrop, G.M. (Mark), Zelenika, D. (Diana), Deloukas, P. (Panagiotis), Mangino, M. (Massimo), Spector, T.D. (Timothy), Zhai, G. (Guangju), Meschia, J.F. (James F.), Nalls, M.A. (Michael), Sharma, P. (Pankaj), Terzic, J. (Janos), Kranthi Kumar, M.V., Denniff, M. (Matthew), Zukowska-Szczechowska, E. (Ewa), Wagenknecht, L.E. (Lynne), Fowkes, F.G.R. (Gerald), Charchar, F.J. (Fadi), Schwarz, P.E.H. (Peter), Hayward, C. (Caroline), Guo, X. (Xiuqing), Rotimi, C. (Charles), Bots, M.L. (Michiel), Samani, N.J. (Nilesh), Polasek, O. (Ozren), Talmud, P.J. (Philippa), Nyberg, F. (Fredrik), Kuh, D. (Diana), Laan, M. (Maris), Hveem, K. (Kristian), Schouw, Y.T. (Yvonne) van der, Casas, J.P. (Juan), Mohlke, K.L. (Karen), Vineis, P. (Paolo), Raitakari, O. (Olli), Ganesh, S.K. (Santhi), Shyong Tai, E., Laakso, M. (Markku), Rao, D.C. (Dabeeru C.), Harris, T.B. (Tamara), Morris, R.W. (Richard), Dominiczak, A. (Anna), Kivimaki, M. (Mika), Marmot, M. (Michael), Miki, T. (Tetsuro), Saleheen, D., Chandak, G.R. (Giriraj), Coresh, J. (Josef), Navis, G. (Gerjan), Salomaa, V. (Veikko), Han, B.-G., Kooner, J.S. (Jaspal), Melander, O. (Olle), Ridker, P.M. (Paul), Bandinelli, S. (Stefania), Gyllensten, U. (Ulf), Wright, A.F. (Alan), Wilson, J.F. (James), Ferrucci, L. (Luigi), Farrall, M. (Martin), Tuomilehto, J. (Jaakko), Pramstaller, P.P. (Peter Paul), Elosua, R. (Roberto), Soranzo, N. (Nicole), Sijbrands, E.J.G. (Eric), Altshuler, D. (David), Loos, R.J.F. (Ruth), Shuldiner, A.R. (Alan), Gieger, C. (Christian), Meneton, P. (Pierre), Uitterlinden, A.G. (André), Wareham, N.J. (Nick), Gudnason, V. (Vilmundur), Rotter, J.I. (Jerome), Rettig, R. (Rainer), Uda, M. (Manuela), Strachan, D.P. (David), Witteman, J.C.M. (Jacqueline), Hartikainen, A.L., Beckmann, J.S. (Jacques), Boerwinkle, E.A. (Eric), Erdmann, J. (Jeanette), Vasan, R.S. (Ramachandran Srini), Boehnke, M. (Michael), Larson, M.G. (Martin), Järvelin, M.R., Psaty, B.M. (Bruce), Tikka-Kleemola, P. (Päivi), Newton-Cheh, C. (Christopher), Elliott, P. (Paul), Levy, D. (Daniel), Caulfield, M. (Mark), Abecasis, G.R. (Gonçalo), Adair, L.S. (Linda), Bakker, S.J.L. (Stephan), and Barroso, I.E. (Inês)
- Abstract
Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140mmg Hg systolic blood pressure ≥90mmg Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3 GUCY1B3, NPR3 C5orf23, ADM, FURIN FES, GOSR2, GNAS EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 geno
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- 2011
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8. The relationship between fertility and lifespan in humans
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Kuningas, M. (Maris), Altmäe, S. (Signe), Uitterlinden, A.G. (André), Hofman, A. (Albert), Tikka-Kleemola, P. (Päivi), Tiemeier, H.W. (Henning), Kuningas, M. (Maris), Altmäe, S. (Signe), Uitterlinden, A.G. (André), Hofman, A. (Albert), Tikka-Kleemola, P. (Päivi), and Tiemeier, H.W. (Henning)
- Abstract
Evolutionary theories of aging predict a trade-off between fertility and lifespan, where increased lifespan comes at the cost of reduced fertility. Support for this prediction has been obtained from various sources. However, which genes underlie this relationship is unknown. To assess it, we first analyzed the association of fertility with age at menarche and menopause
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- 2011
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9. A genome-wide association study of aging
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Walter, S. (Stefan), Atzmon, G. (Gil), Demerath, E.W. (Ellen), Garcia, M. (Melissa), Kaplan, R.C. (Robert), Kumari, M. (Meena), Lunetta, K.L. (Kathryn), Milaneschi, Y. (Yuri), Tanaka, T. (Toshiko), Tranah, G.J. (Gregory), Völker, U. (Uwe), Yu, L. (Lei), Arnold, A.M. (Alice), Benjamin, E.J. (Emelia), Biffar, R. (Reiner), Buchman, A.S. (Aron), Boerwinkle, E.A. (Eric), Couper, D. (David), Jager, P.L. (Philip) de, Evans, D.A. (Denis), Harris, T.B. (Tamara), Hoffmann, W. (Wolfgang), Hofman, A. (Albert), Karasik, D. (David), Kiel, D.P. (Douglas), Kocher, T. (Thomas), Kuningas, M. (Maris), Launer, L.J. (Lenore), Lohman, K. (Kurt), Lutsey, P.L. (Pamela), Mackenbach, J.P. (Johan), Marciante, K. (Kristin), Psaty, B.M. (Bruce), Reiman, E.M. (Eric), Rotter, J.I. (Jerome), Seshadri, S. (Sudha), Shardell, M.D. (Michelle), Smith, A.V. (Albert Vernon), Tikka-Kleemola, P. (Päivi), Walston, J. (Jeremy), Zillikens, M.C. (Carola), Bandinelli, S. (Stefania), Baumeister, S.E. (Sebastian), Bennett, D.A. (David), Ferrucci, L. (Luigi), Gudnason, V. (Vilmundur), Kivimaki, M. (Mika), Liu, Y. (YongMei), Murabito, J. (Joanne), Newman, A.B. (Anne), Tiemeier, H.W. (Henning), Franceschini, N. (Nora), Walter, S. (Stefan), Atzmon, G. (Gil), Demerath, E.W. (Ellen), Garcia, M. (Melissa), Kaplan, R.C. (Robert), Kumari, M. (Meena), Lunetta, K.L. (Kathryn), Milaneschi, Y. (Yuri), Tanaka, T. (Toshiko), Tranah, G.J. (Gregory), Völker, U. (Uwe), Yu, L. (Lei), Arnold, A.M. (Alice), Benjamin, E.J. (Emelia), Biffar, R. (Reiner), Buchman, A.S. (Aron), Boerwinkle, E.A. (Eric), Couper, D. (David), Jager, P.L. (Philip) de, Evans, D.A. (Denis), Harris, T.B. (Tamara), Hoffmann, W. (Wolfgang), Hofman, A. (Albert), Karasik, D. (David), Kiel, D.P. (Douglas), Kocher, T. (Thomas), Kuningas, M. (Maris), Launer, L.J. (Lenore), Lohman, K. (Kurt), Lutsey, P.L. (Pamela), Mackenbach, J.P. (Johan), Marciante, K. (Kristin), Psaty, B.M. (Bruce), Reiman, E.M. (Eric), Rotter, J.I. (Jerome), Seshadri, S. (Sudha), Shardell, M.D. (Michelle), Smith, A.V. (Albert Vernon), Tikka-Kleemola, P. (Päivi), Walston, J. (Jeremy), Zillikens, M.C. (Carola), Bandinelli, S. (Stefania), Baumeister, S.E. (Sebastian), Bennett, D.A. (David), Ferrucci, L. (Luigi), Gudnason, V. (Vilmundur), Kivimaki, M. (Mika), Liu, Y. (YongMei), Murabito, J. (Joanne), Newman, A.B. (Anne), Tiemeier, H.W. (Henning), and Franceschini, N. (Nora)
- Abstract
Human longevity and healthy aging show moderate heritability (20%-50%). We conducted a meta-analysis of genome-wide association studies from 9 studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium for 2 outcomes: (1) all-cause mortality, and (2) survival free of major disease or death. No single nucleotide polymorphism (SNP) was a genome-wide significant predictor of either outcome (p < 5 × 10-8). We found 14 independent SNPs that predicted risk of death, and 8 SNPs that predicted event-free survival (p < 10-5). These SNPs are in or near genes that are highly expressed in the brain (HECW2, HIP1, BIN2, GRIA1), genes involved in neural development and function (KCNQ4, LMO4, GRIA1, NETO1) and autophagy (ATG4C), and genes that are associated with risk of various diseases including cancer and Alzheimer's disease. In addition to considerable overlap between the traits, pathway and network analysis corroborated these findings. These findings indicate that variation in genes involved in neurological processes may be an important factor in regulating aging free of major disease and achieving longevity.
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- 2011
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10. Large common deletions associate with mortality at old age
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Kuningas, M. (Maris), Estrada Gil, K. (Karol), Hsu, Y.-H. (Yi-Hsiang), Nandakumar, K. (Kannabiran), Uitterlinden, A.G. (André), Lunetta, K.L. (Kathryn), Tikka-Kleemola, P. (Päivi), Karasik, D. (David), Hofman, A. (Albert), Murabito, J. (Joanne), Rivadeneira Ramirez, F. (Fernando), Kiel, D.P. (Douglas), Tiemeier, H.W. (Henning), Kuningas, M. (Maris), Estrada Gil, K. (Karol), Hsu, Y.-H. (Yi-Hsiang), Nandakumar, K. (Kannabiran), Uitterlinden, A.G. (André), Lunetta, K.L. (Kathryn), Tikka-Kleemola, P. (Päivi), Karasik, D. (David), Hofman, A. (Albert), Murabito, J. (Joanne), Rivadeneira Ramirez, F. (Fernando), Kiel, D.P. (Douglas), and Tiemeier, H.W. (Henning)
- Abstract
Copy-number variants (CNVs) are a source of genetic variation that increasingly are associated with human disease. However, the role of CNVs in human lifespan is to date unknown. To identify CNVs that influence mortality at old age, we analyzed genome-wide CNV data in 5178 participants of Rotterdam Study (RS1) and positive findings were evaluated in 1714 participants of the second cohort of the Rotterdam Study (RS2) and in 4550 participants of Framingham Heart Study (FHS). First, we assessed the total burden of rare (frequency <1%) and common (frequency >1%) CNVs for association with mortality during follow-up. These analyses were repeated by stratifying CNVs by type and size. Secondly, we assessed individual comm
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- 2011
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11. Strengthening the reporting of genetic risk prediction studies (GRIPS): Explanation and elaboration
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Janssens, A.C.J.W. (Cécile), Ioannidis, J.P.A. (John), Bedrosian, S. (Sara), Boffetta, P. (Paolo), Dolan, S.M. (Siobhan M.), Dowling, N. (Nicole), Fortier, I. (Isabel), Freedman, A.N. (Andrew Nathan), Grimshaw, J. (Jeremy), Gulcher, J.R. (Jeffrey), Gwinn, M. (Marta), Hlatky, M.A. (Mark), Janes, H. (Holly), Kraft, P. (Peter), Melillo, S. (Stephanie), O'Donnell, C.J. (Christopher), Pencina, M.J. (Michael), Ransohoff, D. (David), Schully, S.D. (Sheri), Seminara, D. (Daniela), Winn, D.M. (Deborah), Wright, C.F. (Caroline), Tikka-Kleemola, P. (Päivi), Little, J. (Julian), Khoury, M.J. (Muin Joseph), Janssens, A.C.J.W. (Cécile), Ioannidis, J.P.A. (John), Bedrosian, S. (Sara), Boffetta, P. (Paolo), Dolan, S.M. (Siobhan M.), Dowling, N. (Nicole), Fortier, I. (Isabel), Freedman, A.N. (Andrew Nathan), Grimshaw, J. (Jeremy), Gulcher, J.R. (Jeffrey), Gwinn, M. (Marta), Hlatky, M.A. (Mark), Janes, H. (Holly), Kraft, P. (Peter), Melillo, S. (Stephanie), O'Donnell, C.J. (Christopher), Pencina, M.J. (Michael), Ransohoff, D. (David), Schully, S.D. (Sheri), Seminara, D. (Daniela), Winn, D.M. (Deborah), Wright, C.F. (Caroline), Tikka-Kleemola, P. (Päivi), Little, J. (Julian), and Khoury, M.J. (Muin Joseph)
- Abstract
The rapid and continuing progress in gene discovery for complex diseases is fueling interest in the potential application of genetic risk models for clinical and public health practice. The number of studies assessing the predictive ability is steadily increasing, but they vary widely in completeness of reporting and apparent quality. Transparent reporting of the strengths and weaknesses of these studies is important to facilitate the accumulation of evidence on genetic risk prediction. A multidisciplinary workshop sponsored by the Human Genome Epidemiology Network developed a checklist of 25 items recommended for strengthening the reporting of Genetic RIsk Prediction Studies (GRIPS), building on the principles established by previous reporting guidelines. These recommendations aim to enhance the transparency, quality and comple
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- 2011
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12. Association of HSP70 and its co-chaperones with Alzheimer's disease
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Broer, L. (Linda), Ikram, M.A. (Arfan), Schuur, M. (Maaike), DeStefano, A.L. (Anita), Bis, J.C. (Joshua), Liu, F. (Fan), Rivadeneira Ramirez, F. (Fernando), Uitterlinden, A.G. (André), Beiser, A. (Alexa), Longstreth Jr, W.T., Hofman, A. (Albert), Aulchenko, Y.S. (Yurii), Seshadri, S. (Sudha), Fitzpatrick, A.L. (Annette), Oostra, B.A. (Ben), Breteler, M.M.B. (Monique), Tikka-Kleemola, P. (Päivi), Broer, L. (Linda), Ikram, M.A. (Arfan), Schuur, M. (Maaike), DeStefano, A.L. (Anita), Bis, J.C. (Joshua), Liu, F. (Fan), Rivadeneira Ramirez, F. (Fernando), Uitterlinden, A.G. (André), Beiser, A. (Alexa), Longstreth Jr, W.T., Hofman, A. (Albert), Aulchenko, Y.S. (Yurii), Seshadri, S. (Sudha), Fitzpatrick, A.L. (Annette), Oostra, B.A. (Ben), Breteler, M.M.B. (Monique), and Tikka-Kleemola, P. (Päivi)
- Abstract
The heat shock protein (HSP) 70 family has been implicated in the pathology of Alzheimer's disease (AD). In this study, we examined common genetic variations in the 80 genes encoding HSP70 and its co-chaperones. We conducted a study in a series of
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- 2011
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13. Association of heat shock proteins with Parkinson's disease
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Broer, L. (Linda), Koudstaal, P.J. (Peter), Amin, N. (Najaf), Rivadeneira Ramirez, F. (Fernando), Uitterlinden, A.G. (André), Hofman, A. (Albert), Oostra, B.A. (Ben), Breteler, M.M.B. (Monique), Ikram, M.A. (Arfan), Tikka-Kleemola, P. (Päivi), Broer, L. (Linda), Koudstaal, P.J. (Peter), Amin, N. (Najaf), Rivadeneira Ramirez, F. (Fernando), Uitterlinden, A.G. (André), Hofman, A. (Albert), Oostra, B.A. (Ben), Breteler, M.M.B. (Monique), Ikram, M.A. (Arfan), and Tikka-Kleemola, P. (Päivi)
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- 2011
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14. PredictABEL: An R package for the assessment of risk prediction models
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Kundu, S. (Suman), Aulchenko, Y.S. (Yurii), Tikka-Kleemola, P. (Päivi), Janssens, A.C.J.W. (Cécile), Kundu, S. (Suman), Aulchenko, Y.S. (Yurii), Tikka-Kleemola, P. (Päivi), and Janssens, A.C.J.W. (Cécile)
- Abstract
The rapid identification of genetic markers for multifactorial diseases from genome-wide association studies is fuelling interest in investigating the predictive ability and health care utility of genetic risk models. Various measures are available for the assessment of risk prediction models, each addressing a different aspect of performance and utility. We developed PredictABEL, a package in R that covers descriptive tables, measures and figures that are used in the analysis of risk prediction studies such as measures of model fit, predictive ability and clinical utility, and risk distributions, calibration plot and the receiver operating characteristic plot. Tables and figures are saved as separate files in a user-specified format, which include publicationquality EPS and TIFF formats. All figures are available in a ready-made layout, but they can be customized to the preferences of the user. The package has been developed for the analysis of genetic risk prediction studies, but can also be used for studies that only include non-genetic risk factors. PredictABELis freely available at the websites of GenABEL (http://www.genabel.org) and CRAN (http://cran.r-project.org/).
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- 2011
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15. Perspectives on the use of multiple sclerosis risk genes for prediction
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Jafari, N. (Naghmeh), Broer, L. (Linda), Tikka-Kleemola, P. (Päivi), Janssens, A.C.J.W. (Cécile), Hintzen, R.Q. (Rogier), Jafari, N. (Naghmeh), Broer, L. (Linda), Tikka-Kleemola, P. (Päivi), Janssens, A.C.J.W. (Cécile), and Hintzen, R.Q. (Rogier)
- Abstract
Objective: A recent collaborative genome-wide association study replicated a large number of susceptibility loci and identified novel loci. This increase in known multiple sclerosis (MS) risk genes raises questions about clinical applicability of genotyping. In an empirical set we assessed the predictive power of typing multiple genes. Next, in a modelling study we explored current and potential predictive performance of genetic MS risk models. Materials and Methods: Genotype data on 6 MS risk genes in 591 MS patients and 600 controls were used to investigate the predictive value of combining risk alleles. Next, the replicated and novel MS risk loci from the recent and largest international genome-wide association study were used to construct genetic risk models simulating a population of 100,000 individuals. Finally, we assessed the required numbers, frequencies, and ORs of risk SNPs for higher discriminative accuracy in the future. Results: Individuals with 10 to 12 risk alleles had a significantly increased risk compared to individuals with the average population risk for developing MS (OR 2.76 (95% CI 2.02-3.77)). In the simulation study we showed that the area under the receiver operating characteristic curve (AUC) for a risk score based on the 6 SNPs was 0.64. The AUC increases to 0.66 using the well replicated 24 SNPs and to 0.69 when including all replicated and novel SNPs (n = 53) in the risk model. An additional 20 SNPs with allele frequency 0.30 and ORs 1.1 would be needed to increase the AUC to a slightly higher level of 0.70, and at least 50 novel variants with allele frequency 0.30 and ORs 1.4 would be needed to obtain an AUC of 0.85. Conclusion: Although new MS risk SNPs emerge rapidly, the discriminatory ability in a clinical setting will be limited.
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- 2011
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16. A polymorphism in the regulatory region of PRNP is associated with increased risk of sporadic Creutzfeldt-Jakob disease
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Sanchez-Juan, P. (Pascual), Bishop, M.T. (Matthew), Croes, E.A. (Esther), Knight, R.S.G. (Richard), Will, R.G., Tikka-Kleemola, P. (Päivi), Manson, J.C. (Jean), Sanchez-Juan, P. (Pascual), Bishop, M.T. (Matthew), Croes, E.A. (Esther), Knight, R.S.G. (Richard), Will, R.G., Tikka-Kleemola, P. (Päivi), and Manson, J.C. (Jean)
- Abstract
Background: Creutzfeldt-Jakob disease (CJD) is a rare transmissible neurodegenerative disorder. An important determinant for CJD risk and phenotype is the M129V polymorphism of the human prion protein gene (PRNP), but there are also other coding and non-coding polymorphisms inside this gene.Methods: We tested whether three non-coding polymorphism located inside the PRNP regulatory region (C-101G, G310C and T385C) were associated with risk of CJD and with age at onset in a United Kingdom population-based sample of 131 sporadic CJD (sCJD) patients and 194 controls.Results: We found no disease association for either PRNP C-101G or PRNP T385C. Although the crude analysis did not show a significant association between PRNP G310C and sCJD (OR: 1.5; 95%CI = 0.7 to 2.9), after adjusting by PRNP M129V genotype, it resulted that being a C allele carrier at PRNP G310C was significantly (p = 0.03) associated with a 2.4 fold increased risk of developing sCJD (95%CI = 1.1 to 5.4). Additionally, haplotypes carrying PRNP 310C coupled with PRNP 129M were significantly overrepresented in patients (p = 0.02) compared to controls. Cases of sCJD carrying a PRNP 310C allele presented at a younger age (on average 8.9 years younger than those without this allele), which was of statistical significance (p = 0.05). As expected, methionine and valine homozygosity at PRNP M129V increased significantly the risk of sCJD, alone and adjusted by PRNP G310C (OR MM/MV = 7.3; 95%CI 3.9 to 13.5 and OR VV/MV = 4.0; 95%CI 1.7 to 9.3).Conclusions: Our findings support the hypothesis that genetic variations in the PRNP promoter may have a role in the pathogenesis of sCJD.
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- 2011
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17. Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration
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Yu, Y. (Yi), Bhangale, T. (Tushar), Fagerness, J. (Jesen), Ripke, S. (Stephan), Thorleifsson, G. (Gudmar), Tan, P.L. (Perciliz), Souied, E.H. (Eric), Richardson, A.J. (Andrea), Merriam, J.E. (Joanna), Buitendijk, G.H.S. (Gabrielle), Reynolds, R. (Robyn), Raychaudhuri, S. (Soumya), Chin, K.A. (Kimberly), Sobrin, L. (Lucia), Evangelou, E. (Evangelos), Lee, P.H. (Phil), Leveziel, N. (Nicolas), Zack, D.J. (Donald), Campochiaro, B. (Betsy), Smith, R.T. (Theodore), Barile, G.R. (Gaetano), Guymer, R.H. (Robyn), Hogg, R. (Ruth), Chakravarthy, U. (Usha), Robman, L.D. (Luba), Gustafsson, O. (Omar), Sigurdsson, H. (Haraldur), Ortmann, W. (Ward), Behrens, T.W. (Timothy), Stefansson, K. (Kari), Uitterlinden, A.G. (André), Tikka-Kleemola, P. (Päivi), Vingerling, J.R. (Hans), Klaver, C.C.W. (Caroline), Allikmets, R. (Rando), Brantley, M.A. (Milam), Baird, P.N. (Paul), Katsanis, N. (Nicholas), Thorsteinsdottir, U. (Unnur), Ioannidis, J.P.A. (John), Daly, M.J. (Mark), Graham, R.R. (Robert), Seddon, J.M. (Johanna), Yu, Y. (Yi), Bhangale, T. (Tushar), Fagerness, J. (Jesen), Ripke, S. (Stephan), Thorleifsson, G. (Gudmar), Tan, P.L. (Perciliz), Souied, E.H. (Eric), Richardson, A.J. (Andrea), Merriam, J.E. (Joanna), Buitendijk, G.H.S. (Gabrielle), Reynolds, R. (Robyn), Raychaudhuri, S. (Soumya), Chin, K.A. (Kimberly), Sobrin, L. (Lucia), Evangelou, E. (Evangelos), Lee, P.H. (Phil), Leveziel, N. (Nicolas), Zack, D.J. (Donald), Campochiaro, B. (Betsy), Smith, R.T. (Theodore), Barile, G.R. (Gaetano), Guymer, R.H. (Robyn), Hogg, R. (Ruth), Chakravarthy, U. (Usha), Robman, L.D. (Luba), Gustafsson, O. (Omar), Sigurdsson, H. (Haraldur), Ortmann, W. (Ward), Behrens, T.W. (Timothy), Stefansson, K. (Kari), Uitterlinden, A.G. (André), Tikka-Kleemola, P. (Päivi), Vingerling, J.R. (Hans), Klaver, C.C.W. (Caroline), Allikmets, R. (Rando), Brantley, M.A. (Milam), Baird, P.N. (Paul), Katsanis, N. (Nicholas), Thorsteinsdottir, U. (Unnur), Ioannidis, J.P.A. (John), Daly, M.J. (Mark), Graham, R.R. (Robert), and Seddon, J.M. (Johanna)
- Abstract
Despite significant progress in the identification of genetic loci for age-related macular degeneration (AMD), not all of the heritability has been explained. To identify variants which contribute to the remaining genetic susceptibility, we performed the largest meta-analysis of genome-wide association studies to date for advanced AMD. We imputed 6 036 699 single-nucleotide polymorphisms with the 1000 Genomes Project reference genotypes on 2594 cases and 4134 controls with follow-up replication of top signals in 5640 cases and 52 174 controls. We identified two new common susceptibility alleles, rs1999930 on 6q21-q22.3 near FRK/COL10A1 [odds ratio (OR) 0.87; P 5 1.1 × 10-8] and rs4711751 on 6p12 near VEGFA (OR 1.15; P 5 8.7 × 10-9). In addition to the two novel loci, 10 previously reported loci in ARMS2/HTRA1 (rs10490924), CFH (rs1061170, and rs1410996), CFB (rs641153), C3 (rs2230199), C2 (rs9332739), CFI (rs10033900), LIPC (rs10468017), TIMP3 (rs9621532) and CETP (rs3764261) were confirmed with genomewide significant signals in this large study. Loci in the recently reported genes ABCA1 and COL8A1 were also detected with suggestive evidence of association with advanced AMD. The novel variants identified in this study suggest that angiogenesis (VEGFA) and extracellular collagen matrix (FRK/COL10A1) pathways contribute to the development of advanced AMD.
