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1. Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction

Author: Ntalla, I. (Ioanna), Weng, L.-C., Cartwright, J.H. (James H.), Hall, A.W. (Amelia Weber), Sveinbjornsson, G. (Gardar), Tucker, N.R. (Nathan R.), Choi, S.H. (Seung Hoan), Chaffin, M.D. (Mark D.), Roselli, C. (Carolina), Barnes, M.J. (Michael), Mifsud, B. (Borbala), Warren, H.R. (Helen R.), Hayward, C. (Caroline), Marten, J. (Jonathan), Cranley, J.J. (James J.), Concas, M.P. (Maria Pina), Gasparini, P. (Paolo), Boutin, T. (Thibaud), Kolcic, I. (Ivana), Polasek, O. (Ozren), Rudan, I. (Igor), Araujo, N.M. (Nathalia M.), Lima-Costa, M.F. (Maria Fernanda), Ribeiro, A.L. (Antonio), Souza, R.P. (Renan P.), Tarazona-Santos, E. (Eduardo), Giedraitis, V. (Vilmantas), Ingelsson, E. (Erik), Mahajan, A. (Anubha), Morris, A.P. (Andrew), Del Greco M, F. (Fabiola), Foco, L. (Luisa), Gögele, M. (Martin), Hicks, A.A. (Andrew A.), Cook, J.P. (James P.), Kao, W.H.L. (Wen), Lindgren, C.M. (Cecilia M.), Sundström, J. (Johan), Nelson, C.P. (Christopher P.), Riaz, M.B. (Muhammad B.), Samani, N.J. (Nilesh), Sinagra, G. (Gianfranco), Ulivi, S. (Shelia), Kähönen, M. (Mika), Mishra, P.P. (Pashupati P.), Mononen, N. (Nina), Nikus, K. (Kjell), Caulfield, M. (Mark), Dominiczak, A. (Anna), Padmanabhan, S. (Sandosh), Montasser, M.E. (May E.), O’Connell, J.R. (Jeff R.), Ryan, K. (Kathleen), Shuldiner, A.R. (Alan R.), Aeschbacher, S. (Stefanie), Conen, D. (David), Risch, L. (Lorenz), Thériault, S. (Sébastien), Hutri-Kähönen, N. (Nina), Lehtimäki, T. (Terho), Lyytikäinen, L.-P. (Leo-Pekka), Raitakari, O. (Olli), Barnes, C.L.K. (Catriona L. K.), Campbell, H. (Harry), Joshi, P.K. (Peter), Wilson, J.F. (James), Isaacs, A.J. (Aaron), Kors, J.A. (Jan), Duijn, C.M. (Cornelia) van, Huang, P.L. (Paul L.), Gudnason, V. (Vilmundur), Harris, T.B. (Tamara B.), Launer, L.J. (Lenore), Smith, A.V. (Albert), Bottinger, E.P. (Erwin), Loos, R.J.F. (Ruth), Nadkarni, G. (Girish), Preuss, M. (Michael), Correa, D.D., Mei, H. (Hao), Meitinger, T. (Thomas), Müller-Nurasyid, M. (Martina), Peters, A. (Annette), Waldenberger, M. (Melanie), Mangino, M. (Massimo), Spector, T.D. (Timothy), Rienstra, S.A., van de Vegte, Y.J. (Yordi J.), Harst, P. (Pim) van der, Verweij, N. (Niek), Kääb, S. (Stefan), Schramm, K. (Katharina), Sinner, M.F. (Moritz), Strauch, K. (Konstantin), Cutler, M.J. (Michael J.), Fatkin, D. (Diane), London, B. (Barry), Olesen, M.S. (Morten S.), Roden, D.M. (Dan M.), Benjamin Shoemaker, M. (M.), Gustav Smith, J. (J.), Biggs, M.L. (M.), Bis, J.C. (Joshua), Brody, J.A. (Jennifer A.), Psaty, B.M. (Bruce), Rice, K.M. (Kenneth), Sotoodehnia, N. (Nona), Grandi, A. (Alessandro) de, Fuchsberger, C. (Christian), Penninx, B.W.J.H., Pramstaller, P.P. (Peter Paul), Ford, I. (Ian), Jukema, J.W. (Jan Wouter), Macfarlane, P.W. (Peter W.), Trompet, S. (Stella), Dörr, M. (Marcus), Felix, S.B. (Stephan B.), Völker, U. (Uwe), Weiss, S. (Stefan), Havulinna, A.S. (Aki), Jula, A. (Antti), Sääksjärvi, K. (K.), Salomaa, V. (Veikko), Guo, X. (Xiuqing), Heckbert, S.R. (Susan), Lin, H.J. (Henry J.), Rotter, J.I. (Jerome I.), Taylor, K.D. (Kent), Yao, J. (Jie), Mutsert, R. (Reneé) de, Maan, A.C. (Arie C.), Mook-Kanamori, D.O. (Dennis O.), Noordam, R. (Raymond), Cucca, F. (Francesco), Ding, J. (Jun), Lakatta, E. (Edward), Qian, Y. (Yong), Tarasov, K.V. (Kirill V.), Levy, D. (Daniel), Lin, H. (Honghuang), Newton-Cheh, C. (Christopher), Lunetta, K.L. (Kathryn), Murray, A.D. (Alison D.), Porteous, D.J. (David J.), Smith, B.H. (Blair), Stricker, B.H.Ch. (Bruno), Uitterlinden, A.G. (André), Berg, M.E. (Marten) van den, Haessler, J. (Jeff), Jackson, R.D. (Rebecca), Kooperberg, C. (Charles), Peters, U. (Ulrike), Reiner, A.P. (Alexander P.), Whitsel, E.A. (Eric), Alonso, A. (Alvaro), Arking, D.E. (Dan E.), Boerwinkle, E.A. (Eric), Ehret, G.B. (Georg B.), Soliman, E.Z. (Elsayed Z.), Avery, C.L., Gogarten, S.M., Kerr, K.F. (Kathleen), Laurie, C.C. (Cathy C.), Seyerle, A.A. (Amanda A.), Stilp, A. (Adrienne), Assa, S. (Solmaz), Abdullah Said, M. (M.), Yldau van der Ende, M. (M.), Lambiase, P.D. (Pier), Orini, M. (Michele), Ramirez, J. (Julia), Van Duijvenboden, S. (Stefan), Arnar, D.O. (David O.), Gudbjartsson, D.F. (Daniel), Holm, H. (Hilma), Sulem, P. (Patrick), Thorleifsson, G. (Gudmar), Thorolfsdottir, R.B. (Rosa B.), Thorsteinsdottir, U. (Unnur), Benjamin, E.J. (Emelia J.), Tinker, A. (Andrew), Zwart, J-A. (John-Anker), Ellinor, P.T. (Patrick), Jamshidi, Y. (Yalda), Lubitz, S.A. (Steven), Munroe, P. (Patricia), Ntalla, I. (Ioanna), Weng, L.-C., Cartwright, J.H. (James H.), Hall, A.W. (Amelia Weber), Sveinbjornsson, G. (Gardar), Tucker, N.R. (Nathan R.), Choi, S.H. (Seung Hoan), Chaffin, M.D. (Mark D.), Roselli, C. (Carolina), Barnes, M.J. (Michael), Mifsud, B. (Borbala), Warren, H.R. (Helen R.), Hayward, C. (Caroline), Marten, J. (Jonathan), Cranley, J.J. (James J.), Concas, M.P. (Maria Pina), Gasparini, P. (Paolo), Boutin, T. (Thibaud), Kolcic, I. (Ivana), Polasek, O. (Ozren), Rudan, I. (Igor), Araujo, N.M. (Nathalia M.), Lima-Costa, M.F. (Maria Fernanda), Ribeiro, A.L. (Antonio), Souza, R.P. (Renan P.), Tarazona-Santos, E. (Eduardo), Giedraitis, V. (Vilmantas), Ingelsson, E. (Erik), Mahajan, A. (Anubha), Morris, A.P. (Andrew), Del Greco M, F. (Fabiola), Foco, L. (Luisa), Gögele, M. (Martin), Hicks, A.A. (Andrew A.), Cook, J.P. (James P.), Kao, W.H.L. (Wen), Lindgren, C.M. (Cecilia M.), Sundström, J. (Johan), Nelson, C.P. (Christopher P.), Riaz, M.B. (Muhammad B.), Samani, N.J. (Nilesh), Sinagra, G. (Gianfranco), Ulivi, S. (Shelia), Kähönen, M. (Mika), Mishra, P.P. (Pashupati P.), Mononen, N. (Nina), Nikus, K. (Kjell), Caulfield, M. (Mark), Dominiczak, A. (Anna), Padmanabhan, S. (Sandosh), Montasser, M.E. (May E.), O’Connell, J.R. (Jeff R.), Ryan, K. (Kathleen), Shuldiner, A.R. (Alan R.), Aeschbacher, S. (Stefanie), Conen, D. (David), Risch, L. (Lorenz), Thériault, S. (Sébastien), Hutri-Kähönen, N. (Nina), Lehtimäki, T. (Terho), Lyytikäinen, L.-P. (Leo-Pekka), Raitakari, O. (Olli), Barnes, C.L.K. (Catriona L. K.), Campbell, H. (Harry), Joshi, P.K. (Peter), Wilson, J.F. (James), Isaacs, A.J. (Aaron), Kors, J.A. (Jan), Duijn, C.M. (Cornelia) van, Huang, P.L. (Paul L.), Gudnason, V. (Vilmundur), Harris, T.B. (Tamara B.), Launer, L.J. (Lenore), Smith, A.V. (Albert), Bottinger, E.P. (Erwin), Loos, R.J.F. (Ruth), Nadkarni, G. (Girish), Preuss, M. (Michael), Correa, D.D., Mei, H. (Hao), Meitinger, T. (Thomas), Müller-Nurasyid, M. (Martina), Peters, A. (Annette), Waldenberger, M. (Melanie), Mangino, M. (Massimo), Spector, T.D. (Timothy), Rienstra, S.A., van de Vegte, Y.J. (Yordi J.), Harst, P. (Pim) van der, Verweij, N. (Niek), Kääb, S. (Stefan), Schramm, K. (Katharina), Sinner, M.F. (Moritz), Strauch, K. (Konstantin), Cutler, M.J. (Michael J.), Fatkin, D. (Diane), London, B. (Barry), Olesen, M.S. (Morten S.), Roden, D.M. (Dan M.), Benjamin Shoemaker, M. (M.), Gustav Smith, J. (J.), Biggs, M.L. (M.), Bis, J.C. (Joshua), Brody, J.A. (Jennifer A.), Psaty, B.M. (Bruce), Rice, K.M. (Kenneth), Sotoodehnia, N. (Nona), Grandi, A. (Alessandro) de, Fuchsberger, C. (Christian), Penninx, B.W.J.H., Pramstaller, P.P. (Peter Paul), Ford, I. (Ian), Jukema, J.W. (Jan Wouter), Macfarlane, P.W. (Peter W.), Trompet, S. (Stella), Dörr, M. (Marcus), Felix, S.B. (Stephan B.), Völker, U. (Uwe), Weiss, S. (Stefan), Havulinna, A.S. (Aki), Jula, A. (Antti), Sääksjärvi, K. (K.), Salomaa, V. (Veikko), Guo, X. (Xiuqing), Heckbert, S.R. (Susan), Lin, H.J. (Henry J.), Rotter, J.I. (Jerome I.), Taylor, K.D. (Kent), Yao, J. (Jie), Mutsert, R. (Reneé) de, Maan, A.C. (Arie C.), Mook-Kanamori, D.O. (Dennis O.), Noordam, R. (Raymond), Cucca, F. (Francesco), Ding, J. (Jun), Lakatta, E. (Edward), Qian, Y. (Yong), Tarasov, K.V. (Kirill V.), Levy, D. (Daniel), Lin, H. (Honghuang), Newton-Cheh, C. (Christopher), Lunetta, K.L. (Kathryn), Murray, A.D. (Alison D.), Porteous, D.J. (David J.), Smith, B.H. (Blair), Stricker, B.H.Ch. (Bruno), Uitterlinden, A.G. (André), Berg, M.E. (Marten) van den, Haessler, J. (Jeff), Jackson, R.D. (Rebecca), Kooperberg, C. (Charles), Peters, U. (Ulrike), Reiner, A.P. (Alexander P.), Whitsel, E.A. (Eric), Alonso, A. (Alvaro), Arking, D.E. (Dan E.), Boerwinkle, E.A. (Eric), Ehret, G.B. (Georg B.), Soliman, E.Z. (Elsayed Z.), Avery, C.L., Gogarten, S.M., Kerr, K.F. (Kathleen), Laurie, C.C. (Cathy C.), Seyerle, A.A. (Amanda A.), Stilp, A. (Adrienne), Assa, S. (Solmaz), Abdullah Said, M. (M.), Yldau van der Ende, M. (M.), Lambiase, P.D. (Pier), Orini, M. (Michele), Ramirez, J. (Julia), Van Duijvenboden, S. (Stefan), Arnar, D.O. (David O.), Gudbjartsson, D.F. (Daniel), Holm, H. (Hilma), Sulem, P. (Patrick), Thorleifsson, G. (Gudmar), Thorolfsdottir, R.B. (Rosa B.), Thorsteinsdottir, U. (Unnur), Benjamin, E.J. (Emelia J.), Tinker, A. (Andrew), Zwart, J-A. (John-Anker), Ellinor, P.T. (Patrick), Jamshidi, Y. (Yalda), Lubitz, S.A. (Steven), and Munroe, P. (Patricia)
Abstract: The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduc
Published: 2020
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2. Pharmacogenomics of statin-related myopathy: Meta-analysis of rare variants from whole-exome sequencing