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- 2011
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18. Genome-wide association studies in Asians confirm the involvement of ATOH7 and TGFBR3, and further identify CARD10 as a novel locus influencing optic discarea
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Khor, C.C., Ramdas, W.D. (Wishal), Vithana, E.N. (Eranga), Cornes, B.K. (Belinda), Sim, X. (Xueling), Tay, W.-T., Saw, S-M. (Seang-Mei), Lavanya, Y.Z., Wu, R. (Renyi), Wang, J.J. (Jie Jin), Mitchell, P. (Paul), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Teo, Y.-Y., Chia, K.-S., Seielstad, M. (Mark), Hibberd, M.L. (Martin), Vingerling, J.R. (Hans), Klaver, C.C.W. (Caroline), Jansonius, N.M. (Nomdo), Tai, E.S. (Shyong), Wong, T.Y. (Tien Yin), Tikka-Kleemola, P. (Päivi), Aung, T. (Tin), Khor, C.C., Ramdas, W.D. (Wishal), Vithana, E.N. (Eranga), Cornes, B.K. (Belinda), Sim, X. (Xueling), Tay, W.-T., Saw, S-M. (Seang-Mei), Lavanya, Y.Z., Wu, R. (Renyi), Wang, J.J. (Jie Jin), Mitchell, P. (Paul), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Teo, Y.-Y., Chia, K.-S., Seielstad, M. (Mark), Hibberd, M.L. (Martin), Vingerling, J.R. (Hans), Klaver, C.C.W. (Caroline), Jansonius, N.M. (Nomdo), Tai, E.S. (Shyong), Wong, T.Y. (Tien Yin), Tikka-Kleemola, P. (Päivi), and Aung, T. (Tin)
- Abstract
Damage to the optic nerve (e.g. from glaucoma) has an adverse and often irreversible impact on vision. Earlier studies have suggested that the size of the optic nerve head could be governed by hereditary factors. We conducted a genome-wide association study (GWAS) on 4445 Singaporean individuals (n 5 2132 of Indian and n 5 2313 of Malay ancestry, respectively), with replication in Rotterdam, the Netherlands (n 5 9326 individuals of Caucasian ancestry) using the most widely reported parameter for optic disc traits, the optic disc area. We identified a novel locus on chromosome 22q13.1, CARD10, which strongly associates with optic disc area in both Singaporean cohorts as well as in the Rotterdam Study (RS; rs9607469, perallele change in optic disc area 5 0.051 mm2; Pmeta5 2.73310-12) and confirmed the association between CDC7/TGFBR3 (lead single nucleotide polymorphism (SNP) rs1192415, Pmeta5 7.57310-17) and ATOH7 (lead SNP rs7916697, Pmeta5 2.00 3 10-15) and optic disc area in Asians. This is the first Asian-based GWAS on optic disc area, identifying a novel locus for the optic disc area, but also confirming the results found in Caucasian persons suggesting that there are general genetic determinants applicable to the size of the optic disc across different ethnicities.
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- 2011
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19. Multiple loci are associated with white blood cell phenotypes
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Nalls, M.A. (Michael), Couper, D. (David), Tanaka, T. (Toshiko), Rooij, F.J.A. (Frank) van, Chen, M-H. (Ming-Huei), Smith, A.V. (Albert Vernon), Toniolo, D. (Daniela), Zakai, N.A. (Neil), Yang, Q. (Qiong Fang), Greinacher, A. (Andreas), Wood, A.R. (Andrew), Garcia, M. (Melissa), Gasparini, P. (Paolo), Liu, Y. (YongMei), Lumley, T. (Thomas), Folsom, A.R. (Aaron), Reiner, A.P. (Alex), Gieger, C. (Christian), Lagou, V. (Vasiliki), Felix, J.F. (Janine), Völzke, H. (Henry), Gouskova, N.A. (Natalia), Biffi, A. (Alessandro), Döring, A. (Angela), Völker, U. (Uwe), Chong, S. (Sean), Wiggins, K.L. (Kerri), Rendon, A. (Augusto), Dehghan, A. (Abbas), Moore, M. (Matt), Taylor, K.D. (Kent), Wilson, J.G. (James), Lettre, G. (Guillaume), Hofman, A. (Albert), Bis, J.C. (Joshua), Pirastu, N. (Nicola), Fox, C.S. (Caroline), Meisinger, C. (Christa), Sambrook, J.G. (Jennifer), Arepalli, S. (Sampath), Nauck, M. (Matthias), Prokisch, H. (Holger), Stephens, J. (Jonathan), Glazer, N.L. (Nicole), Cupples, L.A. (Adrienne), Okada, Y. (Yukinori), Takahashi, A. (Atsushi), Kamatani, Y. (Yoichiro), Matsuda, K. (Koichi), Tsunoda, T. (Tatsuhiko), Kubo, M. (Michiaki), Nakamura, Y. (Yusuke), Yamamoto, K. (Kazuhiko), Stumvoll, M. (Michael), Tönjes, A. (Anke), Prokopenko, I. (Inga), Illig, T. (Thomas), Patel, K.V. (Kushang), Garner, S.F. (Stephen), Kuhnel, B. (Brigitte), Mangino, M. (Massimo), Oostra, B.A. (Ben), Thein, S.L., Coresh, J. (Josef), Wichmann, H.E. (Heinz Erich), Menzel, S. (Stephan), Lin, J., Pistis, G. (Giorgio), Uitterlinden, A.G. (André), Spector, T.D. (Timothy), Teumer, A. (Alexander), Eiriksdottir, G. (Gudny), Gudnason, V. (Vilmundur), Bandinelli, S. (Stefania), Frayling, T.M. (Timothy), Chakravarti, A. (Aravinda), Tikka-Kleemola, P. (Päivi), Melzer, D. (David), Ouwehand, W.H. (Willem), Levy, D. (Daniel), Boerwinkle, E.A. (Eric), Singleton, A. (Andrew), Hernandez, D.G. (Dena), Longo, D.L. (Dan), Soranzo, N. (Nicole), Witteman, J.C.M. (Jacqueline), Psaty, B.M. (Bruce), Ferrucci, L. (Luigi), Harris, T.B. (Tamara), O'Donnell, C.J. (Christopher), Ganesh, S.K. (Santhi), Nalls, M.A. (Michael), Couper, D. (David), Tanaka, T. (Toshiko), Rooij, F.J.A. (Frank) van, Chen, M-H. (Ming-Huei), Smith, A.V. (Albert Vernon), Toniolo, D. (Daniela), Zakai, N.A. (Neil), Yang, Q. (Qiong Fang), Greinacher, A. (Andreas), Wood, A.R. (Andrew), Garcia, M. (Melissa), Gasparini, P. (Paolo), Liu, Y. (YongMei), Lumley, T. (Thomas), Folsom, A.R. (Aaron), Reiner, A.P. (Alex), Gieger, C. (Christian), Lagou, V. (Vasiliki), Felix, J.F. (Janine), Völzke, H. (Henry), Gouskova, N.A. (Natalia), Biffi, A. (Alessandro), Döring, A. (Angela), Völker, U. (Uwe), Chong, S. (Sean), Wiggins, K.L. (Kerri), Rendon, A. (Augusto), Dehghan, A. (Abbas), Moore, M. (Matt), Taylor, K.D. (Kent), Wilson, J.G. (James), Lettre, G. (Guillaume), Hofman, A. (Albert), Bis, J.C. (Joshua), Pirastu, N. (Nicola), Fox, C.S. (Caroline), Meisinger, C. (Christa), Sambrook, J.G. (Jennifer), Arepalli, S. (Sampath), Nauck, M. (Matthias), Prokisch, H. (Holger), Stephens, J. (Jonathan), Glazer, N.L. (Nicole), Cupples, L.A. (Adrienne), Okada, Y. (Yukinori), Takahashi, A. (Atsushi), Kamatani, Y. (Yoichiro), Matsuda, K. (Koichi), Tsunoda, T. (Tatsuhiko), Kubo, M. (Michiaki), Nakamura, Y. (Yusuke), Yamamoto, K. (Kazuhiko), Stumvoll, M. (Michael), Tönjes, A. (Anke), Prokopenko, I. (Inga), Illig, T. (Thomas), Patel, K.V. (Kushang), Garner, S.F. (Stephen), Kuhnel, B. (Brigitte), Mangino, M. (Massimo), Oostra, B.A. (Ben), Thein, S.L., Coresh, J. (Josef), Wichmann, H.E. (Heinz Erich), Menzel, S. (Stephan), Lin, J., Pistis, G. (Giorgio), Uitterlinden, A.G. (André), Spector, T.D. (Timothy), Teumer, A. (Alexander), Eiriksdottir, G. (Gudny), Gudnason, V. (Vilmundur), Bandinelli, S. (Stefania), Frayling, T.M. (Timothy), Chakravarti, A. (Aravinda), Tikka-Kleemola, P. (Päivi), Melzer, D. (David), Ouwehand, W.H. (Willem), Levy, D. (Daniel), Boerwinkle, E.A. (Eric), Singleton, A. (Andrew), Hernandez, D.G. (Dena), Longo, D.L. (Dan), Soranzo, N. (Nicole), Witteman, J.C.M. (Jacqueline), Psaty, B.M. (Bruce), Ferrucci, L. (Luigi), Harris, T.B. (Tamara), O'Donnell, C.J. (Christopher), and Ganesh, S.K. (Santhi)
- Abstract
White blood cell (WBC) count is a common clinical measure from complete blood count assays, and it varies widely among healthy individuals. Total WBC count and its constituent subtypes have been shown to be moderately heritable, with the heritability estimates varying across cell types. We studied 19,509 subjects from seven cohorts in a discovery analysis, and 11,823 subjects from ten cohorts for replication analyses, to determine genetic factors influencing variability within the normal hematological range for total WBC count and five WBC subtype measures. Cohort specific data was supplied by the CHARGE, HeamGen, and INGI consortia, as well as independent collaborative studies. We identified and replicated ten associations with total WBC count and five WBC subtypes at seven different genomic loci (total WBC count-6p21 in the HLA region, 17q21 near ORMDL3, and CSF3; neutrophil count-17q21; basophil count-3p21 near RPN1 and C3orf27; lymphocyte count-6p21, 19p13 at EPS15L1; monocyte count-2q31 at ITGA4, 3q21, 8q24 an intergenic region, 9q31 near EDG2), including three previously reported associations and seven novel associations. To investigate functional relationships among variants contributing to variability in the six WBC traits, we utilized gene expression- and pathways-based analyses. We implemented gene-clustering algorithms to evaluate functional connectivity among implicated loci and showed functional relationships across cell types. Gene expression data from whole blood was utilized to show that significant biological consequences can be extracted from our genome-wide analyses, with effect estimates for significant loci from the meta-analyses being highly corellated with the proximal gene expression. In addition, collaborative efforts between the groups contributing to this study and related studies conducted by the COGENT and RIKEN groups allowed for the examination of effect homogeneity for genome-wide significant associations across populations of diverse
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- 2011
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20. A genome-wide screen for interactions reveals a new locus on 4p15 modifying the effect of waist-to-hip ratio on total cholesterol
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Surakka, I. (Ida), Isaacs, A.J. (Aaron), Karssen, L.C. (Lennart), Laurila, P.-P.P., Middelberg, R.P.S. (Rita), Tikkanen, E. (Emmi), Ried, J.S. (Janina), Lamina, C. (Claudia), Mangino, M. (Massimo), Igl, W. (Wilmar), Hottenga, J.J. (Jouke Jan), Lagou, V. (Vasiliki), Harst, P. (Pim) van der, Leach, I.M. (Irene Mateo), Esko, T. (Tõnu), Kutalik, Z. (Zoltán), Wainwright, N.W. (Nicholas), Struchalin, M.V. (Maksim), Sarin, A.-P., Kangas, A.J. (Antti), Viikari, J. (Jorma), Perola, M. (Markus), Rantanen, T. (Taina), Petersen, A.K., Soininen, P. (Pasi), Johansson, A. (Åsa), Soranzo, N. (Nicole), Heath, A.C. (Andrew), Papamarkou, T. (Theodore), Prokopenko, I. (Inga), Tönjes, A. (Anke), Kronenberg, F. (Florian), Döring, A. (Angela), Rivadeneira Ramirez, F. (Fernando), Montgomery, G.W. (Grant), Whitfield, J.B. (John), Kähönen, M. (Mika), Lehtimäki, T. (Terho), Freimer, N.B. (Nelson), Willemsen, G.A.H.M. (Gonneke), Geus, E.J.C. (Eco) de, Palotie, A. (Aarno), Sandhu, M.S. (Manj), Waterworth, D. (Dawn), Metspalu, A. (Andres), Stumvoll, M. (Michael), Uitterlinden, A.G. (André), Jula, A. (Antti), Navis, G. (Gerjan), Wijmenga, C. (Cisca), Wolffenbuttel, B.H.R. (Bruce), Taskinen, M.-R., Ala-Korpela, M. (Mika), Kaprio, J. (Jaakko), Kyvik, K.O. (Kirsten Ohm), Boomsma, D.I. (Dorret), Pedersen, N.L. (Nancy), Gyllensten, U. (Ulf), Wilson, J.F. (James), Rudan, I. (Igor), Campbell, H. (Harry), Pramstaller, P.P. (Peter Paul), Spector, T.D. (Timothy), Witteman, J.C.M. (Jacqueline), Eriksson, J.G. (Johan), Salomaa, V. (Veikko), Oostra, B.A. (Ben), Raitakari, O. (Olli), Wichmann, H.E. (Heinz Erich), Gieger, C. (Christian), Järvelin, M.R., Martin, N.G. (Nicholas), Hofman, A. (Albert), McCarthy, M.I. (Mark), Aulchenko, Y.S. (Yurii), Peltonen, L. (Leena Johanna), Tikka-Kleemola, P. (Päivi), Ripatti, S. (Samuli), Surakka, I. (Ida), Isaacs, A.J. (Aaron), Karssen, L.C. (Lennart), Laurila, P.-P.P., Middelberg, R.P.S. (Rita), Tikkanen, E. (Emmi), Ried, J.S. (Janina), Lamina, C. (Claudia), Mangino, M. (Massimo), Igl, W. (Wilmar), Hottenga, J.J. (Jouke Jan), Lagou, V. (Vasiliki), Harst, P. (Pim) van der, Leach, I.M. (Irene Mateo), Esko, T. (Tõnu), Kutalik, Z. (Zoltán), Wainwright, N.W. (Nicholas), Struchalin, M.V. (Maksim), Sarin, A.-P., Kangas, A.J. (Antti), Viikari, J. (Jorma), Perola, M. (Markus), Rantanen, T. (Taina), Petersen, A.K., Soininen, P. (Pasi), Johansson, A. (Åsa), Soranzo, N. (Nicole), Heath, A.C. (Andrew), Papamarkou, T. (Theodore), Prokopenko, I. (Inga), Tönjes, A. (Anke), Kronenberg, F. (Florian), Döring, A. (Angela), Rivadeneira Ramirez, F. (Fernando), Montgomery, G.W. (Grant), Whitfield, J.B. (John), Kähönen, M. (Mika), Lehtimäki, T. (Terho), Freimer, N.B. (Nelson), Willemsen, G.A.H.M. (Gonneke), Geus, E.J.C. (Eco) de, Palotie, A. (Aarno), Sandhu, M.S. (Manj), Waterworth, D. (Dawn), Metspalu, A. (Andres), Stumvoll, M. (Michael), Uitterlinden, A.G. (André), Jula, A. (Antti), Navis, G. (Gerjan), Wijmenga, C. (Cisca), Wolffenbuttel, B.H.R. (Bruce), Taskinen, M.-R., Ala-Korpela, M. (Mika), Kaprio, J. (Jaakko), Kyvik, K.O. (Kirsten Ohm), Boomsma, D.I. (Dorret), Pedersen, N.L. (Nancy), Gyllensten, U. (Ulf), Wilson, J.F. (James), Rudan, I. (Igor), Campbell, H. (Harry), Pramstaller, P.P. (Peter Paul), Spector, T.D. (Timothy), Witteman, J.C.M. (Jacqueline), Eriksson, J.G. (Johan), Salomaa, V. (Veikko), Oostra, B.A. (Ben), Raitakari, O. (Olli), Wichmann, H.E. (Heinz Erich), Gieger, C. (Christian), Järvelin, M.R., Martin, N.G. (Nicholas), Hofman, A. (Albert), McCarthy, M.I. (Mark), Aulchenko, Y.S. (Yurii), Peltonen, L. (Leena Johanna), Tikka-Kleemola, P. (Päivi), and Ripatti, S. (Samuli)
- Abstract
Recent genome-wide association (GWA) studies described 95 loci controlling serum lipid levels. These common variants explain ~25% of the heritability of the phenotypes. To date, no unbiased screen for gene-environment interactions for circulating lipids has been reported. We screened for variants that modify the relationship between known epidemiological risk factors and circulating lipid levels in a meta-analysis of genome-wide association (GWA) data from 18 population-based cohorts with European ancestry (maximum N = 32,225). We collected 8 further cohorts (N = 17,102) for replication, and rs6448771 on 4p15 demonstrated genome-wide significant interaction with waist-to-hip-ratio (WHR) on total cholesterol (TC) with a combined P-value of 4.79×10-9. There were two potential candidate genes in the region, PCDH7 and CCKAR, with differential expression levels for rs6448771 genotypes in adipose tissue. The effect of WHR on TC was strongest for individuals carrying two copies of G allele, for whom a one standard deviation (sd) difference in WHR corresponds to 0.19 sd difference in TC concentration, while for A allele homozygous the difference was 0.12 sd. Our findings may open up possibilities for targeted intervention strategies for people characterized by specific genomic profiles. However, more refined measures of both body-fat distribution and metabolic measures are needed to understand how their joint dynamics are modified by the newly found locus.
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- 2011
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21. Meta-analysis of genome-wide association for migraine in six population-based European cohorts
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Ligthart, L. (Lannie), Vries, B. (Boukje) de, Smith, A.V. (Albert Vernon), Ikram, M.A. (Arfan), Amin, N. (Najaf), Hottenga, J.J. (Jouke Jan), Koelewijn, S.C. (Stephany C.), Kattenberg, V.M. (Mathijs), Moor, M.H.M. de, Janssens, A.C.J.W. (Cécile), Aulchenko, Y.S. (Yurii), Oostra, B.A. (Ben), Geus, E.J.C. (Eco) de, Smit, J.H. (Johannes), Zitman, F.G. (Frans), Uitterlinden, A.G. (André), Hofman, A. (Albert), Willemsen, G.A.H.M. (Gonneke), Nyholt, D.R. (Dale), Montgomery, G.W. (Grant), Terwindt, G.M. (Gisela), Gudnason, V. (Vilmundur), Penninx, B.W.J.H. (Brenda), Breteler, L.M.T. (Leonie), Ferrari, M.D. (Michel), Launer, L.J. (Lenore), Tikka-Kleemola, P. (Päivi), Maagdenberg, A.M.J.M. (Arn) van den, Boomsma, D.I. (Dorret), Ligthart, L. (Lannie), Vries, B. (Boukje) de, Smith, A.V. (Albert Vernon), Ikram, M.A. (Arfan), Amin, N. (Najaf), Hottenga, J.J. (Jouke Jan), Koelewijn, S.C. (Stephany C.), Kattenberg, V.M. (Mathijs), Moor, M.H.M. de, Janssens, A.C.J.W. (Cécile), Aulchenko, Y.S. (Yurii), Oostra, B.A. (Ben), Geus, E.J.C. (Eco) de, Smit, J.H. (Johannes), Zitman, F.G. (Frans), Uitterlinden, A.G. (André), Hofman, A. (Albert), Willemsen, G.A.H.M. (Gonneke), Nyholt, D.R. (Dale), Montgomery, G.W. (Grant), Terwindt, G.M. (Gisela), Gudnason, V. (Vilmundur), Penninx, B.W.J.H. (Brenda), Breteler, L.M.T. (Leonie), Ferrari, M.D. (Michel), Launer, L.J. (Lenore), Tikka-Kleemola, P. (Päivi), Maagdenberg, A.M.J.M. (Arn) van den, and Boomsma, D.I. (Dorret)
- Abstract
Migraine is a common neurological disorder with a genetically complex background. This paper describes a meta-analysis of genome-wide association (GWA) studies on migraine, performed by the Dutch-Icelandic migraine genetics (DICE) consortium, which brings together six population-based European migra
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- 2011
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22. Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption
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Schumann, G. (Gunter), Coin, L. (Lachlan), Lourdusamy, A. (Anbarasu), Charoen, P. (Pimphen), Berger, K.H. (Karen), Stacey, D. (David), Desrivières, S. (Sylvane), Aliev, F.A. (Fazil), Khan, A.A. (Anokhi), Amin, N. (Najaf), Bakalkin, G. (Georgy), Balkau, B. (Beverley), Beulens, J.W.J. (Joline), Bilbao, A. (Ainhoa), Boer, R.A. (Rudolf) de, Beury, D. (Delphine), Bots, M.L. (Michiel), Breetvelt, E.J. (Elemi), Cauchi, S. (Stephane), Cavalcanti-Proença, C. (Christine), Chambers, J.C. (John), Clarke, T.-K., Dahmen, N. (N.), Geus, E.J.C. (Eco) de, Dick, D. (Danielle), Ducci, F. (Francesca), Easton, A. (Alanna), Edenberg, H.J. (Howard), Esk, T. (Tõnu), Fernández-Medarde, A. (Alberto), Foroud, T. (Tatiana), Freimer, N.B. (Nelson), Girault, J.-A., Grobbee, D.E. (Diederick), Guarrera, S. (Simonetta), Gudbjartsson, D.F. (Daniel), Hartikainen, A.L., Heath, A.C. (Andrew), Hesselbrock, V. (Victor), Hofman, A. (Albert), Hottenga, J.J. (Jouke Jan), Isohanni, M.K. (Matti), Kaprio, J. (Jaakko), Khaw, K-T. (Kay-Tee), Kuehnel, B. (Brigitte), Laitinen, J. (Jaana), Lobbens, S. (Stéphane), Luan, J., Mangino, M. (Massimo), Maroteaux, M. (Matthieu), Matullo, G. (Giuseppe), McCarthy, M.I. (Mark), Mueller, C. (Christian), Navis, G. (Gerjan), Numans, M.E. (Mattijs), Núñez, A.M. (Alejandro), Nyholt, D.R. (Dale), Onland-Moret, N.C. (Charlotte), Oostra, B.A. (Ben), O'Reilly, P.F. (Paul), Palkovits, M. (Miklos), Penninx, B.W.J.H. (Brenda), Polidoro, S. (Silvia), Pouta, A. (Anneli), Prokopenko, I. (Inga), Ricceri, F. (Fulvio), Santos, E. (Eugenio), Smit, J.H. (Johannes), Soranzo, N. (Nicole), Song, K. (Kijoung), Sovio, U. (Ulla), Stumvoll, M. (Michael), Surakk, I. (Ida), Thorgeirsson, T.E. (Thorgeir), Thorsteinsdottir, U. (Unnur), Troakes, C. (Claire), Tyrfingsson, T. (Thorarinn), Tönjes, A. (Anke), Uiterwaal, C.S.P.M. (Cuno), Uitterlinden, A.G. (André), Harst, P. (Pim) van der, Schouw, Y.T. (Yvonne) van der, Staehlin, O. (Oliver), Vogelzangs, N. (Nicole), Vollenweider, P. (Peter), Waeber, G. (Gérard), Wareham, N.J. (Nick), Waterworth, D. (Dawn), Whitfield, J.B. (John), Wichmann, E.H. (Erich), Willemsen, G.A.H.M. (Gonneke), Witteman, J.C.M. (Jacqueline), Yuan, X. (Xin), Zhai, G. (Guangju), Zhao, J.H. (Jing Hua), Zhang, W. (Weihua), Martin, N.G. (Nicholas), Metspalu, A. (Andres), Doering, A. (Angela), Scott, J. (James), Spector, T.D. (Timothy), Loos, R.J.F. (Ruth), Boomsma, D.I. (Dorret), Mooser, V. (Vincent), Peltonen, L. (Leena Johanna), Stefansson, K. (Kari), Tikka-Kleemola, P. (Päivi), Vineis, P. (Paolo), Sommer, W.H. (Wolfgang), Kooner, J.S. (Jaspal), Spanagel, R. (Rainer), Heberlein, U.A. (Ulrike), Järvelin, M.R., Elliott, P. (Paul), Aulchenko, Y.S. (Yurii), Bakker, S.J.L. (Stephan), Schumann, G. (Gunter), Coin, L. (Lachlan), Lourdusamy, A. (Anbarasu), Charoen, P. (Pimphen), Berger, K.H. (Karen), Stacey, D. (David), Desrivières, S. (Sylvane), Aliev, F.A. (Fazil), Khan, A.A. (Anokhi), Amin, N. (Najaf), Bakalkin, G. (Georgy), Balkau, B. (Beverley), Beulens, J.W.J. (Joline), Bilbao, A. (Ainhoa), Boer, R.A. (Rudolf) de, Beury, D. (Delphine), Bots, M.L. (Michiel), Breetvelt, E.J. (Elemi), Cauchi, S. (Stephane), Cavalcanti-Proença, C. (Christine), Chambers, J.C. (John), Clarke, T.-K., Dahmen, N. (N.), Geus, E.J.C. (Eco) de, Dick, D. (Danielle), Ducci, F. (Francesca), Easton, A. (Alanna), Edenberg, H.J. (Howard), Esk, T. (Tõnu), Fernández-Medarde, A. (Alberto), Foroud, T. (Tatiana), Freimer, N.B. (Nelson), Girault, J.-A., Grobbee, D.E. (Diederick), Guarrera, S. (Simonetta), Gudbjartsson, D.F. (Daniel), Hartikainen, A.L., Heath, A.C. (Andrew), Hesselbrock, V. (Victor), Hofman, A. (Albert), Hottenga, J.J. (Jouke Jan), Isohanni, M.K. (Matti), Kaprio, J. (Jaakko), Khaw, K-T. (Kay-Tee), Kuehnel, B. (Brigitte), Laitinen, J. (Jaana), Lobbens, S. (Stéphane), Luan, J., Mangino, M. (Massimo), Maroteaux, M. (Matthieu), Matullo, G. (Giuseppe), McCarthy, M.I. (Mark), Mueller, C. (Christian), Navis, G. (Gerjan), Numans, M.E. (Mattijs), Núñez, A.M. (Alejandro), Nyholt, D.R. (Dale), Onland-Moret, N.C. (Charlotte), Oostra, B.A. (Ben), O'Reilly, P.F. (Paul), Palkovits, M. (Miklos), Penninx, B.W.J.H. (Brenda), Polidoro, S. (Silvia), Pouta, A. (Anneli), Prokopenko, I. (Inga), Ricceri, F. (Fulvio), Santos, E. (Eugenio), Smit, J.H. (Johannes), Soranzo, N. (Nicole), Song, K. (Kijoung), Sovio, U. (Ulla), Stumvoll, M. (Michael), Surakk, I. (Ida), Thorgeirsson, T.E. (Thorgeir), Thorsteinsdottir, U. (Unnur), Troakes, C. (Claire), Tyrfingsson, T. (Thorarinn), Tönjes, A. (Anke), Uiterwaal, C.S.P.M. (Cuno), Uitterlinden, A.G. (André), Harst, P. (Pim) van der, Schouw, Y.T. (Yvonne) van der, Staehlin, O. (Oliver), Vogelzangs, N. (Nicole), Vollenweider, P. (Peter), Waeber, G. (Gérard), Wareham, N.J. (Nick), Waterworth, D. (Dawn), Whitfield, J.B. (John), Wichmann, E.H. (Erich), Willemsen, G.A.H.M. (Gonneke), Witteman, J.C.M. (Jacqueline), Yuan, X. (Xin), Zhai, G. (Guangju), Zhao, J.H. (Jing Hua), Zhang, W. (Weihua), Martin, N.G. (Nicholas), Metspalu, A. (Andres), Doering, A. (Angela), Scott, J. (James), Spector, T.D. (Timothy), Loos, R.J.F. (Ruth), Boomsma, D.I. (Dorret), Mooser, V. (Vincent), Peltonen, L. (Leena Johanna), Stefansson, K. (Kari), Tikka-Kleemola, P. (Päivi), Vineis, P. (Paolo), Sommer, W.H. (Wolfgang), Kooner, J.S. (Jaspal), Spanagel, R. (Rainer), Heberlein, U.A. (Ulrike), Järvelin, M.R., Elliott, P. (Paul), Aulchenko, Y.S. (Yurii), and Bakker, S.J.L. (Stephan)
- Abstract
Alcohol consumption is a moderately heritable trait, but the genetic basis in humans is largely unknown, despite its clinical and societal importance. We report a genome-wide association study meta-analysis of ∼2.5 million directly genotyped or imputed SNPs with alcohol consumption (gram per day per kilogram body weight) among 12 population-based samples of European ancestry, comprising 26,316 individuals, with replication genotyping in an additional 21,185 individuals. SNP rs6943555 in autism susceptibility candidate 2 gene (AUTS2) was associated with alcohol consumption at genome-wide significance (P = 4 x 10-8to P = 4 x 10-9). We found a genotype-specific expression of AUTS2 in 96 human prefrontal cortex samples (P = 0.026) and significant (P < 0.017) differences in expression of AUTS2 in whole-brain extracts of mice selected for differences in voluntary alcohol consumption. Downregulation of an AUTS2 homolog caused reduced alcohol sensitivity in Drosophila (P < 0.001). Our finding of a regulator of alcohol consumption adds knowledge to our understanding of genetic mech
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- 2011
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23. Genetic architecture of circulating lipid levels
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Demirkan, A. (Ayşe), Amin, N. (Najaf), Isaacs, A.J. (Aaron), Järvelin, M.R., Whitfield, J.B. (John), Wichmann, H.E. (Heinz Erich), Kyvik, K.O. (Kirsten Ohm), Rudan, I. (Igor), Gieger, C. (Christian), Hicks, A.A. (Andrew), Johansson, A. (Åsa), Hottenga, J.J. (Jouke Jan), Smith, J.J. (Johannes), Wild, S.H. (Sarah), Pedersen, N.L. (Nancy), Willemsen, G.A.H.M. (Gonneke), Mangino, M. (Massimo), Hayward, C. (Caroline), Uitterlinden, A.G. (André), Hofman, A. (Albert), Witteman, J.C.M. (Jacqueline), Montgomery, G.W. (Grant), Pietilainen, K.H. (Kirsi Hannele), Rantanen, T. (Taina), Kaprio, J. (Jaakko), Döring, A. (Angela), Pramstaller, P.P. (Peter Paul), Gyllensten, U. (Ulf), Geus, E.J.C. (Eco) de, Penninx, B.W.J.H. (Brenda), Wilson, J.F. (James), Rivadeneria, F. (Fernando), Magnusson, P.K. (Patrik), Boomsma, D.I. (Dorret), Spector, T.D. (Timothy), Campbell, H. (Harry), Hoehne, B. (Birgit), Martin, N.G. (Nicholas), Oostra, B.A. (Ben), McCarthy, M.I. (Mark), Peltonen-Palotie, L. (Leena), Aulchenko, Y.S. (Yurii), Visscher, P.M. (Peter), Ripatti, S. (Samuli), Janssens, A.C.J.W. (Cécile), Tikka-Kleemola, P. (Päivi), Demirkan, A. (Ayşe), Amin, N. (Najaf), Isaacs, A.J. (Aaron), Järvelin, M.R., Whitfield, J.B. (John), Wichmann, H.E. (Heinz Erich), Kyvik, K.O. (Kirsten Ohm), Rudan, I. (Igor), Gieger, C. (Christian), Hicks, A.A. (Andrew), Johansson, A. (Åsa), Hottenga, J.J. (Jouke Jan), Smith, J.J. (Johannes), Wild, S.H. (Sarah), Pedersen, N.L. (Nancy), Willemsen, G.A.H.M. (Gonneke), Mangino, M. (Massimo), Hayward, C. (Caroline), Uitterlinden, A.G. (André), Hofman, A. (Albert), Witteman, J.C.M. (Jacqueline), Montgomery, G.W. (Grant), Pietilainen, K.H. (Kirsi Hannele), Rantanen, T. (Taina), Kaprio, J. (Jaakko), Döring, A. (Angela), Pramstaller, P.P. (Peter Paul), Gyllensten, U. (Ulf), Geus, E.J.C. (Eco) de, Penninx, B.W.J.H. (Brenda), Wilson, J.F. (James), Rivadeneria, F. (Fernando), Magnusson, P.K. (Patrik), Boomsma, D.I. (Dorret), Spector, T.D. (Timothy), Campbell, H. (Harry), Hoehne, B. (Birgit), Martin, N.G. (Nicholas), Oostra, B.A. (Ben), McCarthy, M.I. (Mark), Peltonen-Palotie, L. (Leena), Aulchenko, Y.S. (Yurii), Visscher, P.M. (Peter), Ripatti, S. (Samuli), Janssens, A.C.J.W. (Cécile), and Tikka-Kleemola, P. (Päivi)
- Abstract
Serum concentrations of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs) and total cholesterol (TC) are important heritable risk factors for cardiovascular disease. Although genome-wide association studies (GWASs) of circulating lipid levels have identified numerous loci, a substantial portion of the heritability of these traits remains unexplained. Evidence of unexplained genetic variance can be detected by combining multiple independent markers into additive genetic risk scores. Such polygenic scores, constructed using results from the ENGAGE Consortium GWAS on serum lipids, were applied to predict lipid levels in an independent population-based study, the Rotterdam Study-II (RS-II). We additionally tested for evidence of a shared genetic basis for different lipid phenotypes. Finally, the polygenic score approach was used to identify an alternative genome-wide significance threshold before pathway analysis and those results were compared with those based on the classical genome-wide significance threshold. Our study provides evidence suggesting that many loci influencing circulating lipid levels remain undiscovered. Cross-prediction models suggested a small overlap between the polygenic backgrounds involved in determining LDL-C, HDL-C and TG levels. Pathway analysis utilizing the best polygenic score for TC uncovered extra information compared with using only genome-wide significant loci. These results suggest that the genetic architecture of circulating lipids involves a number of undiscovered variants with very small effects, and that increasing GWAS sample sizes will enable the identification of novel variants that regulate lipid levels.
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- 2011
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24. Physical activity attenuates the influence of FTO variants on obesity risk: A meta-analysis of 218,166 adults and 19,268 children
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Kilpeläinen, T.O. (Tuomas), Qi, L. (Lu), Brage, S. (Soren), Sharp, S.J. (Stephen), Sonestedt, E. (Emily), Demerath, E.W. (Ellen), Ahmad, T. (Tariq), Mora, S. (Samia), Kaakinen, M. (Marika), Sandholt, C. (Camilla), Holzapfel, C. (Christina), Autenrieth, C.S. (Christine), Hyppönen, E. (Elina), Cauchi, S. (Stephane), He, M. (Meian), Kutalik, Z. (Zoltán), Kumari, M. (Meena), Stancáková, A. (Alena), Meidtner, K. (Karina), Balkau, B. (Beverley), Tan, J.T. (Jonathan), Mangino, M. (Massimo), Timpson, N.J. (Nicholas), Song, Y. (Yiqing), Zillikens, M.C. (Carola), Jablonski, K.A. (Kathleen), Garcia, M. (Melissa), Johansson, S. (Stefan), Bragg-Gresham, J.L. (Jennifer L.), Wu, Y. (Ying), Vliet-Ostaptchouk, J.V. (Jana) van, Onland-Moret, N.C. (Charlotte), Zimmermann, E. (Esther), Rivera, N.V. (Natalia), Tanaka, T. (Toshiko), Stringham, H.M. (Heather), Silbernagel, G. (Günther), Kanoni, S. (Stavroula), Feitosa, M.F. (Mary Furlan), Snitker, S. (Soren), Ruiz, J.R. (Jonatan), Metter, J. (Jeffery), Larrad, M.T.M., Atalay, M. (Mustafa), Hakanen, M. (Maarit), Amin, N. (Najaf), Cavalcanti-Proença, C. (Christine), Grøntved, A. (Anders), Hallmans, G. (Göran), Jansson, J.O., Kuusisto, J. (Johanna), Kähönen, M. (Mika), Lutsey, P.L. (Pamela), Nolan, J.J. (John), Palla, L. (Luigi), Pedersen, O. (Oluf), Pérusse, L. (Louis), Renström, F. (Frida), Scott, R.A. (Robert), Shungin, D. (Dmitry), Sovio, U. (Ulla), Tammelin, T.H. (Tuija), Rönnemaa, T. (Tapani), Lakka, T.A. (Timo), Uusitupa, M. (Matti), Rios, M.S., Ferrucci, L. (Luigi), Bouchard, C. (Claude), Meirhaeghe, A. (Aline), Fu, M. (Mao), Walker, M. (Mark), Borecki, I.B. (Ingrid), Dedoussis, G.V. (George), Fritsche, A. (Andreas), Ohlsson, C. (Claes), Boehnke, M. (Michael), Bandinelli, S. (Stefania), Tikka-Kleemola, P. (Päivi), Lawlor, D.A. (Debbie), Gudnason, V. (Vilmundur), Harris, T.B. (Tamara), Sørensen, T.I.A. (Thorkild), Mohlke, K.L. (Karen), Hofman, A. (Albert), Uitterlinden, A.G. (André), Tuomilehto, J. (Jaakko), Lehtimäki, T. (Terho), Raitakari, O. (Olli), Isomaa, B. (Bo), Njolstad, P. (Pal), Florez, J.C. (Jose), Liu, S. (Simin), Ness, A.R. (Andrew), Spector, T.D. (Timothy), Tai, E.S. (Shyong), Froguel, P. (Philippe), Boeing, H. (Heiner), Laakso, M. (Markku), Marmot, M. (Michael), Bergmann, S.M. (Sven), Power, C. (Chris), Khaw, K.-T., Chasman, D.I. (Daniel), Ridker, P.M. (Paul), Hansen, T. (Torben), Monda, K.L. (Keri), Illig, T. (Thomas), Järvelin, M.R., Wareham, N.J. (Nick), Ebrahim, S. (Shanil), Hu, F.B. (Frank), Groop, L. (Leif), Orho-Melander, M. (Marju), Ekelund, U. (Ulf), Franks, P.W. (Paul), Loos, R.J.F. (Ruth), Kilpeläinen, T.O. (Tuomas), Qi, L. (Lu), Brage, S. (Soren), Sharp, S.J. (Stephen), Sonestedt, E. (Emily), Demerath, E.W. (Ellen), Ahmad, T. (Tariq), Mora, S. (Samia), Kaakinen, M. (Marika), Sandholt, C. (Camilla), Holzapfel, C. (Christina), Autenrieth, C.S. (Christine), Hyppönen, E. (Elina), Cauchi, S. (Stephane), He, M. (Meian), Kutalik, Z. (Zoltán), Kumari, M. (Meena), Stancáková, A. (Alena), Meidtner, K. (Karina), Balkau, B. (Beverley), Tan, J.T. (Jonathan), Mangino, M. (Massimo), Timpson, N.J. (Nicholas), Song, Y. (Yiqing), Zillikens, M.C. (Carola), Jablonski, K.A. (Kathleen), Garcia, M. (Melissa), Johansson, S. (Stefan), Bragg-Gresham, J.L. (Jennifer L.), Wu, Y. (Ying), Vliet-Ostaptchouk, J.V. (Jana) van, Onland-Moret, N.C. (Charlotte), Zimmermann, E. (Esther), Rivera, N.V. (Natalia), Tanaka, T. (Toshiko), Stringham, H.M. (Heather), Silbernagel, G. (Günther), Kanoni, S. (Stavroula), Feitosa, M.F. (Mary Furlan), Snitker, S. (Soren), Ruiz, J.R. (Jonatan), Metter, J. (Jeffery), Larrad, M.T.M., Atalay, M. (Mustafa), Hakanen, M. (Maarit), Amin, N. (Najaf), Cavalcanti-Proença, C. (Christine), Grøntved, A. (Anders), Hallmans, G. (Göran), Jansson, J.O., Kuusisto, J. (Johanna), Kähönen, M. (Mika), Lutsey, P.L. (Pamela), Nolan, J.J. (John), Palla, L. (Luigi), Pedersen, O. (Oluf), Pérusse, L. (Louis), Renström, F. (Frida), Scott, R.A. (Robert), Shungin, D. (Dmitry), Sovio, U. (Ulla), Tammelin, T.H. (Tuija), Rönnemaa, T. (Tapani), Lakka, T.A. (Timo), Uusitupa, M. (Matti), Rios, M.S., Ferrucci, L. (Luigi), Bouchard, C. (Claude), Meirhaeghe, A. (Aline), Fu, M. (Mao), Walker, M. (Mark), Borecki, I.B. (Ingrid), Dedoussis, G.V. (George), Fritsche, A. (Andreas), Ohlsson, C. (Claes), Boehnke, M. (Michael), Bandinelli, S. (Stefania), Tikka-Kleemola, P. (Päivi), Lawlor, D.A. (Debbie), Gudnason, V. (Vilmundur), Harris, T.B. (Tamara), Sørensen, T.I.A. (Thorkild), Mohlke, K.L. (Karen), Hofman, A. (Albert), Uitterlinden, A.G. (André), Tuomilehto, J. (Jaakko), Lehtimäki, T. (Terho), Raitakari, O. (Olli), Isomaa, B. (Bo), Njolstad, P. (Pal), Florez, J.C. (Jose), Liu, S. (Simin), Ness, A.R. (Andrew), Spector, T.D. (Timothy), Tai, E.S. (Shyong), Froguel, P. (Philippe), Boeing, H. (Heiner), Laakso, M. (Markku), Marmot, M. (Michael), Bergmann, S.M. (Sven), Power, C. (Chris), Khaw, K.-T., Chasman, D.I. (Daniel), Ridker, P.M. (Paul), Hansen, T. (Torben), Monda, K.L. (Keri), Illig, T. (Thomas), Järvelin, M.R., Wareham, N.J. (Nick), Ebrahim, S. (Shanil), Hu, F.B. (Frank), Groop, L. (Leif), Orho-Melander, M. (Marju), Ekelund, U. (Ulf), Franks, P.W. (Paul), and Loos, R.J.F. (Ruth)
- Abstract
Background: The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n = 218,166) and nine studies of children and adolescents (n = 19,268). Methods and Findings: All studies identified to have data on the FTO rs9939609 variant (or any proxy [r2>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTO×PA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A-) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20-1.26), but PA attenuated this effect (pinteraction= 0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio = 1.22/allele, 95% CI 1.19-1.25) than in the inactive group (odds ratio = 1.30/allele, 95% CI 1.24-1.36). No such interaction was found in children and adolescents. Conclu
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- 2011
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25. Runs of homozygosity do not influence survival to old age
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Kuningas, M. (Maris), McQuillan, R. (Ruth), Wilson, J.F. (James), Hofman, A. (Albert), Tikka-Kleemola, P. (Päivi), Uitterlinden, A.G. (André), Tiemeier, H.W. (Henning), Kuningas, M. (Maris), McQuillan, R. (Ruth), Wilson, J.F. (James), Hofman, A. (Albert), Tikka-Kleemola, P. (Päivi), Uitterlinden, A.G. (André), and Tiemeier, H.W. (Henning)
- Abstract
Runs of homozygosity (ROH) are extended tracts of adjacent homozygous single nucleotide polymorphisms (SNPs) that are more common in unrelated individuals than previously thought. It has been proposed that estimating ROH on a genome-wide level, by making use of the genome-wide single nucleotide polymorphism (SNP) data, will enable to indentify recessive variants underlying complex traits. Here, we examined ROH larger than 1.5 Mb individually and in combination for association with survival in 5974 participants of the Rotterdam Study. In addition, we assessed the role of overall homozygosity, expressed as a percentage of the autosomal genome that is in ROH longer than 1.5 Mb, on survival during a mean follow-up period of 12 years. None of these measures of homozygosity was associated with survival to old age.