Author: Floyd, J.S. (James S.), Bloch, K.M. (Katarzyna M.), Brody, J.A. (Jennifer A.), Maroteau, C. (Cyrielle), Siddiqui, M.K. (Moneeza K.), Gregory, R. (Richard), Carr, D.F. (Daniel F.), Molokhia, M. (Mariam), Liu, X. (Xiaoming), Bis, J.C. (Joshua), Ahmed, A. (Ammar), Liu, X. (Xuan), Hallberg, P. (Pär), Yue, Q. (Qunying), Magnusson, P.K. (Patrik), Brisson, D. (Diane), Wiggins, K.L. (Kerri L.), Morrison, A.C. (Alanna C.), Khoury, E. (Etienne), Mckeigue, P.M. (Paul), Stricker, B.H.Ch. (Bruno), Lapeyre-Mestre, M. (Maryse), Heckbert, S.R. (Susan), Gallagher, A.M. (Arlene M.), Chinoy, H. (Hector), Gibbs, R.A. (Richard), Bondon-Guitton, E. (Emmanuelle), Tracy, R.P. (Russell), Boerwinkle, E.A. (Eric), Gaudet, D. (Daniel), Conforti, A. (Anita), Staa, T.P. (Tjeerd) van, Sitlani, C.M. (Colleen M.), Rice, K.M. (Kenneth M.), Maitland-van der Zee, A-H. (Anke-Hilse), Wadelius, M. (Mia), Morris, A.P. (Andrew), Pirmohamed, M. (Munir), Palmer, C.A.N. (Colin A N), Psaty, B.M. (Bruce M.), Alfirevic, A. (Ana), Floyd, J.S. (James S.), Bloch, K.M. (Katarzyna M.), Brody, J.A. (Jennifer A.), Maroteau, C. (Cyrielle), Siddiqui, M.K. (Moneeza K.), Gregory, R. (Richard), Carr, D.F. (Daniel F.), Molokhia, M. (Mariam), Liu, X. (Xiaoming), Bis, J.C. (Joshua), Ahmed, A. (Ammar), Liu, X. (Xuan), Hallberg, P. (Pär), Yue, Q. (Qunying), Magnusson, P.K. (Patrik), Brisson, D. (Diane), Wiggins, K.L. (Kerri L.), Morrison, A.C. (Alanna C.), Khoury, E. (Etienne), Mckeigue, P.M. (Paul), Stricker, B.H.Ch. (Bruno), Lapeyre-Mestre, M. (Maryse), Heckbert, S.R. (Susan), Gallagher, A.M. (Arlene M.), Chinoy, H. (Hector), Gibbs, R.A. (Richard), Bondon-Guitton, E. (Emmanuelle), Tracy, R.P. (Russell), Boerwinkle, E.A. (Eric), Gaudet, D. (Daniel), Conforti, A. (Anita), Staa, T.P. (Tjeerd) van, Sitlani, C.M. (Colleen M.), Rice, K.M. (Kenneth M.), Maitland-van der Zee, A-H. (Anke-Hilse), Wadelius, M. (Mia), Morris, A.P. (Andrew), Pirmohamed, M. (Munir), Palmer, C.A.N. (Colin A N), Psaty, B.M. (Bruce M.), and Alfirevic, A. (Ana)
Abstract: AIMS: Statin-related myopathy (SRM), which includes rhabdomyolysis, is an uncommon but important adverse drug reaction because the number of people prescribed statins world-wide is large. Previous association studies of common genetic variants have had limited success in identifying a genetic basis for this adverse drug reaction. We conducted a multi-site whole-exome sequencing study to investigate whether rare coding variants confer an increased risk of SRM. METHODS AND RESULTS: SRM 3-5 cases (N = 505) and statin treatment-tolerant controls (N = 2047) were recruited from multiple sites in North America and Europe. SRM 3-5 was defined as symptoms consistent with muscle injury and an elevated creatine phosphokinase level >4 times upper limit of normal without another likely cause of muscle injury. Whole-exome sequencing and variant calling was coordinated from two analysis centres, and results of single-variant and gene-based burden tests were meta-analysed. No genome-wide significant associations were identified. Given the large number of cases, we had 80% power to identify a variant with minor allele frequency of 0.01 that increases the risk of SRM 6-fold at genome-wide significance. CONCLUSIONS: In this large whole-exome sequencing study of severe statin-related muscle injury conducted to date, we did not find evidence that rare coding variants are responsible for this adverse drug reaction. Larger sample sizes would be required to identify rare variants with small effects, but it is unclear whether such findings would be clinically actionable.
Published: 2019
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3. Pharmacogenomics of statin-related myopathy: Meta-analysis of rare variants from whole-exome sequencing

Author: Floyd, J.S. (James S.), Bloch, K.M. (Katarzyna M.), Brody, J.A. (Jennifer A.), Maroteau, C. (Cyrielle), Siddiqui, M.K. (Moneeza K.), Gregory, R. (Richard), Carr, D.F. (Daniel F.), Molokhia, M. (Mariam), Liu, X. (Xiaoming), Bis, J.C. (Joshua), Ahmed, A. (Ammar), Liu, X. (Xuan), Hallberg, P. (Pär), Yue, Q. (Qunying), Magnusson, P.K. (Patrik), Brisson, D. (Diane), Wiggins, K.L. (Kerri L.), Morrison, A.C. (Alanna C.), Khoury, E. (Etienne), Mckeigue, P.M. (Paul), Stricker, B.H.Ch. (Bruno), Lapeyre-Mestre, M. (Maryse), Heckbert, S.R. (Susan), Gallagher, A.M. (Arlene M.), Chinoy, H. (Hector), Gibbs, R.A. (Richard), Bondon-Guitton, E. (Emmanuelle), Tracy, R.P. (Russell), Boerwinkle, E.A. (Eric), Gaudet, D. (Daniel), Conforti, A. (Anita), Staa, T.P. (Tjeerd) van, Sitlani, C.M. (Colleen M.), Rice, K.M. (Kenneth M.), Maitland-van der Zee, A-H. (Anke-Hilse), Wadelius, M. (Mia), Morris, A.P. (Andrew), Pirmohamed, M. (Munir), Palmer, C.A.N. (Colin A N), Psaty, B.M. (Bruce M.), Alfirevic, A. (Ana), Floyd, J.S. (James S.), Bloch, K.M. (Katarzyna M.), Brody, J.A. (Jennifer A.), Maroteau, C. (Cyrielle), Siddiqui, M.K. (Moneeza K.), Gregory, R. (Richard), Carr, D.F. (Daniel F.), Molokhia, M. (Mariam), Liu, X. (Xiaoming), Bis, J.C. (Joshua), Ahmed, A. (Ammar), Liu, X. (Xuan), Hallberg, P. (Pär), Yue, Q. (Qunying), Magnusson, P.K. (Patrik), Brisson, D. (Diane), Wiggins, K.L. (Kerri L.), Morrison, A.C. (Alanna C.), Khoury, E. (Etienne), Mckeigue, P.M. (Paul), Stricker, B.H.Ch. (Bruno), Lapeyre-Mestre, M. (Maryse), Heckbert, S.R. (Susan), Gallagher, A.M. (Arlene M.), Chinoy, H. (Hector), Gibbs, R.A. (Richard), Bondon-Guitton, E. (Emmanuelle), Tracy, R.P. (Russell), Boerwinkle, E.A. (Eric), Gaudet, D. (Daniel), Conforti, A. (Anita), Staa, T.P. (Tjeerd) van, Sitlani, C.M. (Colleen M.), Rice, K.M. (Kenneth M.), Maitland-van der Zee, A-H. (Anke-Hilse), Wadelius, M. (Mia), Morris, A.P. (Andrew), Pirmohamed, M. (Munir), Palmer, C.A.N. (Colin A N), Psaty, B.M. (Bruce M.), and Alfirevic, A. (Ana)
Abstract: AIMS: Statin-related myopathy (SRM), which includes rhabdomyolysis, is an uncommon but important adverse drug reaction because the number of people prescribed statins world-wide is large. Previous association studies of common genetic variants have had limited success in identifying a genetic basis for this adverse drug reaction. We conducted a multi-site whole-exome sequencing study to investigate whether rare coding variants confer an increased risk of SRM. METHODS AND RESULTS: SRM 3-5 cases (N = 505) and statin treatment-tolerant controls (N = 2047) were recruited from multiple sites in North America and Europe. SRM 3-5 was defined as symptoms consistent with muscle injury and an elevated creatine phosphokinase level >4 times upper limit of normal without another likely cause of muscle injury. Whole-exome sequencing and variant calling was coordinated from two analysis centres, and results of single-variant and gene-based burden tests were meta-analysed. No genome-wide significant associations were identified. Given the large number of cases, we had 80% power to identify a variant with minor allele frequency of 0.01 that increases the risk of SRM 6-fold at genome-wide significance. CONCLUSIONS: In this large whole-exome sequencing study of severe statin-related muscle injury conducted to date, we did not find evidence that rare coding variants are responsible for this adverse drug reaction. Larger sample sizes would be required to identify rare variants with small effects, but it is unclear whether such findings would be clinically actionable.
Published: 2019
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4. ExomeChip-Wide Analysis of 95 626 Individuals Identifies 10 Novel Loci Associated With QT and JT Intervals

Author: Bihlmeyer, N.A. (Nathan A.), Brody, J.A. (Jennifer A.), Smith, A.V. (Albert), Warren, H. (Helen), Lin, H. (Honghuang), Isaacs, A. (Aaron), Liu, C.-T. (Ching-Ti), Marten, J. (Jonathan), Radmanesh, F. (Farid), Hall, L.M. (Leanne M.), Grarup, N. (Niels), Mei, H. (Hao), Müller-Nurasyid, M. (Martina), Huffman, J.E. (Jennifer E.), Verweij, N. (Niek), Guo, X. (Xiuqing), Yao, J. (Jie), Li-Gao, R. (Ruifang), Berg, M.E. (Marten) van den, Weiss, S. (Stefan), Prins, B.P. (Bram P.), Setten, J. (Jessica) van, Haessler, J. (Jeff), Lyytikäinen, L.-P. (Leo-Pekka), Li, M. (Man), Alonso, A. (Alvaro), Soliman, E.Z. (Elsayed Z.), Bis, J.C. (Joshua), Austin, T. (Tom), Chen, Y.D.I. (Yii-Der Ida), Psaty, B.M. (Bruce M.), Harrris, T.B. (Tamara B.), Launer, L.J. (Lenore), Padmanabhan, S. (Sandosh), Dominiczak, A. (Anna), Huang, P.L. (Paul L.), Xie, Z. (Zhijun), Ellinor, P.T. (Patrick), Kors, J.A. (Jan), Campbell, A. (Archie), Murray, A.D. (Alison D.), Nelson, C.P. (Christopher P.), Tobin, M.D. (Martin), Bork-Jensen, J. (Jette), Hansen, T. (Torben), Pedersen, O. (Oluf), Linneberg, A. (Allan), Sinner, M.F. (Moritz), Peters, A. (Annette), Waldenberger, M. (Melanie), Meitinger, T. (Thomas), Perz, S. (Siegfried), Kolcic, I. (Ivana), Rudan, I. (Igor), Boer, R.A. (Rudolf) de, Meer, P. (Peter) van der, Lin, H.J. (Henry J.), Taylor, K.D. (Kent), Mutsert, R. (Reneé) de, Trompet, S. (Stella), Jukema, J.W. (Jan Wouter), Maan, A.C. (Arie C.), Stricker, B.H.Ch. (Bruno), Rivadeneira Ramirez, F. (Fernando), Uitterlinden, A. (André), Völker, U. (Uwe), Homuth, G. (Georg), Völzke, H. (Henry), Felix, S.B. (Stephan), Mangino, M. (Massimo), Spector, T.D. (Timothy), Bots, M.L. (Michiel), Perez, M. (Marco), Raitakari, O. (Olli), Kähönen, M. (Mika), Mononen, N. (Nina), Gudnason, V. (Vilmundur), Munroe, P. (Patricia), Lubitz, S.A. (Steven A.), Duijn, C.M. (Cornelia) van, Newton-Cheh, C. (Christopher), Hayward, C. (Caroline), Rosand, J. (Jonathan), Samani, N.J. (Nilesh J.), Kanters, J.K., Wilson, J.F. (James), Kääb, S. (Stefan), Polasek, O. (Ozren), van der Harst, P. (Pim), Heckbert, S.R. (Susan), Rotter, J.I. (Jerome I.), Mook-Kanamori, D.O. (Dennis O.), Eijgelsheim, M. (Mark), Dörr, M. (Marcus), Jamshidi, Y. (Yalda), Asselbergs, F.W. (Folkert W.), Kooperberg, C. (Charles), Lehtimäki, T. (Terho), Arking, D.E. (Dan), Sotoodehnia, N. (Nona), Bihlmeyer, N.A. (Nathan A.), Brody, J.A. (Jennifer A.), Smith, A.V. (Albert), Warren, H. (Helen), Lin, H. (Honghuang), Isaacs, A. (Aaron), Liu, C.-T. (Ching-Ti), Marten, J. (Jonathan), Radmanesh, F. (Farid), Hall, L.M. (Leanne M.), Grarup, N. (Niels), Mei, H. (Hao), Müller-Nurasyid, M. (Martina), Huffman, J.E. (Jennifer E.), Verweij, N. (Niek), Guo, X. (Xiuqing), Yao, J. (Jie), Li-Gao, R. (Ruifang), Berg, M.E. (Marten) van den, Weiss, S. (Stefan), Prins, B.P. (Bram P.), Setten, J. (Jessica) van, Haessler, J. (Jeff), Lyytikäinen, L.-P. (Leo-Pekka), Li, M. (Man), Alonso, A. (Alvaro), Soliman, E.Z. (Elsayed Z.), Bis, J.C. (Joshua), Austin, T. (Tom), Chen, Y.D.I. (Yii-Der Ida), Psaty, B.M. (Bruce M.), Harrris, T.B. (Tamara B.), Launer, L.J. (Lenore), Padmanabhan, S. (Sandosh), Dominiczak, A. (Anna), Huang, P.L. (Paul L.), Xie, Z. (Zhijun), Ellinor, P.T. (Patrick), Kors, J.A. (Jan), Campbell, A. (Archie), Murray, A.D. (Alison D.), Nelson, C.P. (Christopher P.), Tobin, M.D. (Martin), Bork-Jensen, J. (Jette), Hansen, T. (Torben), Pedersen, O. (Oluf), Linneberg, A. (Allan), Sinner, M.F. (Moritz), Peters, A. (Annette), Waldenberger, M. (Melanie), Meitinger, T. (Thomas), Perz, S. (Siegfried), Kolcic, I. (Ivana), Rudan, I. (Igor), Boer, R.A. (Rudolf) de, Meer, P. (Peter) van der, Lin, H.J. (Henry J.), Taylor, K.D. (Kent), Mutsert, R. (Reneé) de, Trompet, S. (Stella), Jukema, J.W. (Jan Wouter), Maan, A.C. (Arie C.), Stricker, B.H.Ch. (Bruno), Rivadeneira Ramirez, F. (Fernando), Uitterlinden, A. (André), Völker, U. (Uwe), Homuth, G. (Georg), Völzke, H. (Henry), Felix, S.B. (Stephan), Mangino, M. (Massimo), Spector, T.D. (Timothy), Bots, M.L. (Michiel), Perez, M. (Marco), Raitakari, O. (Olli), Kähönen, M. (Mika), Mononen, N. (Nina), Gudnason, V. (Vilmundur), Munroe, P. (Patricia), Lubitz, S.A. (Steven A.), Duijn, C.M. (Cornelia) van, Newton-Cheh, C. (Christopher), Hayward, C. (Caroline), Rosand, J. (Jonathan), Samani, N.J. (Nilesh J.), Kanters, J.K., Wilson, J.F. (James), Kääb, S. (Stefan), Polasek, O. (Ozren), van der Harst, P. (Pim), Heckbert, S.R. (Susan), Rotter, J.I. (Jerome I.), Mook-Kanamori, D.O. (Dennis O.), Eijgelsheim, M. (Mark), Dörr, M. (Marcus), Jamshidi, Y. (Yalda), Asselbergs, F.W. (Folkert W.), Kooperberg, C. (Charles), Lehtimäki, T. (Terho), Arking, D.E. (Dan), and Sotoodehnia, N. (Nona)
Abstract: BACKGROUND: QT interval, measured through a standard ECG, captures the time it takes for the cardiac ventricles to depolarize and repolarize. JT interval is the component of the QT interval that reflects ventricular repolarization alone. Prolonged QT interval has been linked to higher risk of sudden cardiac arrest. METHODS AND RESULTS: We performed an ExomeChip-wide analysis for both QT and JT intervals, including 209 449 variants, both common and rare, in 17 341 genes from the Illumina Infinium HumanExome BeadChip. We identified 10 loci that modulate QT and JT interval duration that have not been previously reported in the literature using single-variant statistical models in a meta-analysis of 95 626 individuals from 23 cohorts (comprised 83 884 European ancestry individuals, 9610 blacks, 1382 Hispanics, and 750 Asians). This brings the total number of ventricular repolarization associated loci to 45. In addition, our approach of using coding variants has highlighted the role of 17 specific genes for involvement in ventricular repolarization, 7 of which are in novel loci. CONCLUSIONS: Our analyses show a role for myocyte internal structure and interconnections in modulating QT interval duration, adding to previous known roles of potassium, sodium, and calcium ion regulation, as well as autonomic control. We anticipate that these discoveries will open new paths to the goal of making novel remedies for the prevention of lethal ventricular arrhythmias and sudden cardiac arrest.
Published: 2018
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5. GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes