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- 2011
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26. Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile
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Kilpeläinen, T.O. (Tuomas), Zillikens, M.C. (Carola), Stancáková, A. (Alena), Finucane, F.M. (Francis), Ried, J.S. (Janina), Langenberg, C. (Claudia), Zhang, W. (Weihua), Beckmann, J.S. (Jacques), Luan, J., Vandenput, L. (Liesbeth), Styrkarsdottir, U. (Unnur), Zhou, Y. (Yanhua), Smith, A.V. (Albert Vernon), Zhao, J.H. (Jing Hua), Amin, N. (Najaf), Vedantam, S. (Sailaja), Shin, S.-Y., Haritunians, T. (Talin), Fu, M. (Mao), Feitosa, M.F. (Mary Furlan), Kumari, M. (Meena), Halldorsson, B.V. (Bjarni), Tikkanen, E. (Emmi), Mangino, M. (Massimo), Hayward, C. (Caroline), Song, C. (Ci), Arnold, A.M. (Alice), Oostra, B.A. (Ben), Campbell, H. (Harry), Cupples, L.A. (Adrienne), Davis, K.E. (Kathryn), Döring, A. (Angela), Eiriksdottir, G. (Gudny), Estrada Gil, K. (Karol), Fernández-Real, J.M., Garcia, M. (Melissa), Gieger, C. (Christian), Glazer, N.L. (Nicole), Guiducci, C. (Candace), Hofman, A. (Albert), Humphries, S.E. (Steve), Isomaa, B. (Bo), Jacobs, L.C. (Leonie), Jula, A. (Antti), Karasik, D. (David), Karlsson, M.K. (Magnus), Khaw, K-T. (Kay-Tee), Kim, L.J. (Lauren), Kivimaki, M. (Mika), Klopp, N. (Norman), Kuhnel, B. (Brigitte), Kuusisto, J. (Johanna), Liu, Y. (YongMei), Ljunggren, Ö., Lorentzon, M. (Mattias), Luben, R.N. (Robert), McKnight, B. (Barbara), Mellström, D. (Dan), Mitchell, B.D. (Braxton), Mooser, V. (Vincent), Moreno, J.M., Männistö, S. (Satu), O'Connell, J.R. (Jeffery), Pascoe, L. (Laura), Peltonen, L. (Leena Johanna), Peral, B. (Belén), Perola, M. (Markus), Psaty, B.M. (Bruce), Salomaa, V. (Veikko), Savage, D.B. (David), Semple, R.K. (Robert), Skaric-Juric, T. (Tatjana), Sigurdsson, G. (Gunnar), Spector, T.D. (Timothy), Syvänen, A.-C., Talmud, P.J. (Philippa), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Uitterlinden, A.G. (André), Tikka-Kleemola, P. (Päivi), Vidal-Puig, A. (Antonio), Wild, S.H. (Sarah), Wright, A.F. (Alan), Clegg, D.J. (Deborah), Schadt, E.E. (Eric), Wilson, J.F. (James), Rudan, I. (Igor), Ripatti, S. (Samuli), Borecki, I.B. (Ingrid), Shuldiner, A.R. (Alan), Ingelsson, E. (Erik), Jansson, J.O., Kaplan, R.C. (Robert), Gudnason, V. (Vilmundur), Harris, T.B. (Tamara), Groop, L. (Leif), Kiel, D.P. (Douglas), Rivadeneira Ramirez, F. (Fernando), Walker, M. (Mark), Barroso, I.E. (Inês), Vollenweider, P. (Peter), Waeber, G. (Gérard), Chambers, J.C. (John), Kooner, J.S. (Jaspal), Soranzo, N. (Nicole), Hirschhorn, J.N. (Joel), Stefansson, K. (Kari), Wichmann, H.E. (Heinz Erich), Ohlsson, C. (Claes), O'Rahilly, S. (Stephen), Wareham, N.J. (Nick), Speliotes, E.K. (Elizabeth), Fox, C.S. (Caroline), Laakso, M. (Markku), Loos, R.J.F. (Ruth), Aulchenko, Y.S. (Yurii), Kilpeläinen, T.O. (Tuomas), Zillikens, M.C. (Carola), Stancáková, A. (Alena), Finucane, F.M. (Francis), Ried, J.S. (Janina), Langenberg, C. (Claudia), Zhang, W. (Weihua), Beckmann, J.S. (Jacques), Luan, J., Vandenput, L. (Liesbeth), Styrkarsdottir, U. (Unnur), Zhou, Y. (Yanhua), Smith, A.V. (Albert Vernon), Zhao, J.H. (Jing Hua), Amin, N. (Najaf), Vedantam, S. (Sailaja), Shin, S.-Y., Haritunians, T. (Talin), Fu, M. (Mao), Feitosa, M.F. (Mary Furlan), Kumari, M. (Meena), Halldorsson, B.V. (Bjarni), Tikkanen, E. (Emmi), Mangino, M. (Massimo), Hayward, C. (Caroline), Song, C. (Ci), Arnold, A.M. (Alice), Oostra, B.A. (Ben), Campbell, H. (Harry), Cupples, L.A. (Adrienne), Davis, K.E. (Kathryn), Döring, A. (Angela), Eiriksdottir, G. (Gudny), Estrada Gil, K. (Karol), Fernández-Real, J.M., Garcia, M. (Melissa), Gieger, C. (Christian), Glazer, N.L. (Nicole), Guiducci, C. (Candace), Hofman, A. (Albert), Humphries, S.E. (Steve), Isomaa, B. (Bo), Jacobs, L.C. (Leonie), Jula, A. (Antti), Karasik, D. (David), Karlsson, M.K. (Magnus), Khaw, K-T. (Kay-Tee), Kim, L.J. (Lauren), Kivimaki, M. (Mika), Klopp, N. (Norman), Kuhnel, B. (Brigitte), Kuusisto, J. (Johanna), Liu, Y. (YongMei), Ljunggren, Ö., Lorentzon, M. (Mattias), Luben, R.N. (Robert), McKnight, B. (Barbara), Mellström, D. (Dan), Mitchell, B.D. (Braxton), Mooser, V. (Vincent), Moreno, J.M., Männistö, S. (Satu), O'Connell, J.R. (Jeffery), Pascoe, L. (Laura), Peltonen, L. (Leena Johanna), Peral, B. (Belén), Perola, M. (Markus), Psaty, B.M. (Bruce), Salomaa, V. (Veikko), Savage, D.B. (David), Semple, R.K. (Robert), Skaric-Juric, T. (Tatjana), Sigurdsson, G. (Gunnar), Spector, T.D. (Timothy), Syvänen, A.-C., Talmud, P.J. (Philippa), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Uitterlinden, A.G. (André), Tikka-Kleemola, P. (Päivi), Vidal-Puig, A. (Antonio), Wild, S.H. (Sarah), Wright, A.F. (Alan), Clegg, D.J. (Deborah), Schadt, E.E. (Eric), Wilson, J.F. (James), Rudan, I. (Igor), Ripatti, S. (Samuli), Borecki, I.B. (Ingrid), Shuldiner, A.R. (Alan), Ingelsson, E. (Erik), Jansson, J.O., Kaplan, R.C. (Robert), Gudnason, V. (Vilmundur), Harris, T.B. (Tamara), Groop, L. (Leif), Kiel, D.P. (Douglas), Rivadeneira Ramirez, F. (Fernando), Walker, M. (Mark), Barroso, I.E. (Inês), Vollenweider, P. (Peter), Waeber, G. (Gérard), Chambers, J.C. (John), Kooner, J.S. (Jaspal), Soranzo, N. (Nicole), Hirschhorn, J.N. (Joel), Stefansson, K. (Kari), Wichmann, H.E. (Heinz Erich), Ohlsson, C. (Claes), O'Rahilly, S. (Stephen), Wareham, N.J. (Nick), Speliotes, E.K. (Elizabeth), Fox, C.S. (Caroline), Laakso, M. (Markku), Loos, R.J.F. (Ruth), and Aulchenko, Y.S. (Yurii)
- Abstract
Genome-wide association studies have identified 32 loci influencing body mass index, but this measure does not distinguish lean from fat mass. To identify adiposity loci, we meta-analyzed associations between ∼2.5 million SNPs and body fat percentage from 36,626 individuals and followed up the 14 most significant (P < 10-6) independent loci in 39,576 individuals. We confirmed a previously established adiposity locus in FTO (P = 3 × 10-26) and identified two new loci associated with body fat percentage, one near IRS1 (P = 4 × 10-11) and one near SPRY2 (P = 3 × 10-8). Both loci contain genes with potential links to adipocyte physiology. Notably, the body-fat-decreasing allele near IRS1 is associated with decreased IRS1 expression and with an impaired metabolic profile, including an increased visceral to subcutaneous fat ratio, insulin resistance, dyslipidemia, risk of diabetes and coronary artery disease and decreased adiponectin levels. Our findings provide new insights into adiposity and insulin resistance.
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- 2011
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27. Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight
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Freathy, R.M. (Rachel), Mook-Kanamori, D.O. (Dennis), Sovio, U. (Ulla), Prokopenko, I. (Inga), Timpson, N.J. (Nicholas), Berry, D. (Diane), Warrington, N.M. (Nicole), Widen, E. (Elisabeth), Hottenga, J.J. (Jouke Jan), Kaakinen, M. (Marika), Lange, L.A. (Leslie), Bradfield, J.P. (Jonathan), Kerkhof, M. (Marjan), Marsh, J.A. (Julie), Mägi, R. (Reedik), Chen, C. (Chao), Lyon, H.N. (Helen), Kirin, M. (Mirna), Adair, L.S. (Linda), Aulchenko, Y.S. (Yurii), Bennett, A.J. (Amanda), Borja, J.B. (Judith), Bouatia-Naji, N. (Nabila), Charoen, P. (Pimphen), Coin, L. (Lachlan), Cousminer, D.L. (Diana), Geus, E.J.C. (Eco) de, Deloukas, P. (Panagiotis), Elliott, P. (Paul), Evans, D.M. (David), Froguel, P. (Philippe), Glaser, B. (Beate), Groves, C.J. (Christopher), Hartikainen, A.L., Hassanali, N. (Neelam), Hirschhorn, J.N. (Joel), Hofman, A. (Albert), Holly, J.M.P. (Jeff), Hyppönen, E. (Elina), Kanoni, S. (Stavroula), Knight, B.A. (Bridget), Laitinen, J. (Jaana), Lindgren, C.M. (Cecilia), McArdle, W.L. (Wendy), O'Reilly, P.F. (Paul), Pennell, C.E. (Craig), Postma, D.S. (Dirkje), Pouta, A. (Anneli), Ramasamy, A. (Adaikalavan), Rayner, N.W. (Nigel William), Ring, S.M. (Susan), Rivadeneira Ramirez, F. (Fernando), Shields, B.M. (Beverley), Strachan, D.P. (David), Surakka, I. (Ida), Taanila, A. (Anja), Tiesler, C. (Carla), Uitterlinden, A.G. (André), Tikka-Kleemola, P. (Päivi), Wijga, A.H. (Alet), Willemsen, G.A.H.M. (Gonneke), Zhang, H. (Haitao), Zhao, J.H. (Jing Hua), Wilson, J.F. (James), Steegers-Theunissen, R.P.M. (Régine), Hattersley, A.T. (Andrew), Hagen, K. (Knut), Peltonen, L. (Leena Johanna), Mohlke, K.L. (Karen), Grant, S.F.A. (Struan), Hakonarson, H. (Hakon), Koppelman, G.H. (Gerard), Dedoussis, G.V. (George), Heinrich, J. (Joachim), Gillman, M.W. (Matthew W.), Palmer, C. (Cameron), Frayling, T.M. (Timothy), Boomsma, D.I. (Dorret), Smith, A.V. (Davey), Power, C. (Christopher), Jaddoe, V.W.V. (Vincent), Jarvelin, M.-R. (Marjo-Riitta), McCarthy, M.I. (Mark), Freathy, R.M. (Rachel), Mook-Kanamori, D.O. (Dennis), Sovio, U. (Ulla), Prokopenko, I. (Inga), Timpson, N.J. (Nicholas), Berry, D. (Diane), Warrington, N.M. (Nicole), Widen, E. (Elisabeth), Hottenga, J.J. (Jouke Jan), Kaakinen, M. (Marika), Lange, L.A. (Leslie), Bradfield, J.P. (Jonathan), Kerkhof, M. (Marjan), Marsh, J.A. (Julie), Mägi, R. (Reedik), Chen, C. (Chao), Lyon, H.N. (Helen), Kirin, M. (Mirna), Adair, L.S. (Linda), Aulchenko, Y.S. (Yurii), Bennett, A.J. (Amanda), Borja, J.B. (Judith), Bouatia-Naji, N. (Nabila), Charoen, P. (Pimphen), Coin, L. (Lachlan), Cousminer, D.L. (Diana), Geus, E.J.C. (Eco) de, Deloukas, P. (Panagiotis), Elliott, P. (Paul), Evans, D.M. (David), Froguel, P. (Philippe), Glaser, B. (Beate), Groves, C.J. (Christopher), Hartikainen, A.L., Hassanali, N. (Neelam), Hirschhorn, J.N. (Joel), Hofman, A. (Albert), Holly, J.M.P. (Jeff), Hyppönen, E. (Elina), Kanoni, S. (Stavroula), Knight, B.A. (Bridget), Laitinen, J. (Jaana), Lindgren, C.M. (Cecilia), McArdle, W.L. (Wendy), O'Reilly, P.F. (Paul), Pennell, C.E. (Craig), Postma, D.S. (Dirkje), Pouta, A. (Anneli), Ramasamy, A. (Adaikalavan), Rayner, N.W. (Nigel William), Ring, S.M. (Susan), Rivadeneira Ramirez, F. (Fernando), Shields, B.M. (Beverley), Strachan, D.P. (David), Surakka, I. (Ida), Taanila, A. (Anja), Tiesler, C. (Carla), Uitterlinden, A.G. (André), Tikka-Kleemola, P. (Päivi), Wijga, A.H. (Alet), Willemsen, G.A.H.M. (Gonneke), Zhang, H. (Haitao), Zhao, J.H. (Jing Hua), Wilson, J.F. (James), Steegers-Theunissen, R.P.M. (Régine), Hattersley, A.T. (Andrew), Hagen, K. (Knut), Peltonen, L. (Leena Johanna), Mohlke, K.L. (Karen), Grant, S.F.A. (Struan), Hakonarson, H. (Hakon), Koppelman, G.H. (Gerard), Dedoussis, G.V. (George), Heinrich, J. (Joachim), Gillman, M.W. (Matthew W.), Palmer, C. (Cameron), Frayling, T.M. (Timothy), Boomsma, D.I. (Dorret), Smith, A.V. (Davey), Power, C. (Christopher), Jaddoe, V.W.V. (Vincent), Jarvelin, M.-R. (Marjo-Riitta), and McCarthy, M.I. (Mark)
- Abstract
To identify genetic variants associated with birth weight, we meta-analyzed six genome-wide association (GWA) studies (n = 10,623 Europeans from pregnancy/birt
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- 2010
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28. Insulin VNTR and IGF-1 promoter region polymorphisms are not associated with body composition in early childhood: The generation R study
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Maas, J.A.J.B.M. (Janneke), Mook-Kanamori, D.O. (Dennis), Ay, L. (Lamise), Steegers-Theunissen, R.P.M. (Régine), Tikka-Kleemola, P. (Päivi), Hofman, A. (Albert), Hokken-Koelega, A.C.S. (Anita), Jaddoe, V.W.V. (Vincent), Maas, J.A.J.B.M. (Janneke), Mook-Kanamori, D.O. (Dennis), Ay, L. (Lamise), Steegers-Theunissen, R.P.M. (Régine), Tikka-Kleemola, P. (Päivi), Hofman, A. (Albert), Hokken-Koelega, A.C.S. (Anita), and Jaddoe, V.W.V. (Vincent)
- Abstract
Objective: The objective of this study was to examine the associations between insulin gene variable number of tandem repeats (INS VNTR) and insulin-like growth factor 1 (IGF1) gene promoter region polymorphisms with body composition in early childhood. Methods: This study was embedded in an ongoing prospective cohort study. Growth in early childhood (body mass index, total subcutaneous fat mass and waist-hip ratio) was assessed at birth and at the ages of 6 weeks and 24 months. DNA for genotyping was available in 738 children. Results: The genotype distribution of the INS VNTR gene was I/I 50.4%, I/III 40.4%, and III/III 9.2%. IGF1 genotypes were categorized in the following categories based on their 192-bp allele: homozygous (wild-type) 43.1%, heterozygous 45.8%, and noncarrier 11.2%. No differences were found in body mass index, total subcutaneous fat mass and waist-hip ratio in early childhood between the three groups for both the INS VNTR and IGF1 genotypes. We also did not find interactions between these genotypes and gender or birth weight on the effects of body composition measures. Conclusions: Our results do not support previous studies showing associations between INS VNTR and IGF1 promoter region polymorphisms with body composition in early childhood. Copyright
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- 2010
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29. Linkage and genome-wide association analysis of obesity-related phenotypes: Association of weight with the MGAT1 gene
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Johansson, A. (Åsa), Marroni, F. (Fabio), Hayward, C. (Caroline), Franklin, C.S. (Christopher), Kirichenko, A.V. (Anatoly), Jonasson, I. (Inger), Hicks, A.A. (Andrew), Vitart, V. (Veronique), Isaacs, A.J. (Aaron), Axenovich, T.I. (Tatiana), Campbell, S. (Susan), Floyd, J. (Jamie), Hastie, N. (Nick), Knott, S. (Sara), Lauc, G. (Gordan), Pichler, I. (Irene), Rotim, K. (Kresimir), Wild, S.H. (Sarah), Zorkoltseva, I.V. (Irina), Wilson, J.F. (James), Rudan, I. (Igor), Pattaro, C. (Cristian), Pramstaller, P.P. (Peter Paul), Oostra, B.A. (Ben), Wright, A.F. (Alan), Tikka-Kleemola, P. (Päivi), Aulchenko, Y.S. (Yurii), Gyllensten, U. (Ulf), Johansson, A. (Åsa), Marroni, F. (Fabio), Hayward, C. (Caroline), Franklin, C.S. (Christopher), Kirichenko, A.V. (Anatoly), Jonasson, I. (Inger), Hicks, A.A. (Andrew), Vitart, V. (Veronique), Isaacs, A.J. (Aaron), Axenovich, T.I. (Tatiana), Campbell, S. (Susan), Floyd, J. (Jamie), Hastie, N. (Nick), Knott, S. (Sara), Lauc, G. (Gordan), Pichler, I. (Irene), Rotim, K. (Kresimir), Wild, S.H. (Sarah), Zorkoltseva, I.V. (Irina), Wilson, J.F. (James), Rudan, I. (Igor), Pattaro, C. (Cristian), Pramstaller, P.P. (Peter Paul), Oostra, B.A. (Ben), Wright, A.F. (Alan), Tikka-Kleemola, P. (Päivi), Aulchenko, Y.S. (Yurii), and Gyllensten, U. (Ulf)
- Abstract
As major risk-factors for diabetes and cardiovascular diseases, the genetic contribution to obesity-related traits has been of interest for decades. Recently, a limited number of common genetic variants, which have replicated in different populations, have been identified. One approach to increase the statistical power in genetic mapping studies is to focus on populations with increased levels of linkage disequilibrium (LD) and reduced genetic diversity. We have performed joint linkage and genome-wide association analyses for weight and BMI in 3,448 (linkage) and 3,925 (association) partly overlapping healthy individuals from five European populations. A total of four chromosomal regions (two for weight and two for BMI) showed suggestive linkage (lod >2.69) either in one of the populations or in the joint data. At the genome-wide level (nominal P <1.6 × 10 7, Bonferroni-adjusted P 0.05) one single-nucleotide polymorphism (SNP) (rs12517906) (nominal P = 7.3 × 10-8) was associated with weight, whereas none with BMI. The SNP associated with weight is located close to MGAT1. The monoacylglycerol acyltransferase (MGAT) enzyme family is known to be involved in dietary fat absorption. There was no overlap between the linkage regions and the associated SNPs. Our results show that genetic effects influencing weight and BMI are shared across diverse European populations, even though some of these populations have experienced recent population bottlenecks and/or been affected by genetic drift. The analysis enabled us to identify a new candidate gene, MGAT1, associated with weight in women.
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- 2010
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30. Genes predict village of origin in rural Europe
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O'Dushlaine, C. (Colm), McQuillan, R. (Ruth), Weale, M.E. (Michael), Crouch, D.J.M. (Daniel), Johansson, A. (Åsa), Aulchenko, Y.S. (Yurii), Franklin, C.S. (Christopher), Polasek, O. (Ozren), Fuchsberger, C. (Christian), Corvin, A. (Aiden), Hicks, A.A. (Andrew), Vitart, V. (Veronique), Hayward, C. (Caroline), Wild, S.H. (Sarah), Meitinger, T. (Thomas), Tikka-Kleemola, P. (Päivi), Gyllensten, U. (Ulf), Wright, A.F. (Alan), Campbell, H. (Harry), Pramstaller, P.P. (Peter Paul), Rudan, I. (Igor), Wilson, J.F. (James), O'Dushlaine, C. (Colm), McQuillan, R. (Ruth), Weale, M.E. (Michael), Crouch, D.J.M. (Daniel), Johansson, A. (Åsa), Aulchenko, Y.S. (Yurii), Franklin, C.S. (Christopher), Polasek, O. (Ozren), Fuchsberger, C. (Christian), Corvin, A. (Aiden), Hicks, A.A. (Andrew), Vitart, V. (Veronique), Hayward, C. (Caroline), Wild, S.H. (Sarah), Meitinger, T. (Thomas), Tikka-Kleemola, P. (Päivi), Gyllensten, U. (Ulf), Wright, A.F. (Alan), Campbell, H. (Harry), Pramstaller, P.P. (Peter Paul), Rudan, I. (Igor), and Wilson, J.F. (James)
- Abstract
The genetic structure of human populations is important in population genetics, forensics and medicine. Using genome-wide scans and individuals with all four grandparents born in the same settlement, we here demonstrate remarkable geographical structure across 8-30 km in three different parts of rural Europe. After excluding close kin and inbreeding, village of origin could still be predicted correctly on the basis of genetic data for 89-100% of individuals.
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- 2010
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31. ProbABEL package for genome-wide association analysis of imputed data
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Aulchenko, Y.S. (Yurii), Struchalin, M.V. (Maksim), Tikka-Kleemola, P. (Päivi), Aulchenko, Y.S. (Yurii), Struchalin, M.V. (Maksim), and Tikka-Kleemola, P. (Päivi)
- Abstract
Background: Over the last few years, genome-wide association (GWA) studies became a tool of choice for the identification of loci associated with complex traits. Currently, imputed single nucleotide polymorphisms (SNP) data are frequently used in GWA analyzes. Correct analysis of imputed data calls for the implementation of specific methods which take genotype imputation uncertainty into account.Results: We developed the ProbABEL software package for the analysis of genome-wide imputed SNP data and quantitative, binary, and time-till-event outcomes under linear, logistic, and Cox proportional hazards models, respectively. For quantitative traits, the package also implements a fast two-step mixed model-based score test for association in samples with differential relationships, facilitating analysis in family-based studies, studies performed in human genetically isolated populations and outbred animal populations.Conclusions: ProbABEL package provides fast efficient way to analyze imputed data in genome-wide context and will facilitate future identification of complex trait loci.
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- 2010
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32. An epidemiological perspective on the future of direct-to-consumer personal genome testing
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Janssens, A.C.J.W. (Cécile), Tikka-Kleemola, P. (Päivi), Janssens, A.C.J.W. (Cécile), and Tikka-Kleemola, P. (Päivi)
- Abstract
Personal genome testing is offered via the internet directly to consumers. Most tests that are currently offered use data from genome-wide scans to predict risks for multiple common diseases and traits. The utility of these tests is limited, predominantly because they lack predictive ability and clear benefits for disease prevention that are specific for genetic risk groups. In the near future, personal genome tests will likely be based on whole genome sequencing, but will these technological advances increase the utility of personal genome testing? Whole genome sequencing theoretically provides information about the risks of both monogenic and complex diseases, but the practical utility remains to be demonstrated. The utility of testing depends on the predictive ability of the test, the likelihood of actionable test results, and the options available for the reduction of risks. For monogenic diseases, the likelihood of known mutations will be extremely low in the general population and it will be a challenge to recognize new causal variants among all rare variants that are found using sequencing. For complex diseases, the predictive ability of genetic tests will be mainly restricted by the heritability of the disease, but also by the genetic complexity of the disease etiology, which determines the extent to which the heritability can be understood. Given that numerous genetic and non-genetic risk factors interact in the causation of complex diseases, the predictive ability of genetic models will likely remain modest. Personal genome testing will have minimal benefits for individual consumers unless major breakthroughs are made in the near future.
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- 2010
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33. Genetic architecture of plasma adiponectin overlaps with the genetics of metabolic syndrome-related traits
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Henneman, P. (Peter), Aulchenko, Y.S. (Yurii), Frants, R.R. (Rune), Zorkoltseva, I.V. (Irina), Zillikens, M.C. (Carola), Frölich, M. (Marijke), Oostra, B.A. (Ben), Willems van Dijk, J.A.P. (Ko), Tikka-Kleemola, P. (Päivi), Henneman, P. (Peter), Aulchenko, Y.S. (Yurii), Frants, R.R. (Rune), Zorkoltseva, I.V. (Irina), Zillikens, M.C. (Carola), Frölich, M. (Marijke), Oostra, B.A. (Ben), Willems van Dijk, J.A.P. (Ko), and Tikka-Kleemola, P. (Päivi)
- Abstract
OBJECTIVE - Adiponectin, a hormone secreted by adipose tissue, is of particular interest in metabolic syndrome, because it is inversely correlated with obesity and insulin sensitivity. However, it is not known to what extent the genetics of plasma adiponectin and the genetics of obesity and insulin sensitivity are interrelated. We aimed to evaluate the heritability of plasma adiponectin and its genetic correlation with the metabolic syndrome and metabolic syndrome-related traits and the association between these traits and 10 ADIPOQ single nucleotide polymorphisms (SNPs). RESEARCH DESIGN AND METHODS - We made use of a family-based population, the Erasmus Rucphen Family study (1,258 women and 967 men). Heritability analysis was performed using a polygenic model. Genetic correlations were estimated using bivariate heritability analyses. Genetic association analysis was performed using a mixed model. RESULTS - Plasma adiponectin showed a heritability of 55.1%. Genetic correlations between plasma adiponectin HDL cholesterol and plasma insulin ranged from 15 to 24% but were not significant for fasting glucose, triglycerides, blood pressure, homeostasis model assessment of insulin resistance (HOMA-IR), and C-reactive protein. A significant association with plasma adiponectin was found for ADIPOQ variants rs17300539 and rs182052. A nominally significant association was found with plasma insulin and HOMA-IR and ADIPOQ variant rs17300539 after adjustment for plasma adiponectin. CONCLUSIONS - The significant genetic correlation between plasma adiponectin and HDL cholesterol and plasma insulin should be taken into account in the interpretation of genome-wide association studies. Association of ADIPOQ SNPs with plasma adiponectin was replicated, and we showed association between one ADIPOQ SNP and plasma insulin and HOMA-IR.