Author: Franceschini, N. (Nora), Giambartolomei, C. (Claudia), Vries, P.S. (Paul) de, Finan, C. (Chris), Bis, J.C. (Joshua), Huntley, R.P. (Rachael P.), Lovering, R.C. (Ruth C.), Tajuddin, S.M. (Salman M.), Winkler, T.W. (Thomas W.), Graff, M. (Misa), Kavousi, M. (Maryam), Dale, C. (Caroline), Smith, A.V. (Albert), Hofer, E. (Edith), Leeuwen, E.M. (Elisa) van, Nolte, I.M. (Ilja), Lu, L. (Lingyi), Scholz, M. (Markus), Sargurupremraj, M. (Muralidharan), Pitkanen, N. (Niina), Franzén, O. (Oscar), Joshi, P.K. (Peter), Noordam, R. (Raymond), Marioni, R.E. (Riccardo), Hwang, S.-J. (Shih-Jen), Musani, S.K. (Solomon K.), Schminke, U. (Ulf), Palmas, W. (Walter), Isaacs, A.J. (Aaron), Correa, D.D., Zonderman, A.B., Hofman, A. (Albert), Teumer, A. (Alexander), Cox, A.J. (Amanda J.), Uitterlinden, A.G. (André), Wong, A. (Andrew), Smit, A.J. (Andries), Newman, A.B. (Anne B.), Britton, A.R., Ruusalepp, A. (Arno), Sennblad, B. (Bengt), Hedblad, B. (Bo), Pasaniuc, B. (Bogdan), Penninx, B.W.J.H. (Brenda), Langefeld, C.D. (Carl D.), Wassel, C.L. (Christina), Tzourio, C. (Christophe), Fava, C. (Cristiano), Baldassarre, D. (Damiano), O’Leary, D.H. (Daniel H.), Teupser, D. (Daniel), Kuh, D. (Diana), Tremoli, E. (Elena), Mannarino, E. (Elmo), Grossi, E. (Enzo), Boerwinkle, E.A. (Eric), Schadt, E.E. (Eric E.), Ingelsson, E. (Erik), Veglia, F. (Fabrizio), Rivadeneira Ramirez, F. (Fernando), Beutner, F. (Frank), Chauhan, G. (Ganesh), Heiss, G. (Gerardo), Snieder, H. (Harold), Campbell, H. (Harry), Völzke, H. (Henry), Markus, H.S. (Hugh), Deary, I.J. (Ian), Jukema, J.W. (Jan Wouter), Graaf, J. (Jacqueline) de, Price, J. (Jacqueline), Pott, J. (Janne), Hopewell, J., Liang, J. (Jingjing), Thiery, J.P. (Joachim), Engmann, J. (Jorgen), Gertow, K. (Karl), Rice, K.M. (Kenneth), Taylor, K.D. (Kent), Dhana, K. (Klodian), Kiemeney, L.A.L.M. (Lambertus A. L. M.), Kao, W.H.L. (Wen), Raffield, L.M. (Laura M.), Launer, L.J. (Lenore), Holdt, L.M. (Lesca), Dörr, M. (Marcus), Kubisch, C. (Christian), Traylor, M. (Matthew), Sitzer, M. (Matthias), Kumari, M. (Meena), Kivimaki, M. (Mika), Nalls, M.A. (Michael), Melander, O. (Olle), Raitakari, O. (Olli), Franco, O.H. (Oscar), Rueda-Ochoa, O.L. (Oscar), Roussos, A. (Alexandra), Whincup, P.H. (Peter), Amouyel, P. (Philippe), Giral, P. (Philippe), Anugu, P. (Pramod), Wong, Q. (Quenna), Malik, R. (Rainer), Rauramaa, R. (Rainer), Burkhardt, R. (Ralph), Hardy, R. (Rebecca), Schmidt, R. (Reinhold), Mutsert, R. (Reneé) de, Strawbridge, R.J. (Rona), Wannamethee, S.G. (Goya), Hägg, S. (Sara), Shah, S. (Sonia), McLachlan, S. (Stela), Trompet, S. (Stella), Seshadri, S. (Sudha), Kurl, S. (Sudhir), Heckbert, S.R. (Susan), Ring, S.M. (Susan), Harris, T.B. (Tamara B.), Lehtimäki, T. (Terho), Galesloot, T.E. (Tessel), Shah, T. (Tina), Faire, U. (Ulf) de, Plagnol, V. (Vincent), Rosamond, W.D. (Wayne), Post, W.S. (Wendy S.), Zhu, X. (Xiaofeng), Zhang, X. (Xiaoling), Guo, X. (Xiuqing), Saba, Y. (Yasaman), Okada, Y. (Yukinori), Mishra, A. (Aniket), Rutten-Jacobs, L. (Loes), Giese, A.-K. (Anne-Katrin), van der Laan, S.W. (Sander W.), Gretarsdottir, S. (Solveig), Anderson, C.D. (Christopher D.), Chong, M. (Michael), Adams, H.H.H. (Hieab), Ago, T. (Tetsuro), Almgren, P. (Peter), Ay, H. (Hakan), Bartz, T.M. (Traci M.), Benavente, O.R. (Oscar R.), Bevan, S. (Steve), Boncoraglio, G. (Giorgio Battista), Brown, R.D. (Robert D.), Butterworth, A.S. (Adam S.), Carrera, C. (Caty), Carty, C.L. (Cara L.), Chasman, D.I. (Daniel), Chen, W-M., Cole, J.W. (John W.), Cotlarciuc, I. (Ioana), Cruchaga, C. (Carlos), Danesh, J. (John), Bakker, P.I.W. (Paul) de, DeStefano, A.L. (Anita), Hoed, M. (Marcel) den, Duan, Q. (Qing), Engelter, S.T. (Stefan), Falcone, G.J. (Guido J.), Gottesman, R.F. (Rebecca), Grewal, R.P. (Raji P.), Gustafsson, S. (Stefan), Haessler, J. (Jeff), Harris, T.B. (Tamara), Hassan, A. (Ahamad), Havulinna, A.S. (Aki), Holliday, E.G. (Elizabeth), Howard, G. (George), Hsu, F.-C. (Fang-Chi), Hyacinth, H.I. (Hyacinth I.), Ikram, M.A. (Arfan), Irvin, M.R. (Marguerite R.), Jian, X. (Xueqiu), Jimenez-Conde, J. (Jordi), Johnson, J.A. (Julie A.), Jukema, J.W. (J. Wouter), Kanai, M. (Masahiro), Keene, K.L. (Keith), Kissela, B.M. (Brett M.), Kleindorfer, D.O. (Dawn O.), Kooperberg, C. (Charles), Kubo, M. (Michiaki), Lange, L.A. (Leslie), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Lee, J.-M. (Jin-Moo), Lemmens, R. (Robin), Leys, D. (Didier), Lewis, C.M. (Cathryn), Lin, W.-Y. (Wei-Yu), Lindgren, A.G. (Arne G.), Lorentzen, E. (Erik), Magnusson, P.K. (Patrik), Maguire, J.M. (Jane), Manichaikul, A. (Ani), McArdle, P.F. (Patrick), Meschia, J.F. (James F.), Mosley, T.H. (Thomas H.), Ninomiya, T. (Toshiharu), O’Donnell, M.J. (Martin J.), Pulit, S.L. (Sara), Rannikmäe, K. (Kristiina), Reiner, A.P. (Alexander P.), Rexrode, K. (Kathryn), Rich, S.S. (Stephen), Ridker, P.M. (Paul), Rost, N.S. (Natalia), Rothwell, P.M. (Peter), Rundek, T. (Tatjana), Muir, K.W. (Keith), Sakaue, S. (Saori), Sale, M.M. (Michele M.), Salomaa, V. (Veikko), Sapkota, B.R. (Bishwa R.), Schmidt, C.O. (Carsten O.), Sharma, P. (Pankaj), Slowik, A. (Agnieszka), Sudlow, C. (Cathie), Tanislav, C. (Christian), Tatlisumak, T. (Turgut), Thijs, V. (Vincent), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Tiedt, S. (Steffen), Walters, M. (Matthew), Wareham, N.J. (Nick), Wassertheil-Smoller, S. (Sylvia), Wiggins, K.L. (Kerri), Yang, Q. (Qiong Fang), Yusuf, S. (Salim), Pastinen, T. (Tomi), Schadt, E.E. (Eric), Koplev, S. (Simon), Codoni, V. (Veronica), Civelek, M. (Mete), Smith, N.L. (Nicholas), Tregouet, D.-A. (David-Alexandre), Christophersen, I.E. (Ingrid E.), Roselli, C. (Carolina), Lubitz, S.A. (Steven A.), Ellinor, P.T. (Patrick), Tai, E.S. (E. Shyong), Kooner, J.S. (Jaspal S.), Kato, N. (Norihiro), He, J. (Jiang), Harst, P. (Pim) van der, Elliott, P. (Paul), Chambers, J.C. (John C.), Takeuchi, F. (Fumihiko), Johnson, A.D. (Andrew), Sanghera, D.K. (Dharambir K.), Jern, C. (Christina), Strbian, D. (Daniel), Fernandez-Cadenas, I. (Israel), Longstreth Jr, W.T., Rolfs, A. (Arndt), Hata, J. (Jun), Woo, D. (Daniel), Rosand, J. (Jonathan), Pare, G. (Guillame), Saleheen, D. (Danish), Zwart, J-A. (John-Anker), Worrall, B.B. (Bradford B.), Kittner, T. (Thomas), Howson, J.M.M. (Joanna M. M.), Kamatani, Y. (Yoichiro), Dehghan, A. (Abbas), Seldenrijk, K.A. (Kees), Morrison, A.C. (Alanna), Hamsten, A. (Anders), Psaty, B.M. (Bruce), Duijn, C.M. (Cornelia) van, Lawlor, D.A. (Debbie), Mook-Kanamori, D.O. (Dennis O.), Bowden, D.W. (Donald), Schmidt, H. (Helena), Wilson, J.F. (James F.), Wilson, J.F. (James), Rotter, J.I. (Jerome I.), Wardlaw, J.M. (J.), Deanfield, J. (John), Halcox, J. (Julian), Lyytikäinen, L.-P. (Leo-Pekka), Loeffler, M. (Markus), Evans, M.K. (Michele), Debette, S. (Stéphanie), Humphries, S.E. (Steve), Völker, U. (Uwe), Gudnason, V. (Vilmundur), Hingorani, A. (Aroon), Björkegren, J.L.M. (Johan L.M.), Casas, J.P. (Juan), Ódonnell, C.J. (Christopher), Morris, R.W. (Richard), Franceschini, N. (Nora), Giambartolomei, C. (Claudia), Vries, P.S. (Paul) de, Finan, C. (Chris), Bis, J.C. (Joshua), Huntley, R.P. (Rachael P.), Lovering, R.C. (Ruth C.), Tajuddin, S.M. (Salman M.), Winkler, T.W. (Thomas W.), Graff, M. (Misa), Kavousi, M. (Maryam), Dale, C. (Caroline), Smith, A.V. (Albert), Hofer, E. (Edith), Leeuwen, E.M. (Elisa) van, Nolte, I.M. (Ilja), Lu, L. (Lingyi), Scholz, M. (Markus), Sargurupremraj, M. (Muralidharan), Pitkanen, N. (Niina), Franzén, O. (Oscar), Joshi, P.K. (Peter), Noordam, R. (Raymond), Marioni, R.E. (Riccardo), Hwang, S.-J. (Shih-Jen), Musani, S.K. (Solomon K.), Schminke, U. (Ulf), Palmas, W. (Walter), Isaacs, A.J. (Aaron), Correa, D.D., Zonderman, A.B., Hofman, A. (Albert), Teumer, A. (Alexander), Cox, A.J. (Amanda J.), Uitterlinden, A.G. (André), Wong, A. (Andrew), Smit, A.J. (Andries), Newman, A.B. (Anne B.), Britton, A.R., Ruusalepp, A. (Arno), Sennblad, B. (Bengt), Hedblad, B. (Bo), Pasaniuc, B. (Bogdan), Penninx, B.W.J.H. (Brenda), Langefeld, C.D. (Carl D.), Wassel, C.L. (Christina), Tzourio, C. (Christophe), Fava, C. (Cristiano), Baldassarre, D. (Damiano), O’Leary, D.H. (Daniel H.), Teupser, D. (Daniel), Kuh, D. (Diana), Tremoli, E. (Elena), Mannarino, E. (Elmo), Grossi, E. (Enzo), Boerwinkle, E.A. (Eric), Schadt, E.E. (Eric E.), Ingelsson, E. (Erik), Veglia, F. (Fabrizio), Rivadeneira Ramirez, F. (Fernando), Beutner, F. (Frank), Chauhan, G. (Ganesh), Heiss, G. (Gerardo), Snieder, H. (Harold), Campbell, H. (Harry), Völzke, H. (Henry), Markus, H.S. (Hugh), Deary, I.J. (Ian), Jukema, J.W. (Jan Wouter), Graaf, J. (Jacqueline) de, Price, J. (Jacqueline), Pott, J. (Janne), Hopewell, J., Liang, J. (Jingjing), Thiery, J.P. (Joachim), Engmann, J. (Jorgen), Gertow, K. (Karl), Rice, K.M. (Kenneth), Taylor, K.D. (Kent), Dhana, K. (Klodian), Kiemeney, L.A.L.M. (Lambertus A. L. M.), Kao, W.H.L. (Wen), Raffield, L.M. (Laura M.), Launer, L.J. (Lenore), Holdt, L.M. (Lesca), Dörr, M. (Marcus), Kubisch, C. (Christian), Traylor, M. (Matthew), Sitzer, M. (Matthias), Kumari, M. (Meena), Kivimaki, M. (Mika), Nalls, M.A. (Michael), Melander, O. (Olle), Raitakari, O. (Olli), Franco, O.H. (Oscar), Rueda-Ochoa, O.L. (Oscar), Roussos, A. (Alexandra), Whincup, P.H. (Peter), Amouyel, P. (Philippe), Giral, P. (Philippe), Anugu, P. (Pramod), Wong, Q. (Quenna), Malik, R. (Rainer), Rauramaa, R. (Rainer), Burkhardt, R. (Ralph), Hardy, R. (Rebecca), Schmidt, R. (Reinhold), Mutsert, R. (Reneé) de, Strawbridge, R.J. (Rona), Wannamethee, S.G. (Goya), Hägg, S. (Sara), Shah, S. (Sonia), McLachlan, S. (Stela), Trompet, S. (Stella), Seshadri, S. (Sudha), Kurl, S. (Sudhir), Heckbert, S.R. (Susan), Ring, S.M. (Susan), Harris, T.B. (Tamara B.), Lehtimäki, T. (Terho), Galesloot, T.E. (Tessel), Shah, T. (Tina), Faire, U. (Ulf) de, Plagnol, V. (Vincent), Rosamond, W.D. (Wayne), Post, W.S. (Wendy S.), Zhu, X. (Xiaofeng), Zhang, X. (Xiaoling), Guo, X. (Xiuqing), Saba, Y. (Yasaman), Okada, Y. (Yukinori), Mishra, A. (Aniket), Rutten-Jacobs, L. (Loes), Giese, A.-K. (Anne-Katrin), van der Laan, S.W. (Sander W.), Gretarsdottir, S. (Solveig), Anderson, C.D. (Christopher D.), Chong, M. (Michael), Adams, H.H.H. (Hieab), Ago, T. (Tetsuro), Almgren, P. (Peter), Ay, H. (Hakan), Bartz, T.M. (Traci M.), Benavente, O.R. (Oscar R.), Bevan, S. (Steve), Boncoraglio, G. (Giorgio Battista), Brown, R.D. (Robert D.), Butterworth, A.S. (Adam S.), Carrera, C. (Caty), Carty, C.L. (Cara L.), Chasman, D.I. (Daniel), Chen, W-M., Cole, J.W. (John W.), Cotlarciuc, I. (Ioana), Cruchaga, C. (Carlos), Danesh, J. (John), Bakker, P.I.W. (Paul) de, DeStefano, A.L. (Anita), Hoed, M. (Marcel) den, Duan, Q. (Qing), Engelter, S.T. (Stefan), Falcone, G.J. (Guido J.), Gottesman, R.F. (Rebecca), Grewal, R.P. (Raji P.), Gustafsson, S. (Stefan), Haessler, J. (Jeff), Harris, T.B. (Tamara), Hassan, A. (Ahamad), Havulinna, A.S. (Aki), Holliday, E.G. (Elizabeth), Howard, G. (George), Hsu, F.-C. (Fang-Chi), Hyacinth, H.I. (Hyacinth I.), Ikram, M.A. (Arfan), Irvin, M.R. (Marguerite R.), Jian, X. (Xueqiu), Jimenez-Conde, J. (Jordi), Johnson, J.A. (Julie A.), Jukema, J.W. (J. Wouter), Kanai, M. (Masahiro), Keene, K.L. (Keith), Kissela, B.M. (Brett M.), Kleindorfer, D.O. (Dawn O.), Kooperberg, C. (Charles), Kubo, M. (Michiaki), Lange, L.A. (Leslie), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Lee, J.-M. (Jin-Moo), Lemmens, R. (Robin), Leys, D. (Didier), Lewis, C.M. (Cathryn), Lin, W.-Y. (Wei-Yu), Lindgren, A.G. (Arne G.), Lorentzen, E. (Erik), Magnusson, P.K. (Patrik), Maguire, J.M. (Jane), Manichaikul, A. (Ani), McArdle, P.F. (Patrick), Meschia, J.F. (James F.), Mosley, T.H. (Thomas H.), Ninomiya, T. (Toshiharu), O’Donnell, M.J. (Martin J.), Pulit, S.L. (Sara), Rannikmäe, K. (Kristiina), Reiner, A.P. (Alexander P.), Rexrode, K. (Kathryn), Rich, S.S. (Stephen), Ridker, P.M. (Paul), Rost, N.S. (Natalia), Rothwell, P.M. (Peter), Rundek, T. (Tatjana), Muir, K.W. (Keith), Sakaue, S. (Saori), Sale, M.M. (Michele M.), Salomaa, V. (Veikko), Sapkota, B.R. (Bishwa R.), Schmidt, C.O. (Carsten O.), Sharma, P. (Pankaj), Slowik, A. (Agnieszka), Sudlow, C. (Cathie), Tanislav, C. (Christian), Tatlisumak, T. (Turgut), Thijs, V. (Vincent), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Tiedt, S. (Steffen), Walters, M. (Matthew), Wareham, N.J. (Nick), Wassertheil-Smoller, S. (Sylvia), Wiggins, K.L. (Kerri), Yang, Q. (Qiong Fang), Yusuf, S. (Salim), Pastinen, T. (Tomi), Schadt, E.E. (Eric), Koplev, S. (Simon), Codoni, V. (Veronica), Civelek, M. (Mete), Smith, N.L. (Nicholas), Tregouet, D.-A. (David-Alexandre), Christophersen, I.E. (Ingrid E.), Roselli, C. (Carolina), Lubitz, S.A. (Steven A.), Ellinor, P.T. (Patrick), Tai, E.S. (E. Shyong), Kooner, J.S. (Jaspal S.), Kato, N. (Norihiro), He, J. (Jiang), Harst, P. (Pim) van der, Elliott, P. (Paul), Chambers, J.C. (John C.), Takeuchi, F. (Fumihiko), Johnson, A.D. (Andrew), Sanghera, D.K. (Dharambir K.), Jern, C. (Christina), Strbian, D. (Daniel), Fernandez-Cadenas, I. (Israel), Longstreth Jr, W.T., Rolfs, A. (Arndt), Hata, J. (Jun), Woo, D. (Daniel), Rosand, J. (Jonathan), Pare, G. (Guillame), Saleheen, D. (Danish), Zwart, J-A. (John-Anker), Worrall, B.B. (Bradford B.), Kittner, T. (Thomas), Howson, J.M.M. (Joanna M. M.), Kamatani, Y. (Yoichiro), Dehghan, A. (Abbas), Seldenrijk, K.A. (Kees), Morrison, A.C. (Alanna), Hamsten, A. (Anders), Psaty, B.M. (Bruce), Duijn, C.M. (Cornelia) van, Lawlor, D.A. (Debbie), Mook-Kanamori, D.O. (Dennis O.), Bowden, D.W. (Donald), Schmidt, H. (Helena), Wilson, J.F. (James F.), Wilson, J.F. (James), Rotter, J.I. (Jerome I.), Wardlaw, J.M. (J.), Deanfield, J. (John), Halcox, J. (Julian), Lyytikäinen, L.-P. (Leo-Pekka), Loeffler, M. (Markus), Evans, M.K. (Michele), Debette, S. (Stéphanie), Humphries, S.E. (Steve), Völker, U. (Uwe), Gudnason, V. (Vilmundur), Hingorani, A. (Aroon), Björkegren, J.L.M. (Johan L.M.), Casas, J.P. (Juan), Ódonnell, C.J. (Christopher), and Morris, R.W. (Richard)
Abstract: Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.
Published: 2018
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6. PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity

Author: Setten, J. (Jessica) van, Brody, J.A. (Jennifer A.), Jamshidi, Y. (Yalda), Swenson, B.R. (Brenton R.), Butler, A.M. (Anne M.), Campbell, H. (Harry), Del Greco, F.M. (Fabiola), Evans, D.S. (Daniel), Gibson, Q. (Quince), Gudbjartsson, D.F. (Daniel), Kerr, K.F. (Kathleen), Krijthe, B.P. (Bouwe), Lyytikäinen, L.-P. (Leo-Pekka), Müller, C. (Christian), Müller-Nurasyid, M. (Martina), Nolte, I.M. (Ilja), Padmanabhan, S. (Sandosh), Ritchie, M.D. (Marylyn D.), Robino, A. (Antonietta), Smith, A.V. (Albert), Steri, M. (Maristella), Tanaka, T. (Toshiko), Teumer, A. (Alexander), Trompet, S. (Stella), Ulivi, S. (Sheila), Verweij, N. (Niek), Yin, X. (Xiaoyan), Arnar, D.O. (David O.), Asselbergs, F.W. (Folkert W.), Bader, J.S. (Joel), Barnard, J. (John), Bis, J.C. (Joshua), Blankenberg, S. (Stefan), Boerwinkle, E. (Eric), Bradford, Y. (Yuki), Buckley, B.M. (Brendan M.), Chung, M.K. (Mina), Crawford, D. (Dana), Hoed, M. (Marcel) den, Denny, J.C. (Joshua C.), Dominiczak, A. (Anna), Ehret, G.B. (Georg B.), Eijgelsheim, M. (Mark), Ellinor, P.T. (Patrick), Felix, S.B. (Stephan), Franco, O.H. (Oscar), Franke, L. (Lude), Harris, T.B. (Tamara), Holm, H. (Hilma), Ilaria, G. (Gandin), Iorio, A. (Annamaria), Kähönen, M. (Mika), Kolcic, I. (Ivana), Kors, J.A. (Jan), Lakatta, E. (Edward), Launer, L.J. (Lenore), Lin, H. (Honghuang), Lin, H.J. (Henry J.), Loos, R.J.F. (Ruth), Lubitz, S.A. (Steven A.), MacFarlane, P.W. (Peter), Magnani, J.W. (Jared), Leach, I.M. (Irene Mateo), Meitinger, T. (Thomas), Mitchell, B.D. (Braxton), Munzel, T. (Thomas), Papanicolaou, G.J. (George J.), Peters, A. (Annette), Pfeufer, A. (Arne), Pramstaller, P.P. (Peter Paul), Raitakari, O. (Olli), Rotter, J.I. (Jerome I.), Rudan, I. (Igor), Samani, N.J. (Nilesh J.), Schlessinger, D. (David), Silva Aldana, C.T. (Claudia), Sinner, M.F. (Moritz), Smith, J.D. (Jonathan), Snieder, H. (Harold), Soliman, E.Z. (Elsayed Z.), Spector, T.D. (Timothy), Stott, D.J. (David. J.), Strauch, K. (Konstantin), Tarasov, K.V. (Kirill V.), Thorsteinsdottir, U. (Unnur), Uitterlinden, A.G. (André), Wagoner, D.R. (David) van, Völker, U. (Uwe), Völzke, H. (Henry), Waldenberger, M. (Melanie), Jan Westra, H. (Harm), Wild, P.S. (Philipp), Zeller, T. (Tanja), Alonso, A. (Alvaro), Avery, C.L., Bandinelli, S. (Stefania), Benjamin, E.J. (Emelia), Cucca, F. (Francesco), Dörr, M. (Marcus), Ferrucci, L. (Luigi), Gasparini, P. (Paolo), Gudnason, V. (Vilmundur), Hayward, C. (Caroline), Heckbert, S.R. (Susan), Hicks, A.A. (Andrew A.), Jukema, J.W. (Jan Wouter), Kääb, S. (Stefan), Lehtimäki, T. (Terho), Liu, Y. (YongMei), Munroe, P. (Patricia), Parsa, A. (Afshin), Polasek, O. (Ozren), Psaty, B.M. (Bruce M.), Roden, D.M. (Dan), Schnabel, R.B. (Renate), Sinagra, G. (Gianfranco), Zwart, J-A. (John-Anker), Stricker, B.H.Ch. (Bruno), van der Harst, P. (Pim), Duijn, C.M. (Cornelia) van, Wilson, J.F. (James F.), Gharib, S.A. (Sina), Bakker, P.I.W. (Paul) de, Isaacs, A. (Aaron), Arking, D.E. (Dan), Sotoodehnia, N. (Nona), Setten, J. (Jessica) van, Brody, J.A. (Jennifer A.), Jamshidi, Y. (Yalda), Swenson, B.R. (Brenton R.), Butler, A.M. (Anne M.), Campbell, H. (Harry), Del Greco, F.M. (Fabiola), Evans, D.S. (Daniel), Gibson, Q. (Quince), Gudbjartsson, D.F. (Daniel), Kerr, K.F. (Kathleen), Krijthe, B.P. (Bouwe), Lyytikäinen, L.-P. (Leo-Pekka), Müller, C. (Christian), Müller-Nurasyid, M. (Martina), Nolte, I.M. (Ilja), Padmanabhan, S. (Sandosh), Ritchie, M.D. (Marylyn D.), Robino, A. (Antonietta), Smith, A.V. (Albert), Steri, M. (Maristella), Tanaka, T. (Toshiko), Teumer, A. (Alexander), Trompet, S. (Stella), Ulivi, S. (Sheila), Verweij, N. (Niek), Yin, X. (Xiaoyan), Arnar, D.O. (David O.), Asselbergs, F.W. (Folkert W.), Bader, J.S. (Joel), Barnard, J. (John), Bis, J.C. (Joshua), Blankenberg, S. (Stefan), Boerwinkle, E. (Eric), Bradford, Y. (Yuki), Buckley, B.M. (Brendan M.), Chung, M.K. (Mina), Crawford, D. (Dana), Hoed, M. (Marcel) den, Denny, J.C. (Joshua C.), Dominiczak, A. (Anna), Ehret, G.B. (Georg B.), Eijgelsheim, M. (Mark), Ellinor, P.T. (Patrick), Felix, S.B. (Stephan), Franco, O.H. (Oscar), Franke, L. (Lude), Harris, T.B. (Tamara), Holm, H. (Hilma), Ilaria, G. (Gandin), Iorio, A. (Annamaria), Kähönen, M. (Mika), Kolcic, I. (Ivana), Kors, J.A. (Jan), Lakatta, E. (Edward), Launer, L.J. (Lenore), Lin, H. (Honghuang), Lin, H.J. (Henry J.), Loos, R.J.F. (Ruth), Lubitz, S.A. (Steven A.), MacFarlane, P.W. (Peter), Magnani, J.W. (Jared), Leach, I.M. (Irene Mateo), Meitinger, T. (Thomas), Mitchell, B.D. (Braxton), Munzel, T. (Thomas), Papanicolaou, G.J. (George J.), Peters, A. (Annette), Pfeufer, A. (Arne), Pramstaller, P.P. (Peter Paul), Raitakari, O. (Olli), Rotter, J.I. (Jerome I.), Rudan, I. (Igor), Samani, N.J. (Nilesh J.), Schlessinger, D. (David), Silva Aldana, C.T. (Claudia), Sinner, M.F. (Moritz), Smith, J.D. (Jonathan), Snieder, H. (Harold), Soliman, E.Z. (Elsayed Z.), Spector, T.D. (Timothy), Stott, D.J. (David. J.), Strauch, K. (Konstantin), Tarasov, K.V. (Kirill V.), Thorsteinsdottir, U. (Unnur), Uitterlinden, A.G. (André), Wagoner, D.R. (David) van, Völker, U. (Uwe), Völzke, H. (Henry), Waldenberger, M. (Melanie), Jan Westra, H. (Harm), Wild, P.S. (Philipp), Zeller, T. (Tanja), Alonso, A. (Alvaro), Avery, C.L., Bandinelli, S. (Stefania), Benjamin, E.J. (Emelia), Cucca, F. (Francesco), Dörr, M. (Marcus), Ferrucci, L. (Luigi), Gasparini, P. (Paolo), Gudnason, V. (Vilmundur), Hayward, C. (Caroline), Heckbert, S.R. (Susan), Hicks, A.A. (Andrew A.), Jukema, J.W. (Jan Wouter), Kääb, S. (Stefan), Lehtimäki, T. (Terho), Liu, Y. (YongMei), Munroe, P. (Patricia), Parsa, A. (Afshin), Polasek, O. (Ozren), Psaty, B.M. (Bruce M.), Roden, D.M. (Dan), Schnabel, R.B. (Renate), Sinagra, G. (Gianfranco), Zwart, J-A. (John-Anker), Stricker, B.H.Ch. (Bruno), van der Harst, P. (Pim), Duijn, C.M. (Cornelia) van, Wilson, J.F. (James F.), Gharib, S.A. (Sina), Bakker, P.I.W. (Paul) de, Isaacs, A. (Aaron), Arking, D.E. (Dan), and Sotoodehnia, N. (Nona)
Abstract: Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genome-wide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are over-represented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of ~105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ion-channel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development.
Published: 2018
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7. Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function