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- 2010
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34. Clear detection of ADIPOQ locus as the major gene for plasma adiponectin: Results of genome-wide association analyses including 4659 European individuals
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Heid, I.M. (Iris), Henneman, P. (Peter), Hicks, A.A. (Andrew), Coassin, S. (Stefan), Winkler, T.W. (Thomas), Aulchenko, Y.S. (Yurii), Fuchsberger, C. (Christian), Song, K. (Kijoung), Hivert, M.-F. (Marie-France), Waterworth, D. (Dawn), Timpson, N.J. (Nicholas), Richards, J.B. (Brent), Perry, J.R.B. (John), Tanaka, T. (Toshiko), Amin, N. (Najaf), Kollerits, B. (Barbara), Pichler, I. (Irene), Oostra, B.A. (Ben), Thorand, B. (Barbara), Frants, R.R. (Rune), Illig, T. (Thomas), Dupuis, J. (Josée), Glaser, B. (Beate), Spector, T.D. (Timothy), Guralnik, J.M. (Jack), Egan, J.M. (Josephine), Florez, J.C. (Jose), Evans, D.M. (David), Soranzo, N. (Nicole), Bandinelli, S. (Stefania), Carlson, O.D. (Olga), Frayling, T.M. (Timothy), Burling, K.A. (Keith), Smith, A.V. (Davey), Mooser, V. (Vincent), Ferrucci, L. (Luigi), Meigs, J.B. (James), Vollenweider, P. (Peter), Dijk, K.W.v., Pramstaller, P.P. (Peter Paul), Kronenberg, F. (Florian), Tikka-Kleemola, P. (Päivi), Heid, I.M. (Iris), Henneman, P. (Peter), Hicks, A.A. (Andrew), Coassin, S. (Stefan), Winkler, T.W. (Thomas), Aulchenko, Y.S. (Yurii), Fuchsberger, C. (Christian), Song, K. (Kijoung), Hivert, M.-F. (Marie-France), Waterworth, D. (Dawn), Timpson, N.J. (Nicholas), Richards, J.B. (Brent), Perry, J.R.B. (John), Tanaka, T. (Toshiko), Amin, N. (Najaf), Kollerits, B. (Barbara), Pichler, I. (Irene), Oostra, B.A. (Ben), Thorand, B. (Barbara), Frants, R.R. (Rune), Illig, T. (Thomas), Dupuis, J. (Josée), Glaser, B. (Beate), Spector, T.D. (Timothy), Guralnik, J.M. (Jack), Egan, J.M. (Josephine), Florez, J.C. (Jose), Evans, D.M. (David), Soranzo, N. (Nicole), Bandinelli, S. (Stefania), Carlson, O.D. (Olga), Frayling, T.M. (Timothy), Burling, K.A. (Keith), Smith, A.V. (Davey), Mooser, V. (Vincent), Ferrucci, L. (Luigi), Meigs, J.B. (James), Vollenweider, P. (Peter), Dijk, K.W.v., Pramstaller, P.P. (Peter Paul), Kronenberg, F. (Florian), and Tikka-Kleemola, P. (Päivi)
- Abstract
Objective: Plasma adiponectin is strongly associated with various components of metabolic syndrome, type 2 diabetes and cardiovascular outcomes. Concentrations are highly heritable and differ between men and women. We therefore aimed to investigate the genetics of plasma adiponectin in men and women. Methods: We combined genome-wide association scans of three population-based studies including 4659 persons. For the replication stage in 13795 subjects, we selected the 20 top signals of the combined analysis, as well as the 10 top signals with p-values less than 1.0 × 10-4for each the men- and the women-specific analyses. We further selected 73 SNPs that were consistently associated with metabolic syndrome parameters in previous genome-wide association studies to check for their association wit
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- 2010
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35. Genetic variants influencing circulating lipid levels and risk of coronary artery disease
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Waterworth, D. (Dawn), Ricketts, S.L. (Sally), Song, K. (Kijoung), Chen, L. (Leslie), Zhao, J.H. (Jing Hua), Ripatti, S. (Samuli), Aulchenko, Y.S. (Yurii), Zhang, W. (Weihua), Yuan, X. (Xin), Lim, N. (Noha), Luan, J., Ashford, S. (Sofie), Wheeler, E. (Eleanor), Young, E.H. (Elizabeth), Hadley, D. (David), Thompson, J.R. (John), Braund, P.S. (Peter), Johnson, T. (Toby), Struchalin, M.V. (Maksim), Surakka, I. (Ida), Luben, R.N. (Robert), Khaw, K-T. (Kay-Tee), Rodwell, S.A. (Sheila), Loos, R.J.F. (Ruth), Boekholdt, S.M. (Matthijs), Inouye, M. (Michael), Deloukas, P. (Panagiotis), Elliott, P. (Paul), Schlessinger, D., Sanna, S. (Serena), Scuteri, A. (Angelo), Jackson, A.U. (Anne), Mohlke, K.L. (Karen), Tuomilehto, J. (Jaakko), Roberts, R. (Robert), Stewart, A. (Alison), Kesaniemi, Y.A. (Antero), Mahley, R. (Robert), Grundy, S.M. (Scott), McArdle, W.L. (Wendy), Cardon, L. (Lon), Waeber, G. (Gérard), Vollenweider, P. (Peter), Chambers, J.C. (John), Boehnke, M. (Michael), Abecasis, G.R. (Gonçalo), Salomaa, V. (Veikko), Järvelin, M.R., Ruokonen, A. (Aimo), Barroso, I.E. (Inês), Epstein, S.E. (Stephen), Hakonarson, H. (Hakon), Rader, D.J. (Daniel), Reilly, M.P. (Muredach), Witteman, J.C.M. (Jacqueline), Hall, A.S. (Alistair), Samani, N.J. (Nilesh), Strachan, D.P. (David), Barter, P. (Phil), Tikka-Kleemola, P. (Päivi), Kooner, J.S. (Jaspal), Peltonen, L. (Leena Johanna), Wareham, N.J. (Nick), McPherson, R. (Ruth), Mooser, V. (Vincent), Sandhu, M.S. (Manjinder), Waterworth, D. (Dawn), Ricketts, S.L. (Sally), Song, K. (Kijoung), Chen, L. (Leslie), Zhao, J.H. (Jing Hua), Ripatti, S. (Samuli), Aulchenko, Y.S. (Yurii), Zhang, W. (Weihua), Yuan, X. (Xin), Lim, N. (Noha), Luan, J., Ashford, S. (Sofie), Wheeler, E. (Eleanor), Young, E.H. (Elizabeth), Hadley, D. (David), Thompson, J.R. (John), Braund, P.S. (Peter), Johnson, T. (Toby), Struchalin, M.V. (Maksim), Surakka, I. (Ida), Luben, R.N. (Robert), Khaw, K-T. (Kay-Tee), Rodwell, S.A. (Sheila), Loos, R.J.F. (Ruth), Boekholdt, S.M. (Matthijs), Inouye, M. (Michael), Deloukas, P. (Panagiotis), Elliott, P. (Paul), Schlessinger, D., Sanna, S. (Serena), Scuteri, A. (Angelo), Jackson, A.U. (Anne), Mohlke, K.L. (Karen), Tuomilehto, J. (Jaakko), Roberts, R. (Robert), Stewart, A. (Alison), Kesaniemi, Y.A. (Antero), Mahley, R. (Robert), Grundy, S.M. (Scott), McArdle, W.L. (Wendy), Cardon, L. (Lon), Waeber, G. (Gérard), Vollenweider, P. (Peter), Chambers, J.C. (John), Boehnke, M. (Michael), Abecasis, G.R. (Gonçalo), Salomaa, V. (Veikko), Järvelin, M.R., Ruokonen, A. (Aimo), Barroso, I.E. (Inês), Epstein, S.E. (Stephen), Hakonarson, H. (Hakon), Rader, D.J. (Daniel), Reilly, M.P. (Muredach), Witteman, J.C.M. (Jacqueline), Hall, A.S. (Alistair), Samani, N.J. (Nilesh), Strachan, D.P. (David), Barter, P. (Phil), Tikka-Kleemola, P. (Päivi), Kooner, J.S. (Jaspal), Peltonen, L. (Leena Johanna), Wareham, N.J. (Nick), McPherson, R. (Ruth), Mooser, V. (Vincent), and Sandhu, M.S. (Manjinder)
- Abstract
OBJECTIVE-: Genetic studies might provide new insights into the biological mechanisms underlying lipid metabolism and risk of CAD. We therefore conducted a genome-wide association study to identify novel genetic determinants of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides. METHODS
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- 2010
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36. Separating the mechanism-based and off-target actions of cholesteryl ester transfer protein inhibitors with CETP gene polymorphisms
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Sofat, R. (Reecha), Hingorani, A. (Aroon), Smeeth, L. (Liam), Humphries, S.E. (Steve), Talmud, P.J., Cooper, J. (Jim), Shah, T. (Tina), Sandhu, M.S. (Manjinder), Ricketts, S.L. (Sally), Boekholdt, S.M. (Matthijs), Wareham, N.J. (Nick), Khaw, K-T. (Kay-Tee), Kumari, M. (Meena), Kivimaki, M. (Mika), Marmot, M. (Michael), Asselbergs, F.W. (Folkert), Harst, P. (Pim) van der, Dullaart, R.P.F. (Robin), Navis, G. (Gerjan), Veldhuisen, D.J. (Dirk) van, Gilst, W.H. (Wiek) van, Thompson, J.F. (John), McCaskie, P. (Pamela), Palmer, C. (Cameron), Arca, M. (Marcello), Quagliarini, F. (Fabiana), Gaudio, C. (Carlo), Cambien, F. (François), Nicaud, V., Poirer, O. (Odette), Gudnason, V. (Vilmundur), Isaacs, A.J. (Aaron), Witteman, J.C.M. (Jacqueline), Tikka-Kleemola, P. (Päivi), Pencina, M. (Michael), Vasan, R.S. (Ramachandran Srini), D'Agostino, R.B. (Ralph), Ordovas, J.M. (Jose), Li, T.Y. (Tricia), Kakko, S. (Sakari), Kauma, H. (Heikki), Savolainen, M.J. (Markku), Kesäniemi, Y.A. (Antero), Sandhofer, A. (Anton), Paulweber, B. (Bernhard), Sorli, J.V. (Jose), Goto, A. (Akimoto), Yokoyama, S. (Shinji), Okumura, K. (Kenji), Horne, B.D. (Benjamin), Packard, C. (Chris), Freeman, D. (Dilys), Ford, I. (Ian), Sattar, N. (Naveed), McCormack, V. (Valerie), Lawlor, D.A. (Debbie), Ebrahim, S. (Shanil), Smith, A.V. (Davey), Kastelein, J.J.P. (John), Deanfield, J. (John), Casas, J.P. (Juan), Sofat, R. (Reecha), Hingorani, A. (Aroon), Smeeth, L. (Liam), Humphries, S.E. (Steve), Talmud, P.J., Cooper, J. (Jim), Shah, T. (Tina), Sandhu, M.S. (Manjinder), Ricketts, S.L. (Sally), Boekholdt, S.M. (Matthijs), Wareham, N.J. (Nick), Khaw, K-T. (Kay-Tee), Kumari, M. (Meena), Kivimaki, M. (Mika), Marmot, M. (Michael), Asselbergs, F.W. (Folkert), Harst, P. (Pim) van der, Dullaart, R.P.F. (Robin), Navis, G. (Gerjan), Veldhuisen, D.J. (Dirk) van, Gilst, W.H. (Wiek) van, Thompson, J.F. (John), McCaskie, P. (Pamela), Palmer, C. (Cameron), Arca, M. (Marcello), Quagliarini, F. (Fabiana), Gaudio, C. (Carlo), Cambien, F. (François), Nicaud, V., Poirer, O. (Odette), Gudnason, V. (Vilmundur), Isaacs, A.J. (Aaron), Witteman, J.C.M. (Jacqueline), Tikka-Kleemola, P. (Päivi), Pencina, M. (Michael), Vasan, R.S. (Ramachandran Srini), D'Agostino, R.B. (Ralph), Ordovas, J.M. (Jose), Li, T.Y. (Tricia), Kakko, S. (Sakari), Kauma, H. (Heikki), Savolainen, M.J. (Markku), Kesäniemi, Y.A. (Antero), Sandhofer, A. (Anton), Paulweber, B. (Bernhard), Sorli, J.V. (Jose), Goto, A. (Akimoto), Yokoyama, S. (Shinji), Okumura, K. (Kenji), Horne, B.D. (Benjamin), Packard, C. (Chris), Freeman, D. (Dilys), Ford, I. (Ian), Sattar, N. (Naveed), McCormack, V. (Valerie), Lawlor, D.A. (Debbie), Ebrahim, S. (Shanil), Smith, A.V. (Davey), Kastelein, J.J.P. (John), Deanfield, J. (John), and Casas, J.P. (Juan)
- Abstract
Background: Cholesteryl ester transfer protein (CETP) inhibitors raise high-density lipoprotein (HDL) cholesterol, but torcetrapib, the first-in-class inhibitor tested in a large outcome trial, caused an unexpected blood pressure elevation and increased cardiovascular events. Whether the hypertensive effect resulted from CETP inhibition or an off-target action of torcetrapib has been debated. We hypothesized that common single-nucleotide polymorphisms in the CETP gene could help distinguish mechanism-based from off-target actions of CETP inhibitors to inform on the validity of CETP as a therapeutic target. Methods and Results: We compared the effect of CETP single-nucleotide polymorphisms and torcetrapib treatment on lipid fractions, blood pressure, and electrolytes in up to 67 687 individuals from genetic studies and 17 911 from randomized trials. CETP single-nucleotide polymorphisms and torcetrapib treatment reduced CETP activity and had a directionally concordant effect on 8 lipid and lipoprotein traits (total, low-density lipoprotein, and HDL cholesterol; HDL2; HDL3; apolipoproteins A-I and B; and triglycerides), with the genetic effect on HDL cholesterol (0.13 mmol/L, 95% confidence interval [CI] 0.11 to 0.14 mmol/L) being consistent with that expected of a 10-mg dose of torcetrapib (0.13 mmol/L, 95% CI 0.10 to 0.15). In trials, 60 mg of torcetrapib elevated systolic and diastolic blood pressure by 4.47 mm Hg (95% CI 4.10 to 4.84 mm Hg) and 2.08 mm Hg (95% CI 1.84 to 2.31 mm Hg), respectively. However, the effect of CETP single-nucleotide polymorphisms on systolic blood pressure (0.16 mm Hg, 95% CI-0.28 to 0.60 mm Hg) and diastolic blood pressure (-0.04 mm Hg, 95% CI-0.36 to 0.28 mm Hg) was null and significantly different from that expected of 10 mg of torcetrapib. Conclusions: Discordance in the effects of CETP single-nucleotide polymorphisms and torcetrapib treatment on blood pressure despite the concordant effects on lipids indicates the hypertensive action
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- 2010
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37. Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies
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Elks, C.E. (Cathy), Perry, J.R.B. (John), Sulem, P. (Patrick), Chasman, D.I. (Daniel), Franceschini, N. (Nora), He, C. (Chunyan), Lunetta, K.L. (Kathryn), Visser, J.A. (Jenny), Byrne, E.M. (Enda), Cousminer, D.L. (Diana), Gudbjartsson, D.F. (Daniel), Esko, T. (Tõnu), Feenstra, B. (Bjarke), Hottenga, J.J. (Jouke Jan), Koller, D.L. (Daniel), Kutalik, Z. (Zoltán), Lin, P. (Peng), Mangino, M. (Massimo), Marongiu, M. (Mara), McArdle, P.F. (Patrick), Smith, A.V. (Albert Vernon), Stolk, L. (Lisette), Wingerden, S. (Sophie) van, Zhao, J.H. (Jing Hua), Albrecht, E. (Eva), Corre, T. (Tanguy), Ingelsson, E. (Erik), Hayward, C. (Caroline), Magnusson, P.K. (Patrik), Ulivi, S. (Shelia), Warrington, N.M. (Nicole), Zgaga, L. (Lina), Alavere, H. (Helene), Amin, N. (Najaf), Aspelund, T. (Thor), Bandinelli, S. (Stefania), Barroso, I.E. (Inês), Berenson, G. (Gerald), Bergmann, S.M. (Sven), Blackburn, H. (Hannah), Boerwinkle, E.A. (Eric), Buring, J.E. (Julie), Busonero, F., Campbell, H. (Harry), Chanock, S.J. (Stephen), Chen, W. (Wei), Cornelis, M. (Marilyn), Couper, D.J. (David), Coviello, A.D. (Andrea), Adamo, P. (Pio) d', Faire, U. (Ulf) de, Geus, E.J.C. (Eco) de, Deloukas, P. (Panagiotis), Döring, A. (Angela), Easton, D.F. (Douglas), Eiriksdottir, G. (Gudny), Emilsson, V. (Valur), Eriksson, J.G. (Johan), Ferrucci, L. (Luigi), Folsom, A.R. (Aaron), Foroud, T. (Tatiana), Garcia, M. (Melissa), Gasparini, P. (Paolo), Geller, F. (Frank), Gieger, C. (Christian), Gudnason, V. (Vilmundur), Hall, A.S. (Alistair), Hankinson, S.E. (Susan), Ferreli, L. (Liana), Heath, A.C. (Andrew), Hernandez, D.G. (Dena), Hofman, A. (Albert), Hu, F.B. (Frank), Illig, T. (Thomas), Järvelin, M.R., Johnson, A.D. (Andrew), Karasik, D. (David), Khaw, K-T. (Kay-Tee), Kiel, D.P. (Douglas), Kilpelänen, T.O. (Tuomas), Kolcic, I. (Ivana), Kraft, P. (Peter), Launer, L.J. (Lenore), Laven, J.S.E. (Joop), Li, S. (Shengxu), Liu, J. (Jianjun), Levy, D. (Daniel), Martin, N.G. (Nicholas), Melbye, M. (Mads), Mooser, V. (Vincent), Murray, J.C. (Jeffrey), Nalls, M.A. (Michael), Navarro, P. (Pau), Nelis, M. (Mari), Ness, A.R. (Andrew), Northstone, K. (Kate), Oostra, B.A. (Ben), Peacock, M. (Munro), Palmer, C. (Cameron), Palotie, A. (Aarno), Paré, G. (Guillaume), Parker, A.N. (Alex), Pedersen, N.L. (Nancy), Peltonen, L. (Leena Johanna), Pennell, C.E. (Craig), Pharoah, P.D.P. (Paul), Polasek, O. (Ozren), Plump, A.S. (Andrew), Pouta, A. (Anneli), Porcu, E. (Eleonora), Rafnar, T. (Thorunn), Rice, J.P. (John), Ring, S.M. (Susan), Rivadeneira Ramirez, F. (Fernando), Rudan, I. (Igor), Sala, C. (Cinzia), Salomaa, V. (Veikko), Sanna, S. (Serena), Schlessinger, D., Schork, N.J. (Nicholas), Scuteri, A. (Angelo), Segrè, A.V. (Ayellet), Shuldiner, A.R. (Alan), Soranzo, N. (Nicole), Sovio, U. (Ulla), Srinivasan, S.R. (Sathanur), Strachan, D.P. (David), Tammesoo, M.L., Tikkanen, E. (Emmi), Toniolo, D. (Daniela), Tsui, K. (Kim), Tryggvadottir, L. (Laufey), Tyrer, J.P. (Jonathan), Uda, M. (Manuela), Dam, R.M. (Rob) van, Meurs, J.B.J. (Joyce) van, Vollenweider, P. (Peter), Waeber, G. (Gérard), Wareham, N.J. (Nick), Waterworth, D. (Dawn), Wichmann, H.E. (Heinz Erich), Willemsen, G.A.H.M. (Gonneke), Wilson, J.F. (James), Wright, A.F. (Alan), Young, L. (Lauren), Zhai, G. (Guangju), Zhuang, W.V., Bierut, L.J. (Laura), Boomsma, D.I. (Dorret), Boyd, H.A. (Heather), Crisponi, L. (Laura), Demerath, E.W. (Ellen), Tikka-Kleemola, P. (Päivi), Econs, M.J. (Michael), Harris, T.B. (Tamara), Hunter, D. (David), Loos, R.J.F. (Ruth), Metspalu, A. (Andres), Montgomery, G.W. (Grant), Ridker, P.M. (Paul), Spector, T.D. (Timothy), Streeten, E.A. (Elizabeth), Stefansson, K. (Kari), Thorsteinsdottir, U. (Unnur), Uitterlinden, A.G. (André), Widen, E. (Elisabeth), Murabito, J. (Joanne), Ong, K. (Ken), Weedon, M.N. (Michael), Elks, C.E. (Cathy), Perry, J.R.B. (John), Sulem, P. (Patrick), Chasman, D.I. (Daniel), Franceschini, N. (Nora), He, C. (Chunyan), Lunetta, K.L. (Kathryn), Visser, J.A. (Jenny), Byrne, E.M. (Enda), Cousminer, D.L. (Diana), Gudbjartsson, D.F. (Daniel), Esko, T. (Tõnu), Feenstra, B. (Bjarke), Hottenga, J.J. (Jouke Jan), Koller, D.L. (Daniel), Kutalik, Z. (Zoltán), Lin, P. (Peng), Mangino, M. (Massimo), Marongiu, M. (Mara), McArdle, P.F. (Patrick), Smith, A.V. (Albert Vernon), Stolk, L. (Lisette), Wingerden, S. (Sophie) van, Zhao, J.H. (Jing