Author: Wyss, A.B. (Annah B.), Sofer, T. (Tamar), Lee, M.K. (Mi Kyeong), Terzikhan, N. (Natalie), Nguyen, J.N. (Jennifer N.), Lahousse, L. (Lies), Latourelle, J.C. (Jeanne), Smith, A.V. (Albert), Bartz, T.M. (Traci M.), Feitosa, M.F. (Mary Furlan), Gao, W. (Wei), Ahluwalia, T.S. (Tarunveer Singh), Tang, W. (Wenbo), Oldmeadow, C. (Christopher), Duan, Q. (Qing), Jong, K. (Kim) de, Wojczynski, M.K. (Mary ), Wang, X.-Q. (Xin-Qun), Noordam, R. (Raymond), Hartwig, F.P. (Fernando Pires), Jackson, V.E. (Victoria E.), Wang, T. (Tianyuan), Obeidat, M. (Ma’en), Hobbs, B.D. (Brian D.), Huan, T. (Tianxiao), Gui, H. (Hongsheng), Parker, M.M. (Margaret M.), Hu, D. (Donglei), Mogil, L.S. (Lauren S.), Kichaev, G. (Gleb), Jin, J. (Jianping), Graff, M.J. (Maud J.L.), Harris, T.B. (Tamara), Kalhan, R. (Ravi), Heckbert, S.R. (Susan), Paternoster, L. (Lavinia), Burkart, K.M. (Kristin), Liu, Y. (YongMei), Holliday, E.G. (Elizabeth), Wilson, J.F. (James), Vonk, J.M. (Judith), Sanders, J.L. (Jason L.), Barr, R.G. (Graham), Mutsert, R. (Reneé) de, Menezes, A.M.B. (Ana Maria Baptista), Adams, H.H.H. (Hieab), Van Den Berge, M. (Maarten), Joehanes, R. (Roby), Levin, A.M. (Albert M.), Liberto, J. (Jennifer), Launer, L.J. (Lenore), Morrison, A.C. (Alanna), Sitlani, C.M. (Colleen), Celedón, J.C. (Juan C.), Kritchevsky, S.B. (Stephen), Scott, R.J. (Rodney J.), Christensen, K. (Kaare), Rotter, J.I. (Jerome I.), Bonten, T.N. (Tobias N.), Wehrmeister, F.C. (Fernando C.), Bossé, Y. (Yohan), Xiao, S. (Shujie), Oh, S. (Sam), Franceschini, N. (Nora), Brody, J.A. (Jennifer A.), Kaplan, R.C. (Robert), Lohman, K. (Kurt), McEvoy, M. (Mark), Province, M.A. (Mike), Rosendaal, F.R. (Frits), Taylor, K.D. (Kent), Nickle, D.C. (David C.), Williams, L.K. (L. Keoki), Burchard, E.G. (Esteban), Wheeler, H.E. (Heather), Sin, D.D. (Don D.), Gudnason, V. (Vilmundur), North, K.E. (Kari), Fornage, M. (Myriam), Psaty, B.M. (Bruce M.), Myers, R.H. (Richard), O’Connor, G. (George), Hansen, T. (Torben), Laurie, C.C. (Cathy C.), Cassano, P.A. (Patricia), Sung, J. (Joohon), Kim, W.J. (Woo Jin), Attia, J. (John), Lange, L.A. (Leslie), Boezen, H.M. (Marike), Thyagarajan, B. (Bharat), Rich, S.S. (Stephen), Mook-Kanamori, D.O. (Dennis O.), Horta, B.L. (Bernardo Lessa), Uitterlinden, A.G. (André), Im, H.K. (Hae Kyung), Cho, M.H. (Michael H.), Brusselle, G.G. (Guy), Gharib, S.A. (Sina), Dupuis, J. (Josée), Manichaikul, A. (Ani), London, S.J. (Stephanie J.), Wyss, A.B. (Annah B.), Sofer, T. (Tamar), Lee, M.K. (Mi Kyeong), Terzikhan, N. (Natalie), Nguyen, J.N. (Jennifer N.), Lahousse, L. (Lies), Latourelle, J.C. (Jeanne), Smith, A.V. (Albert), Bartz, T.M. (Traci M.), Feitosa, M.F. (Mary Furlan), Gao, W. (Wei), Ahluwalia, T.S. (Tarunveer Singh), Tang, W. (Wenbo), Oldmeadow, C. (Christopher), Duan, Q. (Qing), Jong, K. (Kim) de, Wojczynski, M.K. (Mary ), Wang, X.-Q. (Xin-Qun), Noordam, R. (Raymond), Hartwig, F.P. (Fernando Pires), Jackson, V.E. (Victoria E.), Wang, T. (Tianyuan), Obeidat, M. (Ma’en), Hobbs, B.D. (Brian D.), Huan, T. (Tianxiao), Gui, H. (Hongsheng), Parker, M.M. (Margaret M.), Hu, D. (Donglei), Mogil, L.S. (Lauren S.), Kichaev, G. (Gleb), Jin, J. (Jianping), Graff, M.J. (Maud J.L.), Harris, T.B. (Tamara), Kalhan, R. (Ravi), Heckbert, S.R. (Susan), Paternoster, L. (Lavinia), Burkart, K.M. (Kristin), Liu, Y. (YongMei), Holliday, E.G. (Elizabeth), Wilson, J.F. (James), Vonk, J.M. (Judith), Sanders, J.L. (Jason L.), Barr, R.G. (Graham), Mutsert, R. (Reneé) de, Menezes, A.M.B. (Ana Maria Baptista), Adams, H.H.H. (Hieab), Van Den Berge, M. (Maarten), Joehanes, R. (Roby), Levin, A.M. (Albert M.), Liberto, J. (Jennifer), Launer, L.J. (Lenore), Morrison, A.C. (Alanna), Sitlani, C.M. (Colleen), Celedón, J.C. (Juan C.), Kritchevsky, S.B. (Stephen), Scott, R.J. (Rodney J.), Christensen, K. (Kaare), Rotter, J.I. (Jerome I.), Bonten, T.N. (Tobias N.), Wehrmeister, F.C. (Fernando C.), Bossé, Y. (Yohan), Xiao, S. (Shujie), Oh, S. (Sam), Franceschini, N. (Nora), Brody, J.A. (Jennifer A.), Kaplan, R.C. (Robert), Lohman, K. (Kurt), McEvoy, M. (Mark), Province, M.A. (Mike), Rosendaal, F.R. (Frits), Taylor, K.D. (Kent), Nickle, D.C. (David C.), Williams, L.K. (L. Keoki), Burchard, E.G. (Esteban), Wheeler, H.E. (Heather), Sin, D.D. (Don D.), Gudnason, V. (Vilmundur), North, K.E. (Kari), Fornage, M. (Myriam), Psaty, B.M. (Bruce M.), Myers, R.H. (Richard), O’Connor, G. (George), Hansen, T. (Torben), Laurie, C.C. (Cathy C.), Cassano, P.A. (Patricia), Sung, J. (Joohon), Kim, W.J. (Woo Jin), Attia, J. (John), Lange, L.A. (Leslie), Boezen, H.M. (Marike), Thyagarajan, B. (Bharat), Rich, S.S. (Stephen), Mook-Kanamori, D.O. (Dennis O.), Horta, B.L. (Bernardo Lessa), Uitterlinden, A.G. (André), Im, H.K. (Hae Kyung), Cho, M.H. (Michael H.), Brusselle, G.G. (Guy), Gharib, S.A. (Sina), Dupuis, J. (Josée), Manichaikul, A. (Ani), and London, S.J. (Stephanie J.)
Abstract: Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of lu
Published: 2018
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8. Exome-chip meta-analysis identifies novel loci associated with cardiac conduction, including ADAMTS6

Author: Prins, B.P. (Bram P.), Mead, T.J. (Timothy J.), Brody, J.A. (Jennifer A.), Sveinbjornsson, G. (Gardar), Ntalla, I. (Ioanna), Bihlmeyer, N.A. (Nathan A.), Berg, M.E. (Marten) van den, Bork-Jensen, J. (Jette), Cappellani, S. (Stefania), Van Duijvenboden, S. (Stefan), Klena, N.T. (Nikolai T.), Gabriel, G.C. (George C.), Liu, X. (Xiaoqin), Gulec, C. (Cagri), Grarup, N. (Niels), Haessler, J. (Jeff), Hall, L.M. (Leanne M.), Iorio, A. (Annamaria), Isaacs, A. (Aaron), Li-Gao, R. (Ruifang), Lin, H. (Honghuang), Liu, C.-T. (Ching-Ti), Lyytikäinen, L.-P. (Leo-Pekka), Marten, J. (Jonathan), Mei, H. (Hao), Müller-Nurasyid, M. (Martina), Orini, M. (Michele), Padmanabhan, S. (Sandosh), Radmanesh, F. (Farid), Ramirez, J. (Julia), Robino, A. (Antonietta), Schwartz, M. (Molly), Setten, J. (Jessica) van, Smith, A.V. (Albert), Verweij, N. (Niek), Warren, H. (Helen), Weiss, S. (Stefan), Alonso, A. (Alvaro), Arnar, D.O. (David O.), Bots, M.L. (Michiel), Boer, R.A. (Rudolf) de, Dominiczak, A. (Anna), Eijgelsheim, M. (Mark), Ellinor, P.T. (Patrick), Guo, X. (Xiuqing), Felix, S.B. (Stephan), Harris, T.B. (Tamara), Hayward, C. (Caroline), Heckbert, S.R. (Susan), Huang, P.L. (Paul L.), Jukema, J.W. (Jan Wouter), Kähönen, M. (Mika), Kors, J.A. (Jan), Lambiase, P.D. (Pier), Launer, L.J. (Lenore), Li, M. (Man), Linneberg, A. (Allan), Nelson, C.P. (Christopher P.), Pedersen, O. (Oluf), Perez, M. (Marco), Peters, A. (Annette), Polasek, O. (Ozren), Psaty, B.M. (Bruce M.), Raitakari, O. (Olli), Rice, K.M. (Kenneth), Rotter, J.I. (Jerome I.), Sinner, M.F. (Moritz), Soliman, E.Z. (Elsayed Z.), Spector, T.D. (Timothy), Strauch, K. (Konstantin), Thorsteinsdottir, U. (Unnur), Tinker, A. (Andrew), Trompet, S. (Stella), Uitterlinden, A.G. (André), Vaartjes, I. (Ilonca), Meer, P. (Peter) van der, Völker, U. (Uwe), Völzke, H. (Henry), Waldenberger, M. (Melanie), Wilson, J.F. (James), Xie, Z. (Zhijun), Asselbergs, F.W. (Folkert W.), Dörr, M. (Marcus), Duijn, C.M. (Cornelia) van, Gasparini, P. (Paolo), Gudbjartsson, D.F. (Daniel), Gudnason, V. (Vilmundur), Hansen, T. (Torben), Kääb, S. (Stefan), Kanters, J.K., Kooperberg, C. (Charles), Lehtimäki, T. (Terho), Lin, H.J. (Henry J.), Lubitz, S.A. (Steven A.), Mook-Kanamori, D.O. (Dennis O.), Conti, F.J. (Francesco J.), Newton-Cheh, C. (Christopher), Rosand, J. (Jonathan), Rudan, I. (Igor), Samani, N.J. (Nilesh J.), Sinagra, G. (Gianfranco), Smith, B.H. (Blair), Holm, H. (Hilma), Stricker, B.H.Ch. (Bruno), Ulivi, S. (Sheila), Sotoodehnia, N. (Nona), Apte, S.S. (Suneel S.), van der Harst, P. (Pim), Zwart, J-A. (John-Anker), Munroe, P. (Patricia), Arking, D.E. (Dan), Lo, C.W. (Cecilia W.), Jamshidi, Y. (Yalda), Prins, B.P. (Bram P.), Mead, T.J. (Timothy J.), Brody, J.A. (Jennifer A.), Sveinbjornsson, G. (Gardar), Ntalla, I. (Ioanna), Bihlmeyer, N.A. (Nathan A.), Berg, M.E. (Marten) van den, Bork-Jensen, J. (Jette), Cappellani, S. (Stefania), Van Duijvenboden, S. (Stefan), Klena, N.T. (Nikolai T.), Gabriel, G.C. (George C.), Liu, X. (Xiaoqin), Gulec, C. (Cagri), Grarup, N. (Niels), Haessler, J. (Jeff), Hall, L.M. (Leanne M.), Iorio, A. (Annamaria), Isaacs, A. (Aaron), Li-Gao, R. (Ruifang), Lin, H. (Honghuang), Liu, C.-T. (Ching-Ti), Lyytikäinen, L.-P. (Leo-Pekka), Marten, J. (Jonathan), Mei, H. (Hao), Müller-Nurasyid, M. (Martina), Orini, M. (Michele), Padmanabhan, S. (Sandosh), Radmanesh, F. (Farid), Ramirez, J. (Julia), Robino, A. (Antonietta), Schwartz, M. (Molly), Setten, J. (Jessica) van, Smith, A.V. (Albert), Verweij, N. (Niek), Warren, H. (Helen), Weiss, S. (Stefan), Alonso, A. (Alvaro), Arnar, D.O. (David O.), Bots, M.L. (Michiel), Boer, R.A. (Rudolf) de, Dominiczak, A. (Anna), Eijgelsheim, M. (Mark), Ellinor, P.T. (Patrick), Guo, X. (Xiuqing), Felix, S.B. (Stephan), Harris, T.B. (Tamara), Hayward, C. (Caroline), Heckbert, S.R. (Susan), Huang, P.L. (Paul L.), Jukema, J.W. (Jan Wouter), Kähönen, M. (Mika), Kors, J.A. (Jan), Lambiase, P.D. (Pier), Launer, L.J. (Lenore), Li, M. (Man), Linneberg, A. (Allan), Nelson, C.P. (Christopher P.), Pedersen, O. (Oluf), Perez, M. (Marco), Peters, A. (Annette), Polasek, O. (Ozren), Psaty, B.M. (Bruce M.), Raitakari, O. (Olli), Rice, K.M. (Kenneth), Rotter, J.I. (Jerome I.), Sinner, M.F. (Moritz), Soliman, E.Z. (Elsayed Z.), Spector, T.D. (Timothy), Strauch, K. (Konstantin), Thorsteinsdottir, U. (Unnur), Tinker, A. (Andrew), Trompet, S. (Stella), Uitterlinden, A.G. (André), Vaartjes, I. (Ilonca), Meer, P. (Peter) van der, Völker, U. (Uwe), Völzke, H. (Henry), Waldenberger, M. (Melanie), Wilson, J.F. (James), Xie, Z. (Zhijun), Asselbergs, F.W. (Folkert W.), Dörr, M. (Marcus), Duijn, C.M. (Cornelia) van, Gasparini, P. (Paolo), Gudbjartsson, D.F. (Daniel), Gudnason, V. (Vilmundur), Hansen, T. (Torben), Kääb, S. (Stefan), Kanters, J.K., Kooperberg, C. (Charles), Lehtimäki, T. (Terho), Lin, H.J. (Henry J.), Lubitz, S.A. (Steven A.), Mook-Kanamori, D.O. (Dennis O.), Conti, F.J. (Francesco J.), Newton-Cheh, C. (Christopher), Rosand, J. (Jonathan), Rudan, I. (Igor), Samani, N.J. (Nilesh J.), Sinagra, G. (Gianfranco), Smith, B.H. (Blair), Holm, H. (Hilma), Stricker, B.H.Ch. (Bruno), Ulivi, S. (Sheila), Sotoodehnia, N. (Nona), Apte, S.S. (Suneel S.), van der Harst, P. (Pim), Zwart, J-A. (John-Anker), Munroe, P. (Patricia), Arking, D.E. (Dan), Lo, C.W. (Cecilia W.), and Jamshidi, Y. (Yalda)
Abstract: Background: Genome-wide association studies conducted on QRS duration, an electrocardiographic measurement associated with heart failure and sudden cardiac death, have led to novel biological insights into cardiac function. However, the variants identified fall predominantly in non-coding regions and their underlying mechanisms remain unclear. Results: Here, we identify putative functional coding variation associated with changes in the QRS interval duration by combining Illumina HumanExome BeadChip genotype data from 77,898 participants of European ancestry and 7695 of African descent in our discovery cohort, followed by replication in 111,874 individuals of European ancestry from the UK Biobank and deCODE cohorts. We identify ten novel loci, seven within coding regions, including ADAMTS6, significantly associated with QRS duration in gene-based analyses. ADAMTS6 encodes a secreted metalloprotease of currently unknown function. In vitro validation analysis shows that the QRS-associated variants lead to impaired ADAMTS6 secretion and loss-of function analysis in mice demonstrates a previously unappreciated role for ADAMTS6 in connexin 43 gap junction expression, which is essential for myocardial conduction. Conclusions: Our approach identifies novel coding and non-coding variants underlying ventricular depolarization and provides a possible mechanism for the ADAMTS6-associated conduction changes.
Published: 2018
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9. Fifteen Genetic Loci Associated with the Electrocardiographic P Wave