Hua), Albrecht, E. (Eva), Corre, T. (Tanguy), Ingelsson, E. (Erik), Hayward, C. (Caroline), Magnusson, P.K. (Patrik), Ulivi, S. (Shelia), Warrington, N.M. (Nicole), Zgaga, L. (Lina), Alavere, H. (Helene), Amin, N. (Najaf), Aspelund, T. (Thor), Bandinelli, S. (Stefania), Barroso, I.E. (Inês), Berenson, G. (Gerald), Bergmann, S.M. (Sven), Blackburn, H. (Hannah), Boerwinkle, E.A. (Eric), Buring, J.E. (Julie), Busonero, F., Campbell, H. (Harry), Chanock, S.J. (Stephen), Chen, W. (Wei), Cornelis, M. (Marilyn), Couper, D.J. (David), Coviello, A.D. (Andrea), Adamo, P. (Pio) d', Faire, U. (Ulf) de, Geus, E.J.C. (Eco) de, Deloukas, P. (Panagiotis), Döring, A. (Angela), Easton, D.F. (Douglas), Eiriksdottir, G. (Gudny), Emilsson, V. (Valur), Eriksson, J.G. (Johan), Ferrucci, L. (Luigi), Folsom, A.R. (Aaron), Foroud, T. (Tatiana), Garcia, M. (Melissa), Gasparini, P. (Paolo), Geller, F. (Frank), Gieger, C. (Christian), Gudnason, V. (Vilmundur), Hall, A.S. (Alistair), Hankinson, S.E. (Susan), Ferreli, L. (Liana), Heath, A.C. (Andrew), Hernandez, D.G. (Dena), Hofman, A. (Albert), Hu, F.B. (Frank), Illig, T. (Thomas), Järvelin, M.R., Johnson, A.D. (Andrew), Karasik, D. (David), Khaw, K-T. (Kay-Tee), Kiel, D.P. (Douglas), Kilpelänen, T.O. (Tuomas), Kolcic, I. (Ivana), Kraft, P. (Peter), Launer, L.J. (Lenore), Laven, J.S.E. (Joop), Li, S. (Shengxu), Liu, J. (Jianjun), Levy, D. (Daniel), Martin, N.G. (Nicholas), Melbye, M. (Mads), Mooser, V. (Vincent), Murray, J.C. (Jeffrey), Nalls, M.A. (Michael), Navarro, P. (Pau), Nelis, M. (Mari), Ness, A.R. (Andrew), Northstone, K. (Kate), Oostra, B.A. (Ben), Peacock, M. (Munro), Palmer, C. (Cameron), Palotie, A. (Aarno), Paré, G. (Guillaume), Parker, A.N. (Alex), Pedersen, N.L. (Nancy), Peltonen, L. (Leena Johanna), Pennell, C.E. (Craig), Pharoah, P.D.P. (Paul), Polasek, O. (Ozren), Plump, A.S. (Andrew), Pouta, A. (Anneli), Porcu, E. (Eleonora), Rafnar, T. (Thorunn), Rice, J.P. (John), Ring, S.M. (Susan), Rivadeneira Ramirez, F. (Fernando), Rudan, I. (Igor), Sala, C. (Cinzia), Salomaa, V. (Veikko), Sanna, S. (Serena), Schlessinger, D., Schork, N.J. (Nicholas), Scuteri, A. (Angelo), Segrè, A.V. (Ayellet), Shuldiner, A.R. (Alan), Soranzo, N. (Nicole), Sovio, U. (Ulla), Srinivasan, S.R. (Sathanur), Strachan, D.P. (David), Tammesoo, M.L., Tikkanen, E. (Emmi), Toniolo, D. (Daniela), Tsui, K. (Kim), Tryggvadottir, L. (Laufey), Tyrer, J.P. (Jonathan), Uda, M. (Manuela), Dam, R.M. (Rob) van, Meurs, J.B.J. (Joyce) van, Vollenweider, P. (Peter), Waeber, G. (Gérard), Wareham, N.J. (Nick), Waterworth, D. (Dawn), Wichmann, H.E. (Heinz Erich), Willemsen, G.A.H.M. (Gonneke), Wilson, J.F. (James), Wright, A.F. (Alan), Young, L. (Lauren), Zhai, G. (Guangju), Zhuang, W.V., Bierut, L.J. (Laura), Boomsma, D.I. (Dorret), Boyd, H.A. (Heather), Crisponi, L. (Laura), Demerath, E.W. (Ellen), Tikka-Kleemola, P. (Päivi), Econs, M.J. (Michael), Harris, T.B. (Tamara), Hunter, D. (David), Loos, R.J.F. (Ruth), Metspalu, A. (Andres), Montgomery, G.W. (Grant), Ridker, P.M. (Paul), Spector, T.D. (Timothy), Streeten, E.A. (Elizabeth), Stefansson, K. (Kari), Thorsteinsdottir, U. (Unnur), Uitterlinden, A.G. (André), Widen, E. (Elisabeth), Murabito, J. (Joanne), Ong, K. (Ken), and Weedon, M.N. (Michael)
- Abstract
To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10 -60) and 9q31.2 (P = 2.2 × 10 -33), we identified 30 new menarche loci (all P < 5 × 10 -8) and found suggestive evidence for a further 10 loci (P < 1.9 × 10 -6). The new loci included four previously associated
- Published
- 2010
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38. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk
- Author
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Dupuis, J. (Josée), Langenberg, C. (Claudia), Prokopenko, I. (Inga), Saxena, R. (Richa), Soranzo, N. (Nicole), Jackson, A.U. (Anne), Wheeler, E. (Eleanor), Glazer, N.L. (Nicole), Bouatia-Naji, N. (Nabila), Gloyn, A.L. (Anna), Lindgren, C.M. (Cecilia), Mägi, R. (Reedik), Morris, A.P. (Andrew), Randall, J.C. (Joshua), Johnson, T. (Toby), Elliott, P. (Paul), Rybin, D. (Denis), Thorleifsson, G. (Gudmar), Steinthorsdottir, V. (Valgerdur), Henneman, P. (Peter), Grallert, H. (Harald), Dehghan, A. (Abbas), JanHottenga, J. (Jouke), Franklin, C.S. (Christopher), Navarro, P. (Pau), Song, K. (Kijoung), Goel, A. (Anuj), Perry, J.R.B. (John), Egan, J.M. (Josephine), Lajunen, T. (Taina), Grarup, N. (Niels), Sparsø, T. (Thomas), Doney, A.S.F. (Alex), Voight, B.F. (Benjamin), Stringham, H.M. (Heather), Li, M. (Man), Kanoni, S. (Stavroula), Shrader, P. (Peter), Cavalcanti-Proença, C. (Christine), Kumari, M. (Meena), Qi, L. (Lu), Timpson, N.J. (Nicholas), Gieger, C. (Christian), Zabena, C. (Carina), Rocheleau, G. (Ghislain), Ingelsson, E. (Erik), An, P. (Ping), O´Connell, J.R., Luan, J., McCarroll, S.A. (Steven), Payne, F. (Felicity), Roccasecca, R.M., Pattou, F. (François), Sethupathy, P. (Praveen), Ardlie, K.G. (Kristin), Ariyurek, Y. (Yavuz), Balkau, B. (Beverley), Barter, P. (Phil), Beilby, J.P. (John), Ben-Shlomo, Y., Benediktsson, R. (Rafn), Bennett, A.J. (Amanda), Bergmann, S.M. (Sven), Bochud, M. (Murielle), Boerwinkle, E.A. (Eric), Bonnefond, A. (Amélie), Bonnycastle, L.L. (Lori), Borch-Johnsen, K., Böttcher, Y. (Yvonne), Brunner, E. (Eric), Bumpstead, S. (Suzannah), Charpentier, G. (Guillaume), IdaChen, Y. (Yii) der, Chines, P.S. (Peter), Clarke, R., McOin, L.J. (Lachlan), Cooper, M.N. (Matthew), Cornelis, M. (Marilyn), Crawford, G. (Gabe), Crisponi, L. (Laura), Day, I.N.M. (Ian), Geus, E.J.C. (Eco) de, Delplanque, J. (Jerome), Dina, C. (Christian), Erdos, M.R. (Michael), Fedson, A.C. (Annette), Fischer-Rosinsky, A. (Antje), Forouhi, N.G. (Nita), Fox, C.S. (Caroline), Frants, R.R. (Rune), GraziaFranzosi, M. (Maria), Galan, P. (Pilar), Goodarzi, M. (Mark), Graessler, J. (Jürgen), Groves, C.J. (Christopher), Grundy, S.M. (Scott), Gwilliam, R. (Rhian), Gyllensten, U. (Ulf), Hadjadj, S. (Samy), Hallmans, G. (Göran), Hammond, N. (Naomi), Han, X. (Xijing), Hartikainen, A.-L. (Anna-Liisa), Hassanali, N. (Neelam), Hayward, C. (Caroline), Heath, S.C. (Simon), Hercberg, S. (Serge), Herder, C. (Christian), Hicks, A.A. (Andrew), Hillman, D.R. (David), Hingorani, A. (Aroon), Hofman, A. (Albert), Hui, J. (Jennie), Hung, J. (Judy), Isomaa, B. (Bo), Jørgensen, T. (Torben), Jula, A. (Antti), Kaakinen, M. (Marika), Kaprio, J. (Jaakko), AnteroKesaniemi, Y., Kivimaki, M. (Mika), Knight, B. (Beatrice), Koskinen, S. (Seppo), Kovacs, P. (Peter), Kyvik, K.O. (Kirsten Ohm), Lathrop, G.M. (Mark), Lawlor, D.A. (Debbie), Bacquer, O.L. (Olivier), Lecoeur, C. (Cécile), Lyssenko, V. (Valeriya), Mahley, R. (Robert), Mangino, M. (Massimo), Manning, A.K. (Alisa), TeresaMartínez-Larrad, M. (María), McAteer, J.B. (Jarred), McCulloch, L.J. (Laura), McPherson, R. (Ruth), Meisinger, C. (Christa), Melzer, D. (David), Meyre, D. (David), Mitchell, B.D. (Braxton), Morken, M.A. (Mario), Mukherjee, S. (Sutapa), Naitza, S. (Silvia), Narisu, N. (Narisu), Neville, M.J. (Matthew), Oostra, B.A. (Ben), Orrù, M. (Marco), Pakyz, R. (Ruth), Palmer, C.N.A. (Colin), Paolisso, G. (Giuseppe), Pattaro, C. (Cristian), Pearson, D. (Daniel), Peden, J. (John), Pedersen, N.L. (Nancy), Perola, M. (Markus), Pfeiffer, A.F.H. (Andreas), Pichler, I. (Irene), Polasek, O. (Ozren), Posthuma, D. (Danielle), Potter, S.C. (Simon), Pouta, A. (Anneli), Province, M.A. (Mike), Psaty, B.M. (Bruce), Rathmann, W. (Wolfgang), Rayner, N.W. (Nigel William), Rice, K. (Kenneth), Ripatti, S. (Samuli), Rivadeneira Ramirez, F. (Fernando), Roden, M. (Michael), Rolandsson, O. (Olov), Sandbaek, A. (Annelli), Sandhu, M.S. (Manjinder), Sanna, S. (Serena), Sayer, A.A., Scheet, P. (Paul), Scott, L.J. (Laura), Seedorf, U. (Udo), Sharp, S.J. (Stephen), Shields, B.M. (Beverley), Sigursson, G. (Gunnar), Sijbrands, E.J.G. (Eric), Silveira, A. (Angela), Simpson, L. (Laila), Singleton, A. (Andrew), Smith, N.L. (Nicholas), Sovio, U. (Ulla), Swift, A.J. (Amy), Syddall, H. (Holly), Syvänen, A.-C. (Ann-Christine), Tanaka, T. (Toshiko), Thorand, B. (Barbara), Tichet, J. (Jean), Tönjes, A. (Anke), Tuomi, T. (Tiinamaija), Uitterlinden, A.G. (André), Willems van Dijk, J.A.P. (Ko), Hoek, M. (Mandy) van, Varma, D. (Dhiraj), Visvikis-Siest, S. (Sophie), Vitart, V. (Veronique), Vogelzangs, N. (Nicole), Waeber, G. (Gérard), Wagner, P.J. (Peter), Walley, A. (Andrew), BragiWalters, G., Ward, K.L. (Kim), Watkins, H. (Hugh), Weedon, M.N. (Michael), Wild, S.H. (Sarah), Willemsen, G.A.H.M. (Gonneke), Witteman, J.C.M. (Jacqueline), GYarnell, J.W. (John), Zeggini, E. (Eleftheria), Zelenika, D. (Diana), Zethelius, B. (Björn), Zhai, G. (Guangju), Zhao, J.H. (Jing Hua), Zillikens, M.C. (Carola), Borecki, I.B. (Ingrid), Loos, R.J.F. (Ruth), Meneton, P. (Pierre), Magnusson, P.K. (Patrik), Nathan, D.M. (David), Williams, G.H. (Gordon), Hattersley, A.T. (Andrew), Silander, K. (Kaisa), Salomaa, V. (Veikko), Bornstein, S.R. (Stefan), Schwarz, P. (Peter), Spranger, J. (Jürgen), Karpe, F. (Fredrik), Shuldiner, A.R. (Alan), Dedoussis, G.V. (George), Serrano-Ríos, M. (Manuel), Lind, L. (Lars), Palmer, C. (Cameron), Hu, F.B. (Frank), Franks, P.W. (Paul), Ebrahim, S. (Shanil), Marmot, M. (Michael), Kao, W.-H.L. (Linda), Pankow, J.S. (James), Sampson, M.J. (Michael), Kuusisto, J. (Johanna), Laakso, M. (Markku), Hansen, T. (Torben), Pramstaller, P.P. (Peter Paul), Wichmann, H.E. (Erich), Illig, T. (Thomas), Rudan, I. (Igor), Wright, A.F. (Alan), Stumvoll, M. (Michael), Campbell, H. (Harry), Wilson, J.F. (James), Bergman, R.N. (Richard), Buchanan, T.A. (Thomas), Collins, F.S. (Francis), Mohlke, K.L. (Karen), Tuomilehto, J. (Jaakko), Valle, T.T. (Timo), Altshuler, D. (David), Rotter, J.I. (Jerome), Siscovick, D.S. (David), Penninx, B.W.J.H. (Brenda), Boomsma, D.I. (Dorret), Deloukas, P. (Panagiotis), Spector, T.D. (Timothy), Frayling, T.M. (Timothy), Ferrucci, L. (Luigi), Kong, A. (Augustine), Thorsteinsdottir, U. (Unnur), Zwart, J-A. (John-Anker), Tikka-Kleemola, P. (Päivi), Aulchenko, Y.S. (Yurii), Cao, A. (Antonio), Scuteri, A. (Angelo), Schlessinger, D. (David), Uda, M. (Manuela), Ruokonen, A. (Aimo), Jarvelin, M.-R. (Marjo-Riitta), Waterworth, D. (Dawn), Vollenweider, P. (Peter), Peltonen, L. (Leena Johanna), Mooser, V. (Vincent), Abecasis, G.R. (Gonçalo), Wareham, N.J. (Nick), Sladek, R. (Rob), Froguel, P. (Philippe), Meigs, J.B. (James), Groop, L. (Leif), Watanabe, R.M. (Richard), Boehnke, M. (Michael), McCarthy, M.I. (Mark), Florez, J.C. (Jose), Barroso, I.E. (Inês), Dupuis, J. (Josée), Langenberg, C. (Claudia), Prokopenko, I. (Inga), Saxena, R. (Richa), Soranzo, N. (Nicole), Jackson, A.U. (Anne), Wheeler, E. (Eleanor), Glazer, N.L. (Nicole), Bouatia-Naji, N. (Nabila), Gloyn, A.L. (Anna), Lindgren, C.M. (Cecilia), Mägi, R. (Reedik), Morris, A.P. (Andrew), Randall, J.C. (Joshua), Johnson, T. (Toby), Elliott, P. (Paul), Rybin, D. (Denis), Thorleifsson, G. (Gudmar), Steinthorsdottir, V. (Valgerdur), Henneman, P. (Peter), Grallert, H. (Harald), Dehghan, A. (Abbas), JanHottenga, J. (Jouke), Franklin, C.S. (Christopher), Navarro, P. (Pau), Song, K. (Kijoung), Goel, A. (Anuj), Perry, J.R.B. (John), Egan, J.M. (Josephine), Lajunen, T. (Taina), Grarup, N. (Niels), Sparsø, T. (Thomas), Doney, A.S.F. (Alex), Voight, B.F. (Benjamin), Stringham, H.M. (Heather), Li, M. (Man), Kanoni, S. (Stavroula), Shrader, P. (Peter), Cavalcanti-Proença, C. (Christine), Kumari, M. (Meena), Qi, L. (Lu), Timpson, N.J. (Nicholas), Gieger, C. (Christian), Zabena, C. (Carina), Rocheleau, G. (Ghislain), Ingelsson, E. (Erik), An, P. (Ping), O´Connell, J.R., Luan, J., McCarroll, S.A. (Steven), Payne, F. (Felicity), Roccasecca, R.M., Pattou, F. (François), Sethupathy, P. (Praveen), Ardlie, K.G. (Kristin), Ariyurek, Y. (Yavuz), Balkau, B. (Beverley), Barter, P. (Phil), Beilby, J.P. (John), Ben-Shlomo, Y., Benediktsson, R. (Rafn), Bennett, A.J. (Amanda), Bergmann, S.M. (Sven), Bochud, M. (Murielle), Boerwinkle, E.A. (Eric), Bonnefond, A. (Amélie), Bonnycastle, L.L. (Lori), Borch-Johnsen, K., Böttcher, Y. (Yvonne), Brunner, E. (Eric), Bumpstead, S. (Suzannah), Charpentier, G. (Guillaume), IdaChen, Y. (Yii) der, Chines, P.S. (Peter), Clarke, R., McOin, L.J. (Lachlan), Cooper, M.N. (Matthew), Cornelis, M. (Marilyn), Crawford, G. (Gabe), Crisponi, L. (Laura), Day, I.N.M. (Ian), Geus, E.J.C. (Eco) de, Delplanque, J. (Jerome), Dina, C. (Christian), Erdos, M.R. (Michael), Fedson, A.C. (Annette), Fischer-Rosinsky, A. (Antje), Forouhi, N.G. (Nita), Fox, C.S. (Caroline), Frants, R.R. (Rune), GraziaFranzosi, M. (Maria), Galan, P. (Pilar), Goodarzi, M. (Mark), Graessler, J. (Jürgen), Groves, C.J. (Christopher), Grundy, S.M. (Scott), Gwilliam, R. (Rhian), Gyllensten, U. (Ulf), Hadjadj, S. (Samy), Hallmans, G. (Göran), Hammond, N. (Naomi), Han, X. (Xijing), Hartikainen, A.-L. (Anna-Liisa), Hassanali, N. (Neelam), Hayward, C. (Caroline), Heath, S.C. (Simon), Hercberg, S. (Serge), Herder, C. (Christian), Hicks, A.A. (Andrew), Hillman, D.R. (David), Hingorani, A. (Aroon), Hofman, A. (Albert), Hui, J. (Jennie), Hung, J. (Judy), Isomaa, B. (Bo), Jørgensen, T. (Torben), Jula, A. (Antti), Kaakinen, M. (Marika), Kaprio, J. (Jaakko), AnteroKesaniemi, Y., Kivimaki, M. (Mika), Knight, B. (Beatrice), Koskinen, S. (Seppo), Kovacs, P. (Peter), Kyvik, K.O. (Kirsten Ohm), Lathrop, G.M. (Mark), Lawlor, D.A. (Debbie), Bacquer, O.L. (Olivier), Lecoeur, C. (Cécile), Lyssenko, V. (Valeriya), Mahley, R. (Robert), Mangino, M. (Massimo), Manning, A.K. (Alisa), TeresaMartínez-Larrad, M. (María), McAteer, J.B. (Jarred), McCulloch, L.J. (Laura), McPherson, R. (Ruth), Meisinger, C. (Christa), Melzer, D. (David), Meyre, D. (David), Mitchell, B.D. (Braxton), Morken, M.A. (Mario), Mukherjee, S. (Sutapa), Naitza, S. (Silvia), Narisu, N. (Narisu), Neville, M.J. (Matthew), Oostra, B.A. (Ben), Orrù, M. (Marco), Pakyz, R. (Ruth), Palmer, C.N.A. (Colin), Paolisso, G. (Giuseppe), Pattaro, C. (Cristian), Pearson, D. (Daniel), Peden, J. (John), Pedersen, N.L. (Nancy), Perola, M. (Markus), Pfeiffer, A.F.H. (Andreas), Pichler, I. (Irene), Polasek, O. (Ozren), Posthuma, D. (Danielle), Potter, S.C. (Simon), Pouta, A. (Anneli), Province, M.A. (Mike), Psaty, B.M. (Bruce), Rathmann, W. (Wolfgang), Rayner, N.W. (Nigel William), Rice, K. (Kenneth), Ripatti, S. (Samuli), Rivadeneira Ramirez, F. (Fernando), Roden, M. (Michael), Rolandsson, O. (Olov), Sandbaek, A. (Annelli), Sandhu, M.S. (Manjinder), Sanna, S. (Serena), Sayer, A.A., Scheet, P. (Paul), Scott, L.J. (Laura), Seedorf, U. (Udo), Sharp, S.J. (Stephen), Shields, B.M. (Beverley), Sigursson, G. (Gunnar), Sijbrands, E.J.G. (Eric), Silveira, A. (Angela), Simpson, L. (Laila), Singleton, A. (Andrew), Smith, N.L. (Nicholas), Sovio, U. (Ulla), Swift, A.J. (Amy), Syddall, H. (Holly), Syvänen, A.-C. (Ann-Christine), Tanaka, T. (Toshiko), Thorand, B. (Barbara), Tichet, J. (Jean), Tönjes, A. (Anke), Tuomi, T. (Tiinamaija), Uitterlinden, A.G. (André), Willems van Dijk, J.A.P. (Ko), Hoek, M. (Mandy) van, Varma, D. (Dhiraj), Visvikis-Siest, S. (Sophie), Vitart, V. (Veronique), Vogelzangs, N. (Nicole), Waeber, G. (Gérard), Wagner, P.J. (Peter), Walley, A. (Andrew), BragiWalters, G., Ward, K.L. (Kim), Watkins, H. (Hugh), Weedon, M.N. (Michael), Wild, S.H. (Sarah), Willemsen, G.A.H.M. (Gonneke), Witteman, J.C.M. (Jacqueline), GYarnell, J.W. (John), Zeggini, E. (Eleftheria), Zelenika, D. (Diana), Zethelius, B. (Björn), Zhai, G. (Guangju), Zhao, J.H. (Jing Hua), Zillikens, M.C. (Carola), Borecki, I.B. (Ingrid), Loos, R.J.F. (Ruth), Meneton, P. (Pierre), Magnusson, P.K. (Patrik), Nathan, D.M. (David), Williams, G.H. (Gordon), Hattersley, A.T. (Andrew), Silander, K. (Kaisa), Salomaa, V. (Veikko), Bornstein, S.R. (Stefan), Schwarz, P. (Peter), Spranger, J. (Jürgen), Karpe, F. (Fredrik), Shuldiner, A.R. (Alan), Dedoussis, G.V. (George), Serrano-Ríos, M. (Manuel), Lind, L. (Lars), Palmer, C. (Cameron), Hu, F.B. (Frank), Franks, P.W. (Paul), Ebrahim, S. (Shanil), Marmot, M. (Michael), Kao, W.-H.L. (Linda), Pankow, J.S. (James), Sampson, M.J. (Michael), Kuusisto, J. (Johanna), Laakso, M. (Markku), Hansen, T. (Torben), Pramstaller, P.P. (Peter Paul), Wichmann, H.E. (Erich), Illig, T. (Thomas), Rudan, I. (Igor), Wright, A.F. (Alan), Stumvoll, M. (Michael), Campbell, H. (Harry), Wilson, J.F. (James), Bergman, R.N. (Richard), Buchanan, T.A. (Thomas), Collins, F.S. (Francis), Mohlke, K.L. (Karen), Tuomilehto, J. (Jaakko), Valle, T.T. (Timo), Altshuler, D. (David), Rotter, J.I. (Jerome), Siscovick, D.S. (David), Penninx, B.W.J.H. (Brenda), Boomsma, D.I. (Dorret), Deloukas, P. (Panagiotis), Spector, T.D. (Timothy), Frayling, T.M. (Timothy), Ferrucci, L. (Luigi), Kong, A. (Augustine), Thorsteinsdottir, U. (Unnur), Zwart, J-A. (John-Anker), Tikka-Kleemola, P. (Päivi), Aulchenko, Y.S. (Yurii), Cao, A. (Antonio), Scuteri, A. (Angelo), Schlessinger, D. (David), Uda, M. (Manuela), Ruokonen, A. (Aimo), Jarvelin, M.-R. (Marjo-Riitta), Waterworth, D. (Dawn), Vollenweider, P. (Peter), Peltonen, L. (Leena Johanna), Mooser, V. (Vincent), Abecasis, G.R. (Gonçalo), Wareham, N.J. (Nick), Sladek, R. (Rob), Froguel, P. (Philippe), Meigs, J.B. (James), Groop, L. (Leif), Watanabe, R.M. (Richard), Boehnke, M. (Michael), McCarthy, M.I. (Mark), Florez, J.C. (Jose), and Barroso, I.E. (Inês)
- Abstract
Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.