Author: Christophersen, I.E. (Ingrid E.), Magnani, J.W. (Jared), Yin, X. (Xiaoyan), Barnard, J. (John), Weng, L.-C., Arking, D.E. (Dan E.), Niemeijer, M.N. (Maartje), Lubitz, S.A. (Steven), Avery, C.L., Duan, Q. (Qing), Felix, S.B. (Stephan B.), Bis, J.C. (Joshua), Kerr, K.F. (Kathleen), Isaacs, A.J. (Aaron), Müller-Nurasyid, M. (Martina), Müller, C. (Christian), North, K.E. (Kari), Reiner, A. (Alexander), Tinker, L.F. (Lesley F.), Kors, J.A. (Jan), Teumer, A. (Alexander), Petersmann, A. (Astrid), Sinner, M.F. (Moritz), Buzkova, P. (Petra), Smith, J.D. (Jonathan), Wagoner, D.R. (David) van, Völker, U. (Uwe), Waldenberger, M. (Melanie), Peters, A. (Annette), Meitinger, T. (Thomas), Limacher, M.C. (Marian C.), Wilhelmsen, K.C., Psaty, B.M. (Bruce M.), Hofman, A. (Albert), Uitterlinden, A.G. (André), Krijthe, B.P. (Bouwe P.), Zhang, Z. (Z.), Schnabel, R.B. (Renate), Kääb, S. (Stefan), Duijn, C.M. (Cornelia) van, Rotter, J.I. (Jerome I.), Sotoodehnia, N. (Nona), Dörr, M. (Marcus), Li, Y. (Yun), Chung, M.K. (Mina), Soliman, E.Z. (Elsayed Z.), Alonso, A. (Alvaro), Whitsel, E.A. (Eric), Stricker, B.H.Ch. (Bruno), Benjamin, E.J. (Emelia J.), Heckbert, S.R. (Susan), Ellinor, P.T. (Patrick), Christophersen, I.E. (Ingrid E.), Magnani, J.W. (Jared), Yin, X. (Xiaoyan), Barnard, J. (John), Weng, L.-C., Arking, D.E. (Dan E.), Niemeijer, M.N. (Maartje), Lubitz, S.A. (Steven), Avery, C.L., Duan, Q. (Qing), Felix, S.B. (Stephan B.), Bis, J.C. (Joshua), Kerr, K.F. (Kathleen), Isaacs, A.J. (Aaron), Müller-Nurasyid, M. (Martina), Müller, C. (Christian), North, K.E. (Kari), Reiner, A. (Alexander), Tinker, L.F. (Lesley F.), Kors, J.A. (Jan), Teumer, A. (Alexander), Petersmann, A. (Astrid), Sinner, M.F. (Moritz), Buzkova, P. (Petra), Smith, J.D. (Jonathan), Wagoner, D.R. (David) van, Völker, U. (Uwe), Waldenberger, M. (Melanie), Peters, A. (Annette), Meitinger, T. (Thomas), Limacher, M.C. (Marian C.), Wilhelmsen, K.C., Psaty, B.M. (Bruce M.), Hofman, A. (Albert), Uitterlinden, A.G. (André), Krijthe, B.P. (Bouwe P.), Zhang, Z. (Z.), Schnabel, R.B. (Renate), Kääb, S. (Stefan), Duijn, C.M. (Cornelia) van, Rotter, J.I. (Jerome I.), Sotoodehnia, N. (Nona), Dörr, M. (Marcus), Li, Y. (Yun), Chung, M.K. (Mina), Soliman, E.Z. (Elsayed Z.), Alonso, A. (Alvaro), Whitsel, E.A. (Eric), Stricker, B.H.Ch. (Bruno), Benjamin, E.J. (Emelia J.), Heckbert, S.R. (Susan), and Ellinor, P.T. (Patrick)
Abstract: The P wave on an ECG is a measure of atrial electric function, and its characteristics may serve as predictors for atrial arrhythmias. Increased mean P-wave duration and P-wave terminal force traditionally have been used as markers for left atrial enlargement, and both have been associated with increased risk of atrial fibrillation. Here, we explore the genetic basis of P-wave morphology through meta-analysis of genome-wide association study results for P-wave duration and P-wave terminal force from 12 cohort studies. Methods and Results - We included 44 456 individuals, of which 6778 (16%) were of African ancestry. Genotyping, imputation, and genome-wide association study were performed at each study site. Summary-level results were meta-analyzed centrally using inverse-variance weighting. In meta-analyses of P-wave duration, we identified 6 significant (P<5×10-8) novel loci and replicated a prior association with SCN10A. We identified 3 loci at SCN5A, TBX5, and CAV1/CAV2 that were jointly associated with the PR interval, PR segment, and P-wave duration. We identified 6 novel loci in meta-analysis of P-wave terminal force. Four of the identified genetic loci were significantly associated with gene expression in 329 left atrial samples. Finally, we observed that some of the loci associated with the P wave were linked to overall atrial conduction, whereas others identified distinct phases of atrial conduction. Conclusions - We have identified 6 novel genetic loci associated with P-wave duration and 6 novel loci associated with P-wave terminal force. Future studies of these loci may aid in identifying new targets for drugs that may modify atrial conduction or treat atrial arrhythmias.
Published: 2017
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10. Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis

Author: Hobbs, B.D. (Brian D.), Jong, K. (Kim) de, Lamontagne, M. (Maxime), Bossé, Y. (Yohan), Shrine, N.R.G. (Nick), Artigas, M.S., Wain, L.V. (Louise V), Hall, I.P. (Ian), Jackson, V.E. (Victoria E.), Wyss, A.B. (Annah B.), London, S.J. (Stephanie J), North, K.E. (Kari), Franceschini, N. (Nora), Strachan, D.P. (David), Beaty, T.H. (Terri), Hokanson, J.E. (John E.), Crapo, R.O. (Robert), Castaldi, P.J. (Peter J.), Chase, R.P. (Robert P.), Bartz, T.M. (Traci M.), Heckbert, S.R. (Susan), Psaty, B.M. (Bruce M.), Gharib, S.A. (Sina), Zanen, P. (Pieter), Lammers, J.-W.J. (Jan-Willem), Oudkerk, M. (Matthijs), Groen, H.J.M. (Henk), Locantore, N. (Nicholas), Tal-Singer, R. (Ruth), Rennard, S.I., Vestbo, J. (Jorgen), Timens, W. (Wim), Paré, P.D. (Peter), Latourelle, J.C. (Jeanne), Dupuis, J. (Josée), O'Connor, G.T. (George), Wilk, J.B. (Jemma), Kim, W.J. (Woo Jin), Lee, M.K. (Mi Kyeong), Oh, Y.-M. (Yeon-Mok), Vonk, J.M. (Judith), Koning, H.J. (Harry) de, Leng, S. (Shuguang), Belinsky, S.A. (Steven A.), Tesfaigzi, Y. (Yohannes), Manichaikul, A. (Ani), Wang, X.-Q. (Xin-Qun), Rich, S.S. (Stephen), Barr, R.G. (Graham), Sparrow, D. (David), Litonjua, A.A. (Augusto), Bakke, A.B. (Arnold B.), Gulsvik, A. (Amund), Lahousse, L. (Lies), Brusselle, G.G. (Guy), Stricker, B.H.Ch. (Bruno), Uitterlinden, A.G. (André), Ampleford, E.J. (Elizabeth J.), Bleecker, E.R. (E.), Woodruff, P.G. (Prescott G.), Meyers, D.A. (Deborah A.), Qiao, D. (Dandi), Lomas, D.A. (David A.), Yim, J.-J. (Jae-Joon), Kim, D.K. (Deog Kyeom), Hawrylkiewicz, I. (Iwona), Sliwinski, P. (Pawel), Hardin, M. (Megan), Fingerlin, T.E. (Tasha E.), Schwartz, D.A. (David A.), Postma, D.S. (Dirkje S.), MacNee, W., Tobin, M.D. (Martin), Silverman, E. (Edwin), Boezen, H.M. (Marike), Cho, M.H. (Michael), Hobbs, B.D. (Brian D.), Jong, K. (Kim) de, Lamontagne, M. (Maxime), Bossé, Y. (Yohan), Shrine, N.R.G. (Nick), Artigas, M.S., Wain, L.V. (Louise V), Hall, I.P. (Ian), Jackson, V.E. (Victoria E.), Wyss, A.B. (Annah B.), London, S.J. (Stephanie J), North, K.E. (Kari), Franceschini, N. (Nora), Strachan, D.P. (David), Beaty, T.H. (Terri), Hokanson, J.E. (John E.), Crapo, R.O. (Robert), Castaldi, P.J. (Peter J.), Chase, R.P. (Robert P.), Bartz, T.M. (Traci M.), Heckbert, S.R. (Susan), Psaty, B.M. (Bruce M.), Gharib, S.A. (Sina), Zanen, P. (Pieter), Lammers, J.-W.J. (Jan-Willem), Oudkerk, M. (Matthijs), Groen, H.J.M. (Henk), Locantore, N. (Nicholas), Tal-Singer, R. (Ruth), Rennard, S.I., Vestbo, J. (Jorgen), Timens, W. (Wim), Paré, P.D. (Peter), Latourelle, J.C. (Jeanne), Dupuis, J. (Josée), O'Connor, G.T. (George), Wilk, J.B. (Jemma), Kim, W.J. (Woo Jin), Lee, M.K. (Mi Kyeong), Oh, Y.-M. (Yeon-Mok), Vonk, J.M. (Judith), Koning, H.J. (Harry) de, Leng, S. (Shuguang), Belinsky, S.A. (Steven A.), Tesfaigzi, Y. (Yohannes), Manichaikul, A. (Ani), Wang, X.-Q. (Xin-Qun), Rich, S.S. (Stephen), Barr, R.G. (Graham), Sparrow, D. (David), Litonjua, A.A. (Augusto), Bakke, A.B. (Arnold B.), Gulsvik, A. (Amund), Lahousse, L. (Lies), Brusselle, G.G. (Guy), Stricker, B.H.Ch. (Bruno), Uitterlinden, A.G. (André), Ampleford, E.J. (Elizabeth J.), Bleecker, E.R. (E.), Woodruff, P.G. (Prescott G.), Meyers, D.A. (Deborah A.), Qiao, D. (Dandi), Lomas, D.A. (David A.), Yim, J.-J. (Jae-Joon), Kim, D.K. (Deog Kyeom), Hawrylkiewicz, I. (Iwona), Sliwinski, P. (Pawel), Hardin, M. (Megan), Fingerlin, T.E. (Tasha E.), Schwartz, D.A. (David A.), Postma, D.S. (Dirkje S.), MacNee, W., Tobin, M.D. (Martin), Silverman, E. (Edwin), Boezen, H.M. (Marike), and Cho, M.H. (Michael)
Abstract: Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. We performed a genetic association study in 15,256 cases and 47,936 controls, with replication of select top results (P < 5 × 10-6) in 9,498 cases and 9,748 controls. In the combined meta-analysis, we identified 22 loci associated at genome-wide significance, including 13 new associations with COPD. Nine of these 13 loci have been associated with lung function in general population samples, while 4 (EEFSEC, DSP, MTCL1, and SFTPD) are new. We noted two loci shared with pulmonary fibrosis (FAM13A and DSP) but that had opposite risk alleles for COPD. None of our loci overlapped with genome-wide associations for asthma, although one locus has been implicated in joint susceptibility to asthma and obesity. We also identified genetic correlation between COPD and asthma. Our findings highlight new loci associated with COPD, demonstrate the importance of specific loci associated with lung function to COPD, and identify potential regions of genetic overlap between COPD and other respiratory diseases.
Published: 2017
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11. Discovery of novel heart rate-associated loci using the Exome Chip

Author: Berg, M.E. (Marten) van den, Warren, H. (Helen), Cabrera, C.P. (Claudia P.), Verweij, N. (Niek), Mifsud, B. (Borbala), Haessler, J. (Jeff), Bihlmeyer, N.A. (Nathan A.), Fu, Y.-P. (Yi-Ping), Weiss, S. (Stefan), Lin, H.J. (Henry J.), Grarup, N. (Niels), Li-Gao, R. (Ruifang), Pistis, G. (Giorgio), Shah, N. (Nisha), Brody, J.A. (Jennifer A.), Müller-Nurasyid, M. (Martina), Lin, H. (Honghuang), Mei, H. (Hao), Smith, A.V. (Albert V.), Lyytikäinen, L.-P. (Leo-Pekka), Hall, L.M. (Leanne M.), Setten, J. (Jessica) van, Trompet, S. (Stella), Prins, B.P. (Bram P.), Isaacs, A.J. (Aaron), Radmanesh, F. (Farid), Marten, J. (Jonathan), Entwistle, A. (Aiman), Kors, J.A. (Jan), Silva Aldana, C.T. (Claudia), Alonso, A. (Alvaro), Bis, J.C. (Joshua), Boer, R.A. (Rudolf) de, Haan, H.G. (Hugoline) de, Mutsert, R. (Reneé) de, Dedoussis, G.V. (George), Dominiczak, A. (Anna), Doney, A.S.F. (Alex), Ellinor, P.T. (Patrick), Eppinga, R.N. (Ruben N.), Felix, S.B. (Stephan), Guo, X. (Xiuqing), Hagemeijer, Y. (Yanick), Hansen, T. (T.), Harris, T.B. (Tamara), Heckbert, S.R. (Susan), Huang, P.L. (Paul L.), Hwang, S.-J. (Shih-Jen), Kähönen, M. (Mika), Kanters, J.K., Kolcic, I. (Ivana), Launer, L.J. (Lenore), Li, M. (Man), Yao, J. (Jiefen), Linneberg, A. (Allan), Liu, S. (Simin), MacFarlane, P.W. (Peter), Mangino, M. (Massimo), Morris, A.D. (Andrew D.), Mulas, A. (Antonella), Murray, A.D. (Alison D.), Nelson, C.P. (Christopher P.), Orrù, M. (Marco), Padmanabhan, S. (Sandosh), Peters, A. (Annette), Porteous, D.J. (David J.), Poulter, N.R. (Neil), Psaty, B.M. (Bruce M.), Qi, L. (Lihong), Raitakari, O.T. (Olli T.), Rivadeneira, F. (Fernando), Roselli, C. (Carolina), Rudan, I. (Igor), Sattar, N. (Naveed), Sever, P. (Peter), Sinner, M.F. (Moritz), Soliman, E.Z. (Elsayed), Spector, T.D. (Timothy), Stanton, A. (Alice), Stirrups, K. (Kathy), Taylor, K.D. (Kent), Tobin, M.D. (Martin), Uitterlinden, A.G. (André), Vaartjes, I. (Ilonca), Hoes, A.W. (Arno), van der Meer, P. (Peter), Völker, U. (Uwe), Waldenberger, M. (Melanie), Xie, Z. (Zhijun), Zoledziewska, M. (Magdalena), Tinker, A. (Andrew), Polasek, O. (Ozren), Rosand, J. (Jonathan), Jamshidi, Y. (Yalda), Duijn, C.M. (Cornelia) van, Zeggini, E. (Eleftheria), Jukema, J.W. (Jan Wouter), Asselbergs, F.W. (Folkert), Samani, N.J. (Nilesh), Lehtimäki, T. (Terho), Gudnason, V. (Vilmundur), Wilson, J.F. (James), Lubitz, S.A. (Steven A.), Kääb, S. (Stefan), Sotoodehnia, N. (Nona), Caulfield, M. (Mark), Palmer, C.N.A. (Colin), Sanna, S. (Serena), Mook-Kanamori, D.O. (Dennis), Deloukas, P. (Panos), Pedersen, O. (Oluf), Rotter, J.I. (Jerome I.), Dörr, M. (Marcus), O'Donnell, C.J. (Christopher J.), Hayward, C. (Caroline), Arking, D.E. (Dan), Kooperberg, C. (Charles), van der Harst, P. (Pim), Eijgelsheim, M. (Mark), Stricker, B.H.Ch. (Bruno), Munroe, P. (Patricia), Berg, M.E. (Marten) van den, Warren, H. (Helen), Cabrera, C.P. (Claudia P.), Verweij, N. (Niek), Mifsud, B. (Borbala), Haessler, J. (Jeff), Bihlmeyer, N.A. (Nathan A.), Fu, Y.-P. (Yi-Ping), Weiss, S. (Stefan), Lin, H.J. (Henry J.), Grarup, N. (Niels), Li-Gao, R. (Ruifang), Pistis, G. (Giorgio), Shah, N. (Nisha), Brody, J.A. (Jennifer A.), Müller-Nurasyid, M. (Martina), Lin, H. (Honghuang), Mei, H. (Hao), Smith, A.V. (Albert V.), Lyytikäinen, L.-P. (Leo-Pekka), Hall, L.M. (Leanne M.), Setten, J. (Jessica) van, Trompet, S. (Stella), Prins, B.P. (Bram P.), Isaacs, A.J. (Aaron), Radmanesh, F. (Farid), Marten, J. (Jonathan), Entwistle, A. (Aiman), Kors, J.A. (Jan), Silva Aldana, C.T. (Claudia), Alonso, A. (Alvaro), Bis, J.C. (Joshua), Boer, R.A. (Rudolf) de, Haan, H.G. (Hugoline) de, Mutsert, R. (Reneé) de, Dedoussis, G.V. (George), Dominiczak, A. (Anna), Doney, A.S.F. (Alex), Ellinor, P.T. (Patrick), Eppinga, R.N. (Ruben N.), Felix, S.B. (Stephan), Guo, X. (Xiuqing), Hagemeijer, Y. (Yanick), Hansen, T. (T.), Harris, T.B. (Tamara), Heckbert, S.R. (Susan), Huang, P.L. (Paul L.), Hwang, S.-J. (Shih-Jen), Kähönen, M. (Mika), Kanters, J.K., Kolcic, I. (Ivana), Launer, L.J. (Lenore), Li, M. (Man), Yao, J. (Jiefen), Linneberg, A. (Allan), Liu, S. (Simin), MacFarlane, P.W. (Peter), Mangino, M. (Massimo), Morris, A.D. (Andrew D.), Mulas, A. (Antonella), Murray, A.D. (Alison D.), Nelson, C.P. (Christopher P.), Orrù, M. (Marco), Padmanabhan, S. (Sandosh), Peters, A. (Annette), Porteous, D.J. (David J.), Poulter, N.R. (Neil), Psaty, B.M. (Bruce M.), Qi, L. (Lihong), Raitakari, O.T. (Olli T.), Rivadeneira, F. (Fernando), Roselli, C. (Carolina), Rudan, I. (Igor), Sattar, N. (Naveed), Sever, P. (Peter), Sinner, M.F. (Moritz), Soliman, E.Z. (Elsayed), Spector, T.D. (Timothy), Stanton, A. (Alice), Stirrups, K. (Kathy), Taylor, K.D. (Kent), Tobin, M.D. (Martin), Uitterlinden, A.G. (André), Vaartjes, I. (Ilonca), Hoes, A.W. (Arno), van der Meer, P. (Peter), Völker, U. (Uwe), Waldenberger, M. (Melanie), Xie, Z. (Zhijun), Zoledziewska, M. (Magdalena), Tinker, A. (Andrew), Polasek, O. (Ozren), Rosand, J. (Jonathan), Jamshidi, Y. (Yalda), Duijn, C.M. (Cornelia) van, Zeggini, E. (Eleftheria), Jukema, J.W. (Jan Wouter), Asselbergs, F.W. (Folkert), Samani, N.J. (Nilesh), Lehtimäki, T. (Terho), Gudnason, V. (Vilmundur), Wilson, J.F. (James), Lubitz, S.A. (Steven A.), Kääb, S. (Stefan), Sotoodehnia, N. (Nona), Caulfield, M. (Mark), Palmer, C.N.A. (Colin), Sanna, S. (Serena), Mook-Kanamori, D.O. (Dennis), Deloukas, P. (Panos), Pedersen, O. (Oluf), Rotter, J.I. (Jerome I.), Dörr, M. (Marcus), O'Donnell, C.J. (Christopher J.), Hayward, C. (Caroline), Arking, D.E. (Dan), Kooperberg, C. (Charles), van der Harst, P. (Pim), Eijgelsheim, M. (Mark), Stricker, B.H.Ch. (Bruno), and Munroe, P. (Patricia)
Abstract: Resting heart rate is a heritable trait, and an increase in heart rate is associated with increased mortality risk. Genome-wide association study analyses have found loci associated with resting heart rate, at the time of our study these loci explained 0.9% of the variation. This study aims to discover new genetic loci associated with heart rate from Exome Chip meta-analyses. Heart rate was measured from either elecrtrocardiograms or pulse recordings. We meta-analysed heart rate association results from 104 452 European-ancestry individuals from 30 cohorts, genotyped using the Exome Chip. Twenty-four variants were selected for follow-up in an independent dataset (UK Biobank, N = 134 251). Conditional and gene-based testing was undertaken, and variants were investigated with bioinformatics methods.We discovered five novel heart rate loci, and one new independent low-frequency non-synonymous variant in an established heart rate locus (KIAA1755). Lead variants in four of the novel loci are non-synonymous variants in the genes C10orf71, DALDR3, TESK2 and SEC31B. The variant at SEC31B is significantly associated with SEC31B expression in heart and tibial nerve tissue. Further candidate genes were detected from long-range regulatory chromatin interactions in heart tissue (SCD, SLF2 and MAPK8). We observed significant enrichment in DNase I hypersensitive sites in fetal heart and lung. Moreover, enrichment was seen for the first time in human neuronal progenitor cells (derived from embryonic stem cells) and fetal muscle samples by including our novel variants. Our findings advance the knowledge of the genetic architecture of heart rate, and indicate new candidate genes for follow-up functional studies.
Published: 2017
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12. Cardiac magnetic resonance-measured left atrial volume and function and incident atrial fibrillation

Author: Habibi, M. (Mohammadali), Samiei, S. (Sanaz), Venkatesh, B.A. (Bharath Ambale), Opdahl, A. (Anders), Helle-Valle, T.M. (Thomas M.), Zareian, M. (Mytra), Almeida, A.L.C. (Andre L.C.), Choi, E.-Y. (Eui-Young), Wu, C. (Colin), Alonso, A. (Alvaro), Heckbert, S.R. (Susan), Bluemke, D.A. (David), Lima, J. (Joao), Habibi, M. (Mohammadali), Samiei, S. (Sanaz), Venkatesh, B.A. (Bharath Ambale), Opdahl, A. (Anders), Helle-Valle, T.M. (Thomas M.), Zareian, M. (Mytra), Almeida, A.L.C. (Andre L.C.), Choi, E.-Y. (Eui-Young), Wu, C. (Colin), Alonso, A. (Alvaro), Heckbert, S.R. (Susan), Bluemke, D.A. (David), and Lima, J. (Joao)
Abstract: Background - Early detection of structural changes in left atrium (LA) before atrial fibrillation (AF) development could be helpful in identification of those at higher risk for AF. Using cardiac magnetic resonance imaging, we examined the association of LA volume and function, and incident AF in a multiethnic population free of clinical cardiovascular diseases. Methods and Results - In a case-cohort study embedded in MESA (Multi-Ethnic Study of Atherosclerosis), baseline LA size and function assessed by cardiac magnetic resonance feature-tracking were compared between 197 participants with incident AF and 322 participants randomly selected from the whole MESA cohort. Participants were followed up for 8 years. Incident AF cases had a larger LA volume and decreased passive, active, and total LA emptying fractions and peak global LA longitudinal strain (peak LA strain) at baseline. In multivariable analysis, elevated LA maximum volume index (hazard ratio, 1.38 per SD; 95% confidence interval, 1.01-1.89) and decreased peak LA strain (hazard ratio, 0.68 per SD; 95% confidence interval, 0.48-0.96), and passive and total LA emptying fractions (hazard ratio for passive LA emptying fractions, 0.55 per SD; 95% confidence interval, 0.40-0.75 and hazard ratio for active LA emptying fractions, 0.70 per SD; 95% confidence interval, 0.52-0.95), but not active LA emptying fraction, were associated with incident AF. Conclusions - Elevated LA volumes and decreased passive and total LA emptying fractions were independently associated with incident AF in an asymptomatic multiethnic population. Including LA functional variables along with other risk factors of AF may help to better risk stratify individuals at risk of AF development.
Published: 2016
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13. Gene-gene Interaction Analyses for Atrial Fibrillation

Author: Lin, H. (Honghuang), Mueller-Nurasyid, M., Smith, A.V. (Albert Vernon), Arking, D.E. (Dan), Barnard, J. (John), Bartz, T.M. (Traci M.), Lunetta, K.L. (Kathryn), Lohman, K. (Kurt), Kleber, M.E. (Marcus), Lubitz, S.A. (Steven), Geelhoed, B. (Bastiaan), Trompet, S. (Stella), Niemeijer, M.N. (Maartje), Kacprowski, T. (Tim), Chasman, D.I. (Daniel), Klarin, D. (Derek), Sinner, M.F. (Moritz), Waldenberger, M. (Melanie), Meitinger, T. (Thomas), Harris, T.B. (Tamara), Launer, L.J. (Lenore), Soliman, E.Z. (Elsayed Z.), Chen, L. (Lin), Smith, J.D. (Jonathan), Wagoner, D.R. (David) van, Rotter, J.I. (Jerome I.), Psaty, B.M. (Bruce), Xie, Z. (Zhijun), Hendricks, A.E. (Audrey E.), Ding, J. (Jingzhong), Delgado, G.E. (Graciela E.), Verweij, N. (Niek), Harst, P. (Pim) van der, MacFarlane, P.W. (Peter), Ford, I. (Ian), Hofman, A. (Albert), Uitterlinden, A.G. (André), Heeringa, J. (Jan), Franco, O.H. (Oscar), Kors, J.A. (Jan), Weiss, S. (Stefan), Völzke, H. (Henry), Rose, L.M. (Lynda), Natarajan, P. (Pradeep), Kathiresan, S. (Sekar), Kääb, S. (Stefan), Gudnason, V. (Vilmundur), Alonso, A. (Alvaro), Chung, M.K. (Mina), Heckbert, S.R. (Susan), Benjamin, E.J. (Emelia), Liu, Y. (YongMei), März, W. (Winfried), Rienstra, S.A., Jukema, J.W. (Jan Wouter), Stricker, B.H.Ch. (Bruno), Dörr, M. (Marcus), Albert, C.M. (Christine), Ellinor, P.T. (Patrick), Lin, H. (Honghuang), Mueller-Nurasyid, M., Smith, A.V. (Albert Vernon), Arking, D.E. (Dan), Barnard, J. (John), Bartz, T.M. (Traci M.), Lunetta, K.L. (Kathryn), Lohman, K. (Kurt), Kleber, M.E. (Marcus), Lubitz, S.A. (Steven), Geelhoed, B. (Bastiaan), Trompet, S. (Stella), Niemeijer, M.N. (Maartje), Kacprowski, T. (Tim), Chasman, D.I. (Daniel), Klarin, D. (Derek), Sinner, M.F. (Moritz), Waldenberger, M. (Melanie), Meitinger, T. (Thomas), Harris, T.B. (Tamara), Launer, L.J. (Lenore), Soliman, E.Z. (Elsayed Z.), Chen, L. (Lin), Smith, J.D. (Jonathan), Wagoner, D.R. (David) van, Rotter, J.I. (Jerome I.), Psaty, B.M. (Bruce), Xie, Z. (Zhijun), Hendricks, A.E. (Audrey E.), Ding, J. (Jingzhong), Delgado, G.E. (Graciela E.), Verweij, N. (Niek), Harst, P. (Pim) van der, MacFarlane, P.W. (Peter), Ford, I. (Ian), Hofman, A. (Albert), Uitterlinden, A.G. (André), Heeringa, J. (Jan), Franco, O.H. (Oscar), Kors, J.A. (Jan), Weiss, S. (Stefan), Völzke, H. (Henry), Rose, L.M. (Lynda), Natarajan, P. (Pradeep), Kathiresan, S. (Sekar), Kääb, S. (Stefan), Gudnason, V. (Vilmundur), Alonso, A. (Alvaro), Chung, M.K. (Mina), Heckbert, S.R. (Susan), Benjamin, E.J. (Emelia), Liu, Y. (YongMei), März, W. (Winfried), Rienstra, S.A., Jukema, J.W. (Jan Wouter), Stricker, B.H.Ch. (Bruno), Dörr, M. (Marcus), Albert, C.M. (Christine), and Ellinor, P.T. (Patrick)
Abstract: Atrial fibrillation (AF) is a heritable disease that affects more than thirty million individuals worldwide. Extensive efforts have been devoted to the study of genetic determinants of AF. The objective of our study is to examine the effect of gene-gene interaction on AF susceptibility. We performed a large-scale association analysis of gene-gene interactions with AF in 8,173 AF cases, and 65,237 AF-free referents collected from 15 studies for discovery. We examined putative interactions between genome-wide SNPs and 17 known AF-related SNPs. The top interactions were then tested for association in an
Published: 2016
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14. Association of Forced Vital Capacity with the Developmental Gene NCOR2