- Published
- 2010
- Full Text
- View/download PDF
39. Biological, clinical and population relevance of 95 loci for blood lipids
- Author
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Teslovich, T.M. (Tanya), Musunuru, K. (Kiran), Smith, A.V. (Albert Vernon), Edmondson, A.C. (Andrew), Stylianou, I.M. (Ioannis), Koseki, M. (Masahiro), Pirruccello, J.P. (James), Ripatti, S. (Samuli), Chasman, D.I. (Daniel), Willer, C.J. (Cristen), Johansen, C.T. (Christopher), Fouchier, S.W. (Sigrid), Isaacs, A.J. (Aaron), Peloso, G.M. (Gina), Barbalic, M. (maja), Ricketts, S.L. (Sally), Bis, J.C. (Joshua), Aulchenko, Y.S. (Yurii), Thorleifsson, G. (Gudmar), Feitosa, M.F. (Mary Furlan), Chambers, J. (John), Orho-Melander, M. (Marju), Melander, O. (Olle), Johnson, T. (Toby), Li, X. (Xiaohui), Guo, X. (Xiuqing), Shin Cho, Y. (Yoon), Jin Go, M. (Min), Jin Kim, Y. (Young), Lee, J.Y. (Jong Young), Park, T. (Taesung), Kim, Y-J. (Yong-Jin), Sim, X. (Xueling), Twee-Hee Ong, R. (Rick), Croteau-Chonka, D.C. (Damien), Lange, L.A. (Leslie), Song, K. (Kijoung), Zhao, J.H. (Jing Hua), Yuan, X. (Xin), Luan, J., Lamina, C. (Claudia), Ziegler, A. (Andreas), Zhang, W. (Weibo), Zee, R.Y.L. (Robert), Wright, A.F. (Alan), Witteman, J.C.M. (Jacqueline), Wilson, J.F. (James), Willemsen, G.A.H.M. (Gonneke), Wichmann, H.E. (Heinz Erich), Whitfield, J. (John), Waterworth, D. (Dawn), Wareham, N.J. (Nick), Waeber, G. (Gérard), Vollenweider, P. (Peter), Voight, B.F. (Benjamin), Vitart, V. (Veronique), Uitterlinden, A.G. (André), Uda, M. (Manuela), Tuomilehto, J. (Jaakko), Thompson, J.R. (John), Tanaka, T. (Toshiko), Surakka, I. (Ida), Stringham, H.M. (Heather), Spector, T.D. (Timothy), Soranzo, N. (Nicole), Smit, J.H. (Johannes), Sinisalo, J. (Juha), Silander, K. (Kaisa), Sijbrands, E.J.G. (Eric), Scuteri, A. (Angelo), Scott, J. (James), Schlessinger, D. (David), Sanna, S. (Serena), Salomaa, V. (Veikko), Saharinen, J. (Juha), Sabatti, C. (Chiara), Ruokonen, A. (Aimo), Rudan, I. (Igor), Rose, L.M. (Lynda), Roberts, R. (Robert), Rieder, M. (Mark), Psaty, B.M. (Bruce), Pramstaller, P.P. (Peter Paul), Pichler, I. (Irene), Perola, M. (Markus), Penninx, B.W.J.H. (Brenda), Pedersen, N.L. (Nancy), Pattaro, C. (Cristian), Parker, A.N. (Alex), Pare, G. (Guillaume), Oostra, B.A. (Ben), Nieminen, M.S. (Markku), Nickerson, D.A. (Deborah), Montgomery, G.W. (Grant), Meitinger, T. (Thomas), McPherson, R. (Ruth), McCarthy, M.I. (Mark), McArdle, W.L. (Wendy), Masson, D. (David), Martin, N.G. (Nicholas), Marroni, F. (Fabio), Mangino, M. (Massimo), Magnusson, P.K. (Patrik), Lucas, G. (Gavin), Luben, R.N. (Robert), Loos, R.J.F. (Ruth), Lokki, M.L., Lettre, G. (Guillaume), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Lakatta, E. (Edward), Laaksonen, R. (Reijo), Kyvik, K.O. (Kirsten Ohm), Kronenberg, F. (Florian), König, I.R. (Inke), Khaw, K-T. (Kay-Tee), Kaprio, J. (Jaakko), Kaplan, R.C. (Robert), Johansson, A. (Åsa), Jarvelin, M.-R. (Marjo-Riitta), Cecile, A. (A.), Ingelsson, E. (Erik), Igl, W. (Wilmar), Hovingh, G.K. (Kees), Hottenga, J.J. (Jouke Jan), Hofman, A. (Albert), Hicks, A.A. (Andrew), Hengstenberg, C. (Christian), Heid, I.M. (Iris), Hayward, C. (Caroline), Havulinna, A.S. (Aki), Hastie, N. (Nick), Harris, T.B. (Tamara), Haritunians, T. (Talin), Hall, A.S. (Alistair), Gyllensten, U. (Ulf), Guiducci, C. (Candace), Groop, L. (Leif), Gonzalez, E. (Elena), Gieger, C. (Christian), Freimer, N.B. (Nelson), Ferrucci, L. (Luigi), Erdmann, J. (Jeanette), Elliott, P. (Paul), Ejebe, K.G. (Kenechi), Döring, A. (Angela), Dominiczak, A. (Anna), Demissie, S. (Serkalem), Deloukas, P. (Panagiotis), Geus, E.J.C. (Eco) de, Faire, U. (Ulf) de, Crawford, G. (Gabe), Collins, F.S. (Francis), Chen, C. (Chao), Caulfield, M. (Mark), Campbell, H. (Harry), Burtt, N.P. (Noël), Bonnycastle, L.L. (Lori), Boomsma, D.I. (Dorret), Boekholdt, S.M. (Matthijs), Bergman, R.N. (Richard), Barroso, I.E. (Inês), Bandinelli, S. (Stefania), Ballantyne, C. (Christie), Assimes, T.L. (Themistocles), Quertermous, T. (Thomas), Altshuler, D. (David), Seielstad, M. (Mark), Wong, T.Y. (Tien Yin), Tai, E.S. (Shyong), Feranil, A.B. (Alan), Kuzawa, C.W. (Christopher), Adair, L.S. (Linda), Taylor, H.A. (Herman), Borecki, I.B. (Ingrid), Gabriel, S.B. (Stacey), Holm, H. (Hilma), Thorsteinsdottir, U. (Unnur), Gudnason, V. (Vilmundur), Krauss, R.M. (Ronald), Mohlke, K.L. (Karen), Ordovas, J.M. (Jose), Munroe, P. (Patricia), Kooner, J.S. (Jaspal), Tall, A.R. (Alan), Hegele, R.A. (Robert), Kastelein, J.J.P. (John), Schadt, E.E. (Eric), Rotter, J.I. (Jerome), Boerwinkle, E.A. (Eric), Strachan, D.P. (David), Mooser, V. (Vincent), Zwart, J-A. (John-Anker), Reilly, M.P. (Muredach), Samani, N.J. (Nilesh), Schunkert, H. (Heribert), Cupples, L.A. (Adrienne), Sandhu, M.S. (Manjinder), Ridker, P.M. (Paul), Rader, D.J. (Daniel), Tikka-Kleemola, P. (Päivi), Peltonen, L. (Leena Johanna), Abecasis, G.R. (Gonçalo), Boehnke, M. (Michael), Kathiresan, S. (Sekar), O'Donnell, C.J. (Christopher), Teslovich, T.M. (Tanya), Musunuru, K. (Kiran), Smith, A.V. (Albert Vernon), Edmondson, A.C. (Andrew), Stylianou, I.M. (Ioannis), Koseki, M. (Masahiro), Pirruccello, J.P. (James), Ripatti, S. (Samuli), Chasman, D.I. (Daniel), Willer, C.J. (Cristen), Johansen, C.T. (Christopher), Fouchier, S.W. (Sigrid), Isaacs, A.J. (Aaron), Peloso, G.M. (Gina), Barbalic, M. (maja), Ricketts, S.L. (Sally), Bis, J.C. (Joshua), Aulchenko, Y.S. (Yurii), Thorleifsson, G. (Gudmar), Feitosa, M.F. (Mary Furlan), Chambers, J. (John), Orho-Melander, M. (Marju), Melander, O. (Olle), Johnson, T. (Toby), Li, X. (Xiaohui), Guo, X. (Xiuqing), Shin Cho, Y. (Yoon), Jin Go, M. (Min), Jin Kim, Y. (Young), Lee, J.Y. (Jong Young), Park, T. (Taesung), Kim, Y-J. (Yong-Jin), Sim, X. (Xueling), Twee-Hee Ong, R. (Rick), Croteau-Chonka, D.C. (Damien), Lange, L.A. (Leslie), Song, K. (Kijoung), Zhao, J.H. (Jing Hua), Yuan, X. (Xin), Luan, J., Lamina, C. (Claudia), Ziegler, A. (Andreas), Zhang, W. (Weibo), Zee, R.Y.L. (Robert), Wright, A.F. (Alan), Witteman, J.C.M. (Jacqueline), Wilson, J.F. (James), Willemsen, G.A.H.M. (Gonneke), Wichmann, H.E. (Heinz Erich), Whitfield, J. (John), Waterworth, D. (Dawn), Wareham, N.J. (Nick), Waeber, G. (Gérard), Vollenweider, P. (Peter), Voight, B.F. (Benjamin), Vitart, V. (Veronique), Uitterlinden, A.G. (André), Uda, M. (Manuela), Tuomilehto, J. (Jaakko), Thompson, J.R. (John), Tanaka, T. (Toshiko), Surakka, I. (Ida), Stringham, H.M. (Heather), Spector, T.D. (Timothy), Soranzo, N. (Nicole), Smit, J.H. (Johannes), Sinisalo, J. (Juha), Silander, K. (Kaisa), Sijbrands, E.J.G. (Eric), Scuteri, A. (Angelo), Scott, J. (James), Schlessinger, D. (David), Sanna, S. (Serena), Salomaa, V. (Veikko), Saharinen, J. (Juha), Sabatti, C. (Chiara), Ruokonen, A. (Aimo), Rudan, I. (Igor), Rose, L.M. (Lynda), Roberts, R. (Robert), Rieder, M. (Mark), Psaty, B.M. (Bruce), Pramstaller, P.P. (Peter Paul), Pichler, I. (Irene), Perola, M. (Markus), Penninx, B.W.J.H. (Brenda), Pedersen, N.L. (Nancy), Pattaro, C. (Cristian), Parker, A.N. (Alex), Pare, G. (Guillaume), Oostra, B.A. (Ben), Nieminen, M.S. (Markku), Nickerson, D.A. (Deborah), Montgomery, G.W. (Grant), Meitinger, T. (Thomas), McPherson, R. (Ruth), McCarthy, M.I. (Mark), McArdle, W.L. (Wendy), Masson, D. (David), Martin, N.G. (Nicholas), Marroni, F. (Fabio), Mangino, M. (Massimo), Magnusson, P.K. (Patrik), Lucas, G. (Gavin), Luben, R.N. (Robert), Loos, R.J.F. (Ruth), Lokki, M.L., Lettre, G. (Guillaume), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Lakatta, E. (Edward), Laaksonen, R. (Reijo), Kyvik, K.O. (Kirsten Ohm), Kronenberg, F. (Florian), König, I.R. (Inke), Khaw, K-T. (Kay-Tee), Kaprio, J. (Jaakko), Kaplan, R.C. (Robert), Johansson, A. (Åsa), Jarvelin, M.-R. (Marjo-Riitta), Cecile, A. (A.), Ingelsson, E. (Erik), Igl, W. (Wilmar), Hovingh, G.K. (Kees), Hottenga, J.J. (Jouke Jan), Hofman, A. (Albert), Hicks, A.A. (Andrew), Hengstenberg, C. (Christian), Heid, I.M. (Iris), Hayward, C. (Caroline), Havulinna, A.S. (Aki), Hastie, N. (Nick), Harris, T.B. (Tamara), Haritunians, T. (Talin), Hall, A.S. (Alistair), Gyllensten, U. (Ulf), Guiducci, C. (Candace), Groop, L. (Leif), Gonzalez, E. (Elena), Gieger, C. (Christian), Freimer, N.B. (Nelson), Ferrucci, L. (Luigi), Erdmann, J. (Jeanette), Elliott, P. (Paul), Ejebe, K.G. (Kenechi), Döring, A. (Angela), Dominiczak, A. (Anna), Demissie, S. (Serkalem), Deloukas, P. (Panagiotis), Geus, E.J.C. (Eco) de, Faire, U. (Ulf) de, Crawford, G. (Gabe), Collins, F.S. (Francis), Chen, C. (Chao), Caulfield, M. (Mark), Campbell, H. (Harry), Burtt, N.P. (Noël), Bonnycastle, L.L. (Lori), Boomsma, D.I. (Dorret), Boekholdt, S.M. (Matthijs), Bergman, R.N. (Richard), Barroso, I.E. (Inês), Bandinelli, S. (Stefania), Ballantyne, C. (Christie), Assimes, T.L. (Themistocles), Quertermous, T. (Thomas), Altshuler, D. (David), Seielstad, M. (Mark), Wong, T.Y. (Tien Yin), Tai, E.S. (Shyong), Feranil, A.B. (Alan), Kuzawa, C.W. (Christopher), Adair, L.S. (Linda), Taylor, H.A. (Herman), Borecki, I.B. (Ingrid), Gabriel, S.B. (Stacey), Holm, H. (Hilma), Thorsteinsdottir, U. (Unnur), Gudnason, V. (Vilmundur), Krauss, R.M. (Ronald), Mohlke, K.L. (Karen), Ordovas, J.M. (Jose), Munroe, P. (Patricia), Kooner, J.S. (Jaspal), Tall, A.R. (Alan), Hegele, R.A. (Robert), Kastelein, J.J.P. (John), Schadt, E.E. (Eric), Rotter, J.I. (Jerome), Boerwinkle, E.A. (Eric), Strachan, D.P. (David), Mooser, V. (Vincent), Zwart, J-A. (John-Anker), Reilly, M.P. (Muredach), Samani, N.J. (Nilesh), Schunkert, H. (Heribert), Cupples, L.A. (Adrienne), Sandhu, M.S. (Manjinder), Ridker, P.M. (Paul), Rader, D.J. (Daniel), Tikka-Kleemola, P. (Päivi), Peltonen, L. (Leena Johanna), Abecasis, G.R. (Gonçalo), Boehnke, M. (Michael), Kathiresan, S. (Sekar), and O'Donnell, C.J. (Christopher)
- Abstract
Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P<-10-8), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.
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- 2010
- Full Text
- View/download PDF
40. Genome-wide association analysis identifies multiple loci related to resting heart rate
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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
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- 2010
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41. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis
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Voight, B.F. (Benjamin), Scott, L.J. (Laura), Steinthorsdottir, V. (Valgerdur), Morris, A.D. (Andrew), Dina, C. (Christian), Welch, R.P. (Ryan), Zeggini, E. (Eleftheria), Huth, C. (Cornelia), Aulchenko, Y.S. (Yurii), Thorleifsson, G. (Gudmar), McCulloch, L.J. (Laura), Ferreira, T. (Teresa), Grallert, H. (Harald), Amin, N. (Najaf), Wu, G. (Guanming), Willer, C.J. (Cristen), Raychaudhuri, S. (Soumya), McCarroll, S.A. (Steven), Langenberg, C. (Claudia), Hofmann, O.M. (Oliver), Dupuis, J. (Josée), Qi, L. (Lu), Segrè, A.V. (Ayellet), Hoek, M. (Mandy) van, Navarro, P. (Pau), Ardlie, K.G. (Kristin), Balkau, B. (Beverley), Benediktsson, R. (Rafn), Bennett, A.J. (Amanda), Blagieva, R. (Roza), Boerwinkle, E.A. (Eric), Bonnycastle, L.L. (Lori), Boström, K.B. (Kristina Bengtsson), Bravenboer, B. (Bert), Bumpstead, S. (Suzannah), Burtt, N.P. (Noël), Charpentier, G. (Guillaume), Chines, P.S. (Peter), Cornelis, M. (Marilyn), Couper, D.J. (David), Crawford, G. (Gabe), Doney, A.S.F. (Alex), Elliott, K.S. (Katherine), Erdos, M.R. (Michael), Fox, C.S. (Caroline), Franklin, C.S. (Christopher), Ganser, M. (Martha), Gieger, C. (Christian), Grarup, N. (Niels), Green, T. (Todd), Griffin, S. (Simon), Groves, C.J. (Christopher), Guiducci, C. (Candace), Hadjadj, S. (Samy), Hassanali, N. (Neelam), Herder, C. (Christian), Isomaa, B. (Bo), Jackson, A.U. (Anne), Johnson, P.R.V. (Paul), Jørgensen, T. (Torben), Kao, W.H.L. (Wen), Klopp, N. (Norman), Kong, A. (Augustine), Kraft, P. (Peter), Kuusisto, J. (Johanna), Lauritzen, T. (Torsten), Li, M. (Man), Lieverse, A.G. (Aloysius), Lindgren, C.M. (Cecilia), Lyssenko, V. (Valeriya), Marre, M. (Michel), Meitinger, T. (Thomas), Midthjell, K. (Kristian), Morken, M.A. (Mario), Narisu, N. (Narisu), Nilsson, P. (Peter), Owen, K.R. (Katharine), Payne, F. (Felicity), Perry, J.R.B. (John), Petersen, A.K., Platou, C. (Carl), Proença, C. (Christine), Prokopenko, I. (Inga), Rathmann, W. (Wolfgang), Rayner, N.W. (Nigel William), Robertson, N.R. (Neil), Rocheleau, G. (Ghislain), Roden, M. (Michael), Sampson, M.J. (Michael), Saxena, R. (Richa), Shields, B.M. (Beverley), Shrader, P. (Peter), Sigurdsson, G. (Gunnar), Sparsø, T. (Thomas), Strassburger, K. (Klaus), Stringham, H.M. (Heather), Sun, Q. (Qi), Swift, A.J. (Amy), Thorand, B. (Barbara), Tichet, J. (Jean), Tuomi, T. (Tiinamaija), Dam, R.M. (Rob) van, Haeften, T.W. (Timon) van, Herpt, T.W. (Thijs) van, Vliet-Ostaptchouk, J.V. (Jana) van, Walters, G.B. (Bragi), Weedon, M.N. (Michael), Wijmenga, C. (Cisca), Witteman, J.C.M. (Jacqueline), Bergman, R.N. (Richard), Cauchi, S. (Stephane), Collins, F.S. (Francis), Gloyn, A.L. (Anna), Gyllensten, U. (Ulf), Hansen, T. (Torben), Hide, W.A. (Winston), Hitman, G.A. (Graham), Hofman, A. (Albert), Hunter, D. (David), Hveem, K. (Kristian), Laakso, M. (Markku), Mohlke, K.L. (Karen), Palmer, C.N.A. (Colin), Pramstaller, P.P. (Peter Paul), Rudan, I. (Igor), Sijbrands, E.J.G. (Eric), Stein, L.D. (Lincoln), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Walker, M. (Mark), Wareham, N.J. (Nick), Abecasis, G.R. (Gonçalo), Boehm, B.O. (Bernhard), Campbell, H. (Harry), Daly, M.J. (Mark), Hattersley, A.T. (Andrew), Hu, F.B. (Frank), Meigs, J.B. (James), Pankow, J.S. (James), Pedersen, O. (Oluf), Wichmann, H.E. (Erich), Barroso, I.E. (Inês), Florez, J.C. (Jose), Frayling, T.M. (Timothy), Groop, L. (Leif), Sladek, R. (Rob), Thorsteinsdottir, U. (Unnur), Wilson, J.F. (James), Illig, T. (Thomas), Froguel, P. (Philippe), Tikka-Kleemola, P. (Päivi), Zwart, J-A. (John-Anker), Altshuler, D. (David), Boehnke, M. (Michael), McCarthy, M.I. (Mark), Watanabe, R.M. (Richard), Voight, B.F. (Benjamin), Scott, L.J. (Laura), Steinthorsdottir, V. (Valgerdur), Morris, A.D. (Andrew), Dina, C. (Christian), Welch, R.P. (Ryan), Zeggini, E. (Eleftheria), Huth, C. (Cornelia), Aulchenko, Y.S. (Yurii), Thorleifsson, G. (Gudmar), McCulloch, L.J. (Laura), Ferreira, T. (Teresa), Grallert, H. (Harald), Amin, N. (Najaf), Wu, G. (Guanming), Willer, C.J. (Cristen), Raychaudhuri, S. (Soumya), McCarroll, S.A. (Steven), Langenberg, C. (Claudia), Hofmann, O.M. (Oliver), Dupuis, J. (Josée), Qi, L. (Lu), Segrè, A.V. (Ayellet), Hoek, M. (Mandy) van, Navarro, P. (Pau), Ardlie, K.G. (Kristin), Balkau, B. (Beverley), Benediktsson, R. (Rafn), Bennett, A.J. (Amanda), Blagieva, R. (Roza), Boerwinkle, E.A. (Eric), Bonnycastle, L.L. (Lori), Boström, K.B. (Kristina Bengtsson), Bravenboer, B. (Bert), Bumpstead, S. (Suzannah), Burtt, N.P. (Noël), Charpentier, G. (Guillaume), Chines, P.S. (Peter), Cornelis, M. (Marilyn), Couper, D.J. (David), Crawford, G. (Gabe), Doney, A.S.F. (Alex), Elliott, K.S. (Katherine), Erdos, M.R. (Michael), Fox, C.S. (Caroline), Franklin, C.S. (Christopher), Ganser, M. (Martha), Gieger, C. (Christian), Grarup, N. (Niels), Green, T. (Todd), Griffin, S. (Simon), Groves, C.J. (Christopher), Guiducci, C. (Candace), Hadjadj, S. (Samy), Hassanali, N. (Neelam), Herder, C. (Christian), Isomaa, B. (Bo), Jackson, A.U. (Anne), Johnson, P.R.V. (Paul), Jørgensen, T. (Torben), Kao, W.H.L. (Wen), Klopp, N. (Norman), Kong, A. (Augustine), Kraft, P. (Peter), Kuusisto, J. (Johanna), Lauritzen, T. (Torsten), Li, M. (Man), Lieverse, A.G. (Aloysius), Lindgren, C.M. (Cecilia), Lyssenko, V. (Valeriya), Marre, M. (Michel), Meitinger, T. (Thomas), Midthjell, K. (Kristian), Morken, M.A. (Mario), Narisu, N. (Narisu), Nilsson, P. (Peter), Owen, K.R. (Katharine), Payne, F. (Felicity), Perry, J.R.B. (John), Petersen, A.K., Platou, C. (Carl), Proença, C. (Christine), Prokopenko, I. (Inga), Rathmann, W. (Wolfgang), Rayner, N.W. (Nigel William), Robertson, N.R. (Neil), Rocheleau, G. (Ghislain), Roden, M. (Michael), Sampson, M.J. (Michael), Saxena, R. (Richa), Shields, B.M. (Beverley), Shrader, P. (Peter), Sigurdsson, G. (Gunnar), Sparsø, T. (Thomas), Strassburger, K. (Klaus), Stringham, H.M. (Heather), Sun, Q. (Qi), Swift, A.J. (Amy), Thorand, B. (Barbara), Tichet, J. (Jean), Tuomi, T. (Tiinamaija), Dam, R.M. (Rob) van, Haeften, T.W. (Timon) van, Herpt, T.W. (Thijs) van, Vliet-Ostaptchouk, J.V. (Jana) van, Walters, G.B. (Bragi), Weedon, M.N. (Michael), Wijmenga, C. (Cisca), Witteman, J.C.M. (Jacqueline), Bergman, R.N. (Richard), Cauchi, S. (Stephane), Collins, F.S. (Francis), Gloyn, A.L. (Anna), Gyllensten, U. (Ulf), Hansen, T. (Torben), Hide, W.A. (Winston), Hitman, G.A. (Graham), Hofman, A. (Albert), Hunter, D. (David), Hveem, K. (Kristian), Laakso, M. (Markku), Mohlke, K.L. (Karen), Palmer, C.N.A. (Colin), Pramstaller, P.P. (Peter Paul), Rudan, I. (Igor), Sijbrands, E.J.G. (Eric), Stein, L.D. (Lincoln), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Walker, M. (Mark), Wareham, N.J. (Nick), Abecasis, G.R. (Gonçalo), Boehm, B.O. (Bernhard), Campbell, H. (Harry), Daly, M.J. (Mark), Hattersley, A.T. (Andrew), Hu, F.B. (Frank), Meigs, J.B. (James), Pankow, J.S. (James), Pedersen, O. (Oluf), Wichmann, H.E. (Erich), Barroso, I.E. (Inês), Florez, J.C. (Jose), Frayling, T.M. (Timothy), Groop, L. (Leif), Sladek, R. (Rob), Thorsteinsdottir, U. (Unnur), Wilson, J.F. (James), Illig, T. (Thomas), Froguel, P. (Philippe), Tikka-Kleemola, P. (Päivi), Zwart, J-A. (John-Anker), Altshuler, D. (David), Boehnke, M. (Michael), McCarthy, M.I. (Mark), and Watanabe, R.M. (Richard)
- Abstract
By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P 5 × 10 8. These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap
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- 2010
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42. Genome-wide association study of PR interval
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Pfeufer, A. (Arne), Noord, C. (Charlotte) van, Marciante, K. (Kristin), Arking, D.E. (Dan), Larson, M.G. (Martin), Smith, A.V. (Albert Vernon), Tarasov, K.V. (Kirill), Müller, M. (Martina), Sotoodehnia, N. (Nona), Sinner, M.F. (Moritz), Verwoert, G.C. (Germaine), Li, M. (Man), Kao, W.H.L. (Wen), Köttgen, A. (Anna), Coresh, J. (Josef), Bis, J.C. (Joshua), Psaty, B.M. (Bruce), Rice, K. (Kenneth), Rotter, J.I. (Jerome), Rivadeneira Ramirez, F. (Fernando), Hofman, A. (Albert), Kors, J.A. (Jan), Stricker, B.H.Ch. (Bruno), Uitterlinden, A.G. (André), Tikka-Kleemola, P. (Päivi), Beckmann, B.M. (Britt), Sauter, W. (Wiebke), Gieger, C. (Christian), Lubitz, S.A. (Steven), Newton-Cheh, C. (Christopher), Wang, T.J. (Thomas), Magnani, J.W. (Jared), Schnabel, R. (Renate), Chung, M.K. (Mina), Barnard, J. (John), Wagoner, D.R. (David) van, Vasan, R.S. (Ramachandran Srini), Aspelund, T. (Thor), Eiriksdottir, G. (Gudny), Harris, T.B. (Tamara), Launer, L.J. (Lenore), Najjar, S.S. (Samer), Lakatta, E. (Edward), Schlessinger, D. (David), Uda, M. (Manuela), Abecasis, G.R. (Gonçalo), Artto, V. (Ville), Ehret, G.B. (Georg), Boerwinkle, E.A. (Eric), Chakravarti, A. (Aravinda), Soliman, E.Z. (Elsayed), Lunetta, K.L. (Kathryn), Perz, S. (Siegfried), Wichmann, H.E. (Erich), Meitinger, T. (Thomas), Levy, D. (Daniel), Gudnason, V. (Vilmundur), Ellinor, P.T. (Patrick), Sanna, S. (Serena), Kääb, S. (Stefan), Witteman, J.C.M. (Jacqueline), Alonso, A. (Alvaro), Benjamin, E.J. (Emelia), Heckbert, S.R. (Susan), Pfeufer, A. (Arne), Noord, C. (Charlotte) van, Marciante, K. (Kristin), Arking, D.E. (Dan), Larson, M.G. (Martin), Smith, A.V. (Albert Vernon), Tarasov, K.V. (Kirill), Müller, M. (Martina), Sotoodehnia, N. (Nona), Sinner, M.F. (Moritz), Verwoert, G.C. (Germaine), Li, M. (Man), Kao, W.H.L. (Wen), Köttgen, A. (Anna), Coresh, J. (Josef), Bis, J.C. (Joshua), Psaty, B.M. (Bruce), Rice, K. (Kenneth), Rotter, J.I. (Jerome), Rivadeneira Ramirez, F. (Fernando), Hofman, A. (Albert), Kors, J.A. (Jan), Stricker, B.H.Ch. (Bruno), Uitterlinden, A.G. (André), Tikka-Kleemola, P. (Päivi), Beckmann, B.M. (Britt), Sauter, W. (Wiebke), Gieger, C. (Christian), Lubitz, S.A. (Steven), Newton-Cheh, C. (Christopher), Wang, T.J. (Thomas), Magnani, J.W. (Jared), Schnabel, R. (Renate), Chung, M.K. (Mina), Barnard, J. (John), Wagoner, D.R. (David) van, Vasan, R.S. (Ramachandran Srini), Aspelund, T. (Thor), Eiriksdottir, G. (Gudny), Harris, T.B. (Tamara), Launer, L.J. (Lenore), Najjar, S.S. (Samer), Lakatta, E. (Edward), Schlessinger, D. (David), Uda, M. (Manuela), Abecasis, G.R. (Gonçalo), Artto, V. (Ville), Ehret, G.B. (Georg), Boerwinkle, E.A. (Eric), Chakravarti, A. (Aravinda), Soliman, E.Z. (Elsayed), Lunetta, K.L. (Kathryn), Perz, S. (Siegfried), Wichmann, H.E. (Erich), Meitinger, T. (Thomas), Levy, D. (Daniel), Gudnason, V. (Vilmundur), Ellinor, P.T. (Patrick), Sanna, S. (Serena), Kääb, S. (Stefan), Witteman, J.C.M. (Jacqueline), Alonso, A. (Alvaro), Benjamin, E.J. (Emelia), and Heckbert, S.R. (Susan)
- Abstract
The electrocardiographic PR interval (or PQ interval) reflects atrial and atrioventricular nodal conduction, disturbances of which increase risk of atrial fibrillation. We report a meta-analysis of genome-wide association studies for PR interval from seven population-based European studies in the CHARGE Consortium: AGES, ARIC, CHS, FHS, KORA, Rotterdam Study, and SardiNIA (N = 28,517). We identified nine loci associated with PR interval at P 5 × 10 8. At the 3p22.2 locus, we observed two independent associations in voltage-gated sodium channel genes, SCN10A and SCN5A. Six of the loci were near cardiac developmental genes, including CAV1-CAV2, NKX2-5 (CSX1), SOX5, WNT11, MEIS1, and TBX5-TBX3, providing pathophysiologically interesting candidate genes. Five of the loci, SCN5A, SCN10A, NKX2-5, CAV1-CAV2, and SOX5, were also associated with atrial fibrillation (N = 5,741 cases, P 0.0056). This suggests a role for common variation in ion channel and developmental genes in atrial and atrioventricular conduction as well as in susceptibility to atrial fibrillation.
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- 2010
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43. Interactions between dietary vitamin E intake and SIRT1 genetic variation influence body mass index
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Zillikens, M.C. (Carola), Meurs, J.B.J. (Joyce) van, Rivadeneira Ramirez, F. (Fernando), Hofman, A. (Albert), Oostra, B.A. (Ben), Sijbrands, E.J.G. (Eric), Witteman, J.C.M. (Jacqueline), Pols, H.A.P. (Huib), Tikka-Kleemola, P. (Päivi), Uitterlinden, A.G. (André), Zillikens, M.C. (Carola), Meurs, J.B.J. (Joyce) van, Rivadeneira Ramirez, F. (Fernando), Hofman, A. (Albert), Oostra, B.A. (Ben), Sijbrands, E.J.G. (Eric), Witteman, J.C.M. (Jacqueline), Pols, H.A.P. (Huib), Tikka-Kleemola, P. (Päivi), and Uitterlinden, A.G. (André)
- Abstract
Background: Genetic variation in SIRT1 has been associated with body mass index (BMI) and risk of obesity. SIRT1 may be influenced by diet. Objective: We studied the gene-diet interaction on BMI at the SIRT1 locus. Design: In 4575 elderly men and women in the population-based Rotterdam Study, the effect on BMI of 3 SIRT1 genetic variants (rs7895833, rs1467568, and haplotype 1) was studied in relation to dietary intakes of energy, fat, calcium, milk, antioxidant vitamins, and niacin. Results: There was no difference in energy or fat intakes by SIRT1 genotype. Significant interactions for BMI were shown between SIRT1 genetic variants and intakes of fat, vitamin E, calcium, and milk. Only the interactions between vitamin E intake and rs1467568 and haplotype 1 remained significant (P < 0.001) after Bonferroni correction for multiple testing. Further analyses across vitamin E-intake tertiles showed highly significant associations of SIRT1 genetic variants with BMI in the lowest tertile [effect sizes (in kg/m2): 0.5-0.7 per allele copy; P = 1.9 × 10-4-5.7 × 10-7] with no associations in the higher tertiles. Conclusions: Dietary vitamin E intake may modulate the relation of SIRT1 genetic variants with BMI. Associations of SIRT1 variants with BMI in the lowest tertile of vitamin E intake may be explained by low intake of this antioxidant vitamin or by other associated dietary or lifestyle habits. These data provide support that gene-diet interactions influence BMI. Replication of our findings and further in-depth studies of dietary patterns that modify SIRT1 may lead to clinical studies of dietary modification of SIRT1 to influence obesity.
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- 2010
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44. Genomic variation associated with mortality among adults of European and African ancestry with heart failure: The cohorts for heart and aging research in genomic epidemiology consortium
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Morrison, A.C. (Alanna), Felix, J.F. (Janine), Cupples, L.A. (Adrienne), Glazer, N.L. (Nicole), Loehr, L.R. (Laura), Dehghan, A. (Abbas), Demissie, S. (Serkalem), Bis, J.C. (Joshua), Rosamond, W.D. (Wayne), Aulchenko, Y.S. (Yurii), Haritunians, T. (Talin), Folsom, A.R. (Aaron), Rivadeneira Ramirez, F. (Fernando), Benjamin, E.J. (Emelia), Lumley, T. (Thomas), Couper, D.J. (David), Stricker, B.H.Ch. (Bruno), Rice, K. (Kenneth), Wang, T.J. (Thomas), Chang, P.P. (Patricia), Hofman, A. (Albert), Levy, D. (Daniel), Rotter, J.I. (Jerome), Fox, E.R. (Ervin), Uitterlinden, A.G. (André), Psaty, B.M. (Bruce), Willerson, J.T. (James), Tikka-Kleemola, P. (Päivi), Boerwinkle, E.A. (Eric), Witteman, J.C.M. (Jacqueline), Vasan, R.S. (Ramachandran Srini), Smith, N.L. (Nicholas), O'Donnell, C.J. (Christopher), Morrison, A.C. (Alanna), Felix, J.F. (Janine), Cupples, L.A. (Adrienne), Glazer, N.L. (Nicole), Loehr, L.R. (Laura), Dehghan, A. (Abbas), Demissie, S. (Serkalem), Bis, J.C. (Joshua), Rosamond, W.D. (Wayne), Aulchenko, Y.S. (Yurii), Haritunians, T. (Talin), Folsom, A.R. (Aaron), Rivadeneira Ramirez, F. (Fernando), Benjamin, E.J. (Emelia), Lumley, T. (Thomas), Couper, D.J. (David), Stricker, B.H.Ch. (Bruno), Rice, K. (Kenneth), Wang, T.J. (Thomas), Chang, P.P. (Patricia), Hofman, A. (Albert), Levy, D. (Daniel), Rotter, J.I. (Jerome), Fox, E.R. (Ervin), Uitterlinden, A.G. (André), Psaty, B.M. (Bruce), Willerson, J.T. (James), Tikka-Kleemola, P. (Päivi), Boerwinkle, E.A. (Eric), Witteman, J.C.M. (Jacqueline), Vasan, R.S. (Ramachandran Srini), Smith, N.L. (Nicholas), and O'Donnell, C.J. (Christopher)
- Abstract
Background-Prognosis and survival are significant concerns for individuals with heart failure (HF). To better understand the pathophysiology of HF prognosis, the association between 2 366 858 single-nucleotide polymorphisms (SNPs) and all-cause mortality was evaluated among individuals with incident HF from 4 community-based prospective cohorts: the Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study. Methods and Results-Participants were 2526 individuals of European ancestry
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- 2010
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45. Genome-wide association studies of serum magnesium, potassium, and sodium concentrations identify six loci influencing serum magnesium levels
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Meyer, T.E. (Tamra), Verwoert, G.C. (Germaine), Hwang, S.J., Glazer, N.L. (Nicole), Smith, A.V. (Albert Vernon), Rooij, F.J.A. (Frank) van, Ehret, G.B. (Georg), Boerwinkle, E.A. (Eric), Felix, J.F. (Janine), Leak, T.S. (Tennille), Harris, T.B. (Tamara), Yang, Q. (Qiong Fang), Dehghan, A. (Abbas), Aspelund, T. (Thor), Katz, R. (Ronit), Homuth, G. (Georg), Kocher, T. (Thomas), Rettig, R. (Rainer), Ried, J.S. (Janina), Gieger, C. (Christian), Prucha, H. (Hanna), Pfeufer, A. (Arne), Meitinger, T. (Thomas), Coresh, J. (Josef), Hofman, A. (Albert), Sarnak, M. (Mark), Chen, Y.D.I. (Yii-Der Ida), Uitterlinden, A.G. (André), Chakravarti, A. (Aravinda), Psaty, B.M. (Bruce), Tikka-Kleemola, P. (Päivi), Kao, W.-H.L. (Linda), Witteman, J.C.M. (Jacqueline), Gudnason, V. (Vilmundur), Siscovick, D.S. (David), Fox, C.S. (Caroline), Köttgen, A. (Anna), Meyer, T.E. (Tamra), Verwoert, G.C. (Germaine), Hwang, S.J., Glazer, N.L. (Nicole), Smith, A.V. (Albert Vernon), Rooij, F.J.A. (Frank) van, Ehret, G.B. (Georg), Boerwinkle, E.A. (Eric), Felix, J.F. (Janine), Leak, T.S. (Tennille), Harris, T.B. (Tamara), Yang, Q. (Qiong Fang), Dehghan, A. (Abbas), Aspelund, T. (Thor), Katz, R. (Ronit), Homuth, G. (Georg), Kocher, T. (Thomas), Rettig, R. (Rainer), Ried, J.S. (Janina), Gieger, C. (Christian), Prucha, H. (Hanna), Pfeufer, A. (Arne), Meitinger, T. (Thomas), Coresh, J. (Josef), Hofman, A. (Albert), Sarnak, M. (Mark), Chen, Y.D.I. (Yii-Der Ida), Uitterlinden, A.G. (André), Chakravarti, A. (Aravinda), Psaty, B.M. (Bruce), Tikka-Kleemola, P. (Päivi), Kao, W.-H.L. (Linda), Witteman, J.C.M. (Jacqueline), Gudnason, V. (Vilmundur), Siscovick, D.S. (David), Fox, C.S. (Caroline), and Köttgen, A. (Anna)
- Abstract
Magnesium, potassium, and sodium, cations commonly measured in serum, are involved in many physiological processes including energy metabolism, nerve and muscle function, signal transduction, and fluid and blood pressure regulation. To evaluate the contribution of common genetic variation to normal physiologic variation in serum concentrations of these cations, we conducted genome-wide association studies of serum magnesium, potassium, and sodium concentrations using ~2.5 million genotyped and imputed common single nucleotide polymorphisms (SNPs) in 15,366 parti
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- 2010
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46. Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function
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Hancock, D.B. (Dana), Eijgelsheim, M. (Mark), Wilk, J.B. (Jemma), Gharib, S.A. (Sina), Loehr, L.R. (Laura), Marciante, K. (Kristin), Franceschini, N. (Nora), Durme, Y.M.T.A. van, Chen, T.H., Barr, R.G. (Graham), Schabath, M.B. (Matthew), Couper, D.J. (David), Brusselle, G.G. (Guy), Psaty, B.M. (Bruce), Tikka-Kleemola, P. (Päivi), Rotter, J.I. (Jerome), Uitterlinden, A.G. (André), Hofman, A. (Albert), Punjabi, N.M. (Naresh), Rivadeneira Ramirez, F. (Fernando), Morrison, A.C. (Alanna), Enright, P.L. (Paul), North, K.E. (Kari), Heckbert, S.R. (Susan), Lumley, T. (Thomas), Stricker, B.H.Ch. (Bruno), O'Connor, G.T. (George), London, S.J. (Stephanie), Hancock, D.B. (Dana), Eijgelsheim, M. (Mark), Wilk, J.B. (Jemma), Gharib, S.A. (Sina), Loehr, L.R. (Laura), Marciante, K. (Kristin), Franceschini, N. (Nora), Durme, Y.M.T.A. van, Chen, T.H., Barr, R.G. (Graham), Schabath, M.B. (Matthew), Couper, D.J. (David), Brusselle, G.G. (Guy), Psaty, B.M. (Bruce), Tikka-Kleemola, P. (Päivi), Rotter, J.I. (Jerome), Uitterlinden, A.G. (André), Hofman, A. (Albert), Punjabi, N.M. (Naresh), Rivadeneira Ramirez, F. (Fernando), Morrison, A.C. (Alanna), Enright, P.L. (Paul), North, K.E. (Kari), Heckbert, S.R. (Susan), Lumley, T. (Thomas), Stricker, B.H.Ch. (Bruno), O'Connor, G.T. (George), and London, S.J. (Stephanie)
- Abstract
Spirometric measures of lung function are heritable traits that reflect respiratory health and predict morbidity and mortality. We meta-analyzed genome-wide association studies for two clinically important lung-function measures: forced expiratory volume in the first second (FEV1) and its ratio to forced vital capacity (FEV1/FVC), an indicator of airflow obstruction. This meta-analysis included 20,890 participants of European ancestry from four CHARGE Consortium studies: Atherosclerosis Risk in Communities, Cardiovascular Health Study, Framingham Heart Study and Rotterdam Study. We identified eight loci associated with FEV 1 /FVC (HHIP, GPR126, ADAM19, AGER-PPT2, FAM13A, PTCH1, PID1 and HTR4) and one locus associated with FEV1(INTS12-GSTCD-NPNT) at or near genome-wide significance (P 5 × 10-8) in the CHARGE Consortium dataset. Our findings may offer insights into pulmonary function and pathogenesis of chronic lung disease.
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- 2010
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47. Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1
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Anttila, V, Stefansson, H, Kallela, M, Todt, U, Terwindt, GM, Calafato, MS, Nyholt, DR, Dimas, AS, Freilinger, T, Mueller-Myhsok, B, Artto, V, Inouye, M, Alakurtti, K, Kaunisto, MA, Haemaelaeinen, E, de Vries, B, Stam, AH, Weller, CM, Heinze, A, Heinze-Kuhn, K, Goebel, I, Borck, G, Goebel, H, Steinberg, S, Wolf, C, Bjoernsson, A, Gudmundsson, G, Kirchmann, M, Hauge, A, Werge, T, Schoenen, J, Eriksson, JG, Hagen, K, Stovner, L, Wichmann, E, Meitinger, T, Alexander, M, Moebus, S, Schreiber, S, Aulchenko, YS, Breteler, MMB, Uitterlinden, AG, Hofman, A, van Duijn, CM, Tikka-Kleemola, P, Vepsaelaeinen, S, Lucae, S, Tozzi, F, Muglia, P, Barrett, J, Kaprio, J, Faerkkilae, M, Peltonen, L, Stefansson, K, Zwart, J-A, Ferrari, MD, Olesen, J, Daly, M, Wessman, M, van den Maagdenberg, AMJM, Dichgans, M, Kubisch, C, Dermitzakis, ET, Frants, RR, Palotie, A, Anttila, V, Stefansson, H, Kallela, M, Todt, U, Terwindt, GM, Calafato, MS, Nyholt, DR, Dimas, AS, Freilinger, T, Mueller-Myhsok, B, Artto, V, Inouye, M, Alakurtti, K, Kaunisto, MA, Haemaelaeinen, E, de Vries, B, Stam, AH, Weller, CM, Heinze, A, Heinze-Kuhn, K, Goebel, I, Borck, G, Goebel, H, Steinberg, S, Wolf, C, Bjoernsson, A, Gudmundsson, G, Kirchmann, M, Hauge, A, Werge, T, Schoenen, J, Eriksson, JG, Hagen, K, Stovner, L, Wichmann, E, Meitinger, T, Alexander, M, Moebus, S, Schreiber, S, Aulchenko, YS, Breteler, MMB, Uitterlinden, AG, Hofman, A, van Duijn, CM, Tikka-Kleemola, P, Vepsaelaeinen, S, Lucae, S, Tozzi, F, Muglia, P, Barrett, J, Kaprio, J, Faerkkilae, M, Peltonen, L, Stefansson, K, Zwart, J-A, Ferrari, MD, Olesen, J, Daly, M, Wessman, M, van den Maagdenberg, AMJM, Dichgans, M, Kubisch, C, Dermitzakis, ET, Frants, RR, and Palotie, A
- Abstract
Migraine is a common episodic neurological disorder, typically presenting with recurrent attacks of severe headache and autonomic dysfunction. Apart from rare monogenic subtypes, no genetic or molecular markers for migraine have been convincingly established. We identified the minor allele of rs1835740 on chromosome 8q22.1 to be associated with migraine (P = 5.38 × 10⁻⁹, odds ratio = 1.23, 95% CI 1.150-1.324) in a genome-wide association study of 2,731 migraine cases ascertained from three European headache clinics and 10,747 population-matched controls. The association was replicated in 3,202 cases and 40,062 controls for an overall meta-analysis P value of 1.69 × 10⁻¹¹ (odds ratio = 1.18, 95% CI 1.127-1.244). rs1835740 is located between MTDH (astrocyte elevated gene 1, also known as AEG-1) and PGCP (encoding plasma glutamate carboxypeptidase). In an expression quantitative trait study in lymphoblastoid cell lines, transcript levels of the MTDH were found to have a significant correlation to rs1835740 (P = 3.96 × 10⁻⁵, permuted threshold for genome-wide significance 7.7 × 10⁻⁵. To our knowledge, our data establish rs1835740 as the first genetic risk factor for migraine.
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- 2010
48. Type 2 diabetes gene TCF7L2 polymorphism is not associated with fetal and postnatal growth in two birth cohort studies
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Mook-Kanamori, D.O. (Dennis), Kort, S.W.K. (Sandra) de, Tikka-Kleemola, P. (Päivi), Uitterlinden, A.G. (André), Hofman, A. (Albert), Moll, H.A. (Henriëtte), Steegers-Theunissen, R.P.M. (Régine), Hokken-Koelega, A.C.S. (Anita), Jaddoe, V.W.V. (Vincent), Mook-Kanamori, D.O. (Dennis), Kort, S.W.K. (Sandra) de, Tikka-Kleemola, P. (Päivi), Uitterlinden, A.G. (André), Hofman, A. (Albert), Moll, H.A. (Henriëtte), Steegers-Theunissen, R.P.M. (Régine), Hokken-Koelega, A.C.S. (Anita), and Jaddoe, V.W.V. (Vincent)
- Abstract
Background: An inverse association between birth weight and the risk of developing type 2 diabetes (T2D) in adulthood has been reported. This association may be explained by common ge
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- 2009
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49. The rotterdam study: 2010 objectives and design update
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Hofman, A. (Albert), Breteler, M.M.B. (Monique), Tikka-Kleemola, P. (Päivi), Janssen, H.L.A. (Harry), Krestin, G.P. (Gabriel), Kuipers, E.J. (Ernst), Stricker, B.H.Ch. (Bruno), Tiemeier, H.W. (Henning), Uitterlinden, A.G. (André), Vingerling, J.R. (Hans), Witteman, J.C.M. (Jacqueline), Hofman, A. (Albert), Breteler, M.M.B. (Monique), Tikka-Kleemola, P. (Päivi), Janssen, H.L.A. (Harry), Krestin, G.P. (Gabriel), Kuipers, E.J. (Ernst), Stricker, B.H.Ch. (Bruno), Tiemeier, H.W. (Henning), Uitterlinden, A.G. (André), Vingerling, J.R. (Hans), and Witteman, J.C.M. (Jacqueline)
- Abstract
The Rotterdam Study is a prospective cohort study ongoing since 1990 in the city of Rotterdam in The Netherlands. The study targets cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric and respiratory diseases. As of 2008, 14,926 subjects aged 45 years or over comprise the Rotterdam Study cohort. The findings of the Rotterdam Study have been presented in close to a 1,000 research articles and reports (see www.epib.nl/ rotterdamstudy ). This article gives the rationale of the study and its design. It also presents a summary of the major findings and an update of the objectives and methods.
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- 2009
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50. Predicting human height by Victorian and genomic methods
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Aulchenko, Y.S. (Yurii), Struchalin, M.V. (Maksim), Belonogova, N.M. (Nadezhda), Axenovich, T.I. (Tatiana), Weedon, M.N. (Michael), Hofman, A. (Albert), Uitterlinden, A.G. (André), Kayser, M.H. (Manfred), Oostra, B.A. (Ben), Tikka-Kleemola, P. (Päivi), Janssens, A.C.J.W. (Cécile), Borodin, P.M. (Pavel), Aulchenko, Y.S. (Yurii), Struchalin, M.V. (Maksim), Belonogova, N.M. (Nadezhda), Axenovich, T.I. (Tatiana), Weedon, M.N. (Michael), Hofman, A. (Albert), Uitterlinden, A.G. (André), Kayser, M.H. (Manfred), Oostra, B.A. (Ben), Tikka-Kleemola, P. (Päivi), Janssens, A.C.J.W. (Cécile), and Borodin, P.M. (Pavel)
- Abstract
In the Victorian era, Sir Francis Galton showed that 'when dealing with the transmission of stature from parents to children, the average height of the two parents, ... is all we need care to know about them' (1886). One hundred and twenty-two years after Galton's work was published, 54 loci showing strong statistical evidence for association to human height were described, providing us with potential genomic means of human height prediction. In a population-based study of 5748 people, we find that a 54-loci genomic profile explained 4-6% of the sex- and age-adjusted height variance, and had limited ability to discriminate tall/short people, as characterized by the area under the receiver-operating characteristic curve (AUC). In a family-based study of 550 people, with both parents having height measurements, we find that the Galtonia
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- 2009
- Full Text
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