Author: Minelli, C. (Cosetta), Dean, C.H. (Charlotte H.), Hind, M. (Matthew), Alves, A.C. (Alexessander Couto), Amaral, A.F.S. (André), Siroux, V. (V.), Huikari, V. (Ville), Artigas, M.S., Evans, D.M. (David M.), Loth, D.W. (Daan), Bossé, Y. (Yohan), Postma, D.S. (Dirkje), Sin, D.D., Thompson, J.R. (John), Demenais, F. (Florence), Henderson, J. (John), Bouzigon, E. (Emmanuelle), Jarvis, D.L. (Deborah), Jarvelin, M.-R. (Marjo-Riitta), Burney, P.G., Gharib, S.A. (Sina), Wain, L.V. (Louise), Franceschini, N. (Nora), Koch, B. (Beate), Pottinger, T.D. (Tess), Smith, A.V. (Albert), Duan, Q. (Qing), Oldmeadow, C. (Christopher), Lee, M.K. (Mi Kyeong), Strachan, D.P. (David P.), James, A.L. (Alan L.), Huffman, J.E. (Jennifer), Vitart, V. (Veronique), Ramasamy, A. (Adaikalavan), Wareham, N.J. (Nicholas J.), Kaprio, J. (Jaakko), Wang, X.-Q. (Xin-Qun), Trochet, H. (Holly), Kähönen, M. (Mika), Flexeder, C. (Claudia), Albrecht, E. (Eva), Lopez, L.M. (Lorna M.), Jong, K. (Kim) de, Thyagarajan, B. (Bharat), Enroth, S. (Stefan), Omenaas, E. (Ernst), Joshi, P.K. (Peter), Fall, M. (Magnus), Viñuela, A. (Ana), Launer, L.J. (Lenore), Loehr, L.R. (Laura), Fornage, M. (Myriam), Li, G. (Guo), Wilk, J.B. (Jemma), Tang, W. (Wenbo), Manichaikul, A. (Ani), Lahousse, L. (Lies), Harris, T.B. (Tamara), North, K.E. (Kari E.), Rudnicka, A.R. (Alicja), Hui, J. (Jennie), Gu, X. (Xiangjun), Lumley, T. (Thomas), Wright, A.F. (Alan F.), Hastie, N. (Nick), Campbell, S. (Susan), Kumar, R. (Rajesh), Pin, I. (Isabelle), Scott, R.A. (Robert), Pietilainen, K.H. (Kirsi Hannele), Surakka, I. (Ida), Liu, Y. (YongMei), Holliday, E.G. (Elizabeth), Schulz, H. (Holger), Heinrich, J. (Joachim), Davies, G. (Gail), MVonk, J. (Judith), Wojczynski, M.K. (Mary ), Pouta, A. (Anneli), Johansson, A. (Åsa), Wild, S. (Sarah), Ingelsson, E. (Erik), Rivadeneira Ramirez, F. (Fernando), Völzke, H. (Henry), Hysi, P.G. (Pirro), Eiriksdottir, G. (Gudny), Morrison, A.C. (Alanna), Rotter, J.I. (Jerome I.), Gao, W. (Wei), White, W.B. (Wendy), Rich, S.S. (Stephen S.), Hofman, A. (Albert), Aspelund, T. (Thor), Couper, D.J. (David), Smith, L.J. (Lewis J.), Psaty, B.M. (Bruce), Lohman, K. (Kurt), Burchard, E.G. (Esteban), Uitterlinden, A.G. (André), Garcia, M. (Melissa), Joubert, B.R. (Bonnie), McArdle, W.L. (Wendy), Musk, A.B. (A Bill), Hansel, C.R.W. (Christian), Heckbert, S.R. (Susan), Zgaga, L. (Lina), Meurs, J.B.J. (Joyce) van, Navarro, P. (Pau), Rudan, I. (Igor), Oh, Y.-M. (Yeon-Mok), Redline, S. (Susan), Jarvis, D.L. (Deborah L.), Zhao, J.H. (Jing Hua), Rantanen, T. (Taina), Connor, G.T. (George) O', Ripatti, S. (Samuli), Scott, R.J. (Rodney), Karrasch, S. (Stefan), Grallert, H. (Harald), Gaddis, N.C. (Nathan C.), MStarr, J. (John), Wijmenga, C. (Cisca), Minster, R.L. (Ryan), Lederer, C.W. (Carsten), Pekkanen, J. (Juha), Gyllensten, U. (Ulf), Campbell, H. (Harry), Morris, A.P. (Andrew), Gläser, S. (Sven), Hammond, C.J. (Christopher J.), MBurkart, K. (Kristin), Beilby, J. (John), Kritchevsky, S.B. (Stephen B.), Gudnason, V. (Vilmundur), Hancock, D.B. (Dana), Williams, O. (O'Dale), Polasek, O. (Ozren), Zemunik, T. (Tatijana), Kolcic, I. (Ivana), Petrini, M.F. (Marcy), Wjst, M. (Matthias), Kim, W.J. (Woo Jin), Porteous, D.J. (David J.), Scotland, G. (Generation), Smith, B.H. (Blair), Viljanen, A. (Anne), Heliovaara, M. (Markku), Attia, J. (John), Sayers, I. (Ian), Hampel, R. (Regina), Gieger, C. (Christian), Deary, I.J. (Ian), Boezen, H.M. (Marike), Newman, A.B. (Anne B.), Wilson, J.F. (James F), Lind, L. (Lars), Stricker, B.H.Ch. (Bruno), Teumer, A. (Alexander), Spector, T.D. (Timothy), Melén, E. (Erik), Peters, M.J. (Marjolein), Lange, L.A. (Leslie), Barr, R.G. (Graham), Bracke, K.R. (Ken), MVerhamme, F. (Fien), Sung, J. (Joohon), Hiemstra, P.S. (Pieter), Cassano, P.A. (Patricia), Sood, A. (Akshay), Hayward, C. (Caroline), Dupuis, J. (Josée), Hall, I.P. (Ian), Brusselle, G.G. (Guy), Tobin, M.D. (Martin), London, S.J. (Stephanie J), Minelli, C. (Cosetta), Dean, C.H. (Charlotte H.), Hind, M. (Matthew), Alves, A.C. (Alexessander Couto), Amaral, A.F.S. (André), Siroux, V. (V.), Huikari, V. (Ville), Artigas, M.S., Evans, D.M. (David M.), Loth, D.W. (Daan), Bossé, Y. (Yohan), Postma, D.S. (Dirkje), Sin, D.D., Thompson, J.R. (John), Demenais, F. (Florence), Henderson, J. (John), Bouzigon, E. (Emmanuelle), Jarvis, D.L. (Deborah), Jarvelin, M.-R. (Marjo-Riitta), Burney, P.G., Gharib, S.A. (Sina), Wain, L.V. (Louise), Franceschini, N. (Nora), Koch, B. (Beate), Pottinger, T.D. (Tess), Smith, A.V. (Albert), Duan, Q. (Qing), Oldmeadow, C. (Christopher), Lee, M.K. (Mi Kyeong), Strachan, D.P. (David P.), James, A.L. (Alan L.), Huffman, J.E. (Jennifer), Vitart, V. (Veronique), Ramasamy, A. (Adaikalavan), Wareham, N.J. (Nicholas J.), Kaprio, J. (Jaakko), Wang, X.-Q. (Xin-Qun), Trochet, H. (Holly), Kähönen, M. (Mika), Flexeder, C. (Claudia), Albrecht, E. (Eva), Lopez, L.M. (Lorna M.), Jong, K. (Kim) de, Thyagarajan, B. (Bharat), Enroth, S. (Stefan), Omenaas, E. (Ernst), Joshi, P.K. (Peter), Fall, M. (Magnus), Viñuela, A. (Ana), Launer, L.J. (Lenore), Loehr, L.R. (Laura), Fornage, M. (Myriam), Li, G. (Guo), Wilk, J.B. (Jemma), Tang, W. (Wenbo), Manichaikul, A. (Ani), Lahousse, L. (Lies), Harris, T.B. (Tamara), North, K.E. (Kari E.), Rudnicka, A.R. (Alicja), Hui, J. (Jennie), Gu, X. (Xiangjun), Lumley, T. (Thomas), Wright, A.F. (Alan F.), Hastie, N. (Nick), Campbell, S. (Susan), Kumar, R. (Rajesh), Pin, I. (Isabelle), Scott, R.A. (Robert), Pietilainen, K.H. (Kirsi Hannele), Surakka, I. (Ida), Liu, Y. (YongMei), Holliday, E.G. (Elizabeth), Schulz, H. (Holger), Heinrich, J. (Joachim), Davies, G. (Gail), MVonk, J. (Judith), Wojczynski, M.K. (Mary ), Pouta, A. (Anneli), Johansson, A. (Åsa), Wild, S. (Sarah), Ingelsson, E. (Erik), Rivadeneira Ramirez, F. (Fernando), Völzke, H. (Henry), Hysi, P.G. (Pirro), Eiriksdottir, G. (Gudny), Morrison, A.C. (Alanna), Rotter, J.I. (Jerome I.), Gao, W. (Wei), White, W.B. (Wendy), Rich, S.S. (Stephen S.), Hofman, A. (Albert), Aspelund, T. (Thor), Couper, D.J. (David), Smith, L.J. (Lewis J.), Psaty, B.M. (Bruce), Lohman, K. (Kurt), Burchard, E.G. (Esteban), Uitterlinden, A.G. (André), Garcia, M. (Melissa), Joubert, B.R. (Bonnie), McArdle, W.L. (Wendy), Musk, A.B. (A Bill), Hansel, C.R.W. (Christian), Heckbert, S.R. (Susan), Zgaga, L. (Lina), Meurs, J.B.J. (Joyce) van, Navarro, P. (Pau), Rudan, I. (Igor), Oh, Y.-M. (Yeon-Mok), Redline, S. (Susan), Jarvis, D.L. (Deborah L.), Zhao, J.H. (Jing Hua), Rantanen, T. (Taina), Connor, G.T. (George) O', Ripatti, S. (Samuli), Scott, R.J. (Rodney), Karrasch, S. (Stefan), Grallert, H. (Harald), Gaddis, N.C. (Nathan C.), MStarr, J. (John), Wijmenga, C. (Cisca), Minster, R.L. (Ryan), Lederer, C.W. (Carsten), Pekkanen, J. (Juha), Gyllensten, U. (Ulf), Campbell, H. (Harry), Morris, A.P. (Andrew), Gläser, S. (Sven), Hammond, C.J. (Christopher J.), MBurkart, K. (Kristin), Beilby, J. (John), Kritchevsky, S.B. (Stephen B.), Gudnason, V. (Vilmundur), Hancock, D.B. (Dana), Williams, O. (O'Dale), Polasek, O. (Ozren), Zemunik, T. (Tatijana), Kolcic, I. (Ivana), Petrini, M.F. (Marcy), Wjst, M. (Matthias), Kim, W.J. (Woo Jin), Porteous, D.J. (David J.), Scotland, G. (Generation), Smith, B.H. (Blair), Viljanen, A. (Anne), Heliovaara, M. (Markku), Attia, J. (John), Sayers, I. (Ian), Hampel, R. (Regina), Gieger, C. (Christian), Deary, I.J. (Ian), Boezen, H.M. (Marike), Newman, A.B. (Anne B.), Wilson, J.F. (James F), Lind, L. (Lars), Stricker, B.H.Ch. (Bruno), Teumer, A. (Alexander), Spector, T.D. (Timothy), Melén, E. (Erik), Peters, M.J. (Marjolein), Lange, L.A. (Leslie), Barr, R.G. (Graham), Bracke, K.R. (Ken), MVerhamme, F. (Fien), Sung, J. (Joohon), Hiemstra, P.S. (Pieter), Cassano, P.A. (Patricia), Sood, A. (Akshay), Hayward, C. (Caroline), Dupuis, J. (Josée), Hall, I.P. (Ian), Brusselle, G.G. (Guy), Tobin, M.D. (Martin), and London, S.J. (Stephanie J)
Abstract: Background Forced Vital Capacity (FVC) is an important predictor of all-cause mortality in the absence of chronic respiratory conditions. Epidemiological evidence highlights the role of early life factors on adult FVC, pointing to environmental exposures and genes affecting lung development as risk factors for low FVC later in life. Although highly heritable, a small number of genes have been found associated with FVC, and we aimed at identifying further genetic variants by focusing on lung development genes. Methods Per-allele effects of 24,728 SNPs in 403 genes involved in lung development were tested in 7,749 adults from three studies (NFBC1966, ECRHS, EGEA). The most significant SNP for the top 25 genes was followed-up in 46,103 adults (CHARGE and SpiroMeta consortia) and 5,062 chil
Published: 2016
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15. Genome-Wide Association Study for Incident Myocardial Infarction and Coronary Heart Disease in Prospective Cohort Studies: The CHARGE Consortium

Author: Dehghan, A. (Abbas), Bis, J.C. (Joshua), White, C.C. (Charles), Smith, A.V. (Albert V.), Morrison, A.C. (Alanna), Cupples, L.A. (Adrienne), Trompet, S. (Stella), Chasman, D.I. (Daniel I.), Lumley, T. (Thomas), Völker, U. (Uwe), Buckley, B.M. (Brendan M.), Ding, J. (Jingzhong), Jensen, M.K. (Majken K.), Folsom, A.R. (Aaron R.), Kritchevsky, S.B. (Stephen), Girman, C.J. (Cynthia J.), Ford, I., Dörr, M. (Marcus), Salomaa, V. (Veikko), Uitterlinden, A.G. (André), Eiriksdottir, G. (Gudny), Vasan, R.S. (Ramachandran S.), Franceschini, N. (Nora), Carty, C. (Cara), Virtamo, J. (Jarmo), Demissie, S. (Serkalem), Amouyel, P. (Philippe), Arveiler, D. (Dominique), Heckbert, S.R. (Susan), Ferrieres, J. (Jean), Ducimetiere, P. (P.), Smith, N.L. (Nicholas), Wang, Y.A. (Ying), Siscovick, D.S. (David), Rice, K.M. (Kenneth), Wiklund, P.-G. (Per-Gunnar), Taylor, K.D. (Kent), Evans, A. (Alun), Kee, F. (Frank), Rotter, J.I. (Jerome I.), Karvanen, J. (Juha), Kuulasmaa, K. (Kari), Heiss, G. (Gerardo), Kraft, P. (Peter), Launer, L.J. (Lenore), Hofman, A. (Albert), Markus, M.R.P. (Marcello R.P.), Rose, L.M. (Lynda), Silander, K. (Kaisa), Wagner, P.J. (Peter), Benjamin, E.J. (Emelia), Lohman, K. (Kurt), Stott, D.J. (David. J.), Rivadeneira Ramirez, F. (Fernando), Harris, T.B. (Tamara), Levy, D. (Daniel), Liu, Y. (YongMei), Rimm, E.B. (Eric B.), Jukema, J.W. (Jan Wouter), Volzke, H. (Henry), Ridker, P.M. (Paul M.), Blankenberg, S. (Stefan), Franco, O.H. (Oscar), Gudnason, V. (Vilmundur), Psaty, B.M. (Bruce), Boerwinkle, E.A. (Eric), O'Donnell, C.J. (Christopher J.), Dehghan, A. (Abbas), Bis, J.C. (Joshua), White, C.C. (Charles), Smith, A.V. (Albert V.), Morrison, A.C. (Alanna), Cupples, L.A. (Adrienne), Trompet, S. (Stella), Chasman, D.I. (Daniel I.), Lumley, T. (Thomas), Völker, U. (Uwe), Buckley, B.M. (Brendan M.), Ding, J. (Jingzhong), Jensen, M.K. (Majken K.), Folsom, A.R. (Aaron R.), Kritchevsky, S.B. (Stephen), Girman, C.J. (Cynthia J.), Ford, I., Dörr, M. (Marcus), Salomaa, V. (Veikko), Uitterlinden, A.G. (André), Eiriksdottir, G. (Gudny), Vasan, R.S. (Ramachandran S.), Franceschini, N. (Nora), Carty, C. (Cara), Virtamo, J. (Jarmo), Demissie, S. (Serkalem), Amouyel, P. (Philippe), Arveiler, D. (Dominique), Heckbert, S.R. (Susan), Ferrieres, J. (Jean), Ducimetiere, P. (P.), Smith, N.L. (Nicholas), Wang, Y.A. (Ying), Siscovick, D.S. (David), Rice, K.M. (Kenneth), Wiklund, P.-G. (Per-Gunnar), Taylor, K.D. (Kent), Evans, A. (Alun), Kee, F. (Frank), Rotter, J.I. (Jerome I.), Karvanen, J. (Juha), Kuulasmaa, K. (Kari), Heiss, G. (Gerardo), Kraft, P. (Peter), Launer, L.J. (Lenore), Hofman, A. (Albert), Markus, M.R.P. (Marcello R.P.), Rose, L.M. (Lynda), Silander, K. (Kaisa), Wagner, P.J. (Peter), Benjamin, E.J. (Emelia), Lohman, K. (Kurt), Stott, D.J. (David. J.), Rivadeneira Ramirez, F. (Fernando), Harris, T.B. (Tamara), Levy, D. (Daniel), Liu, Y. (YongMei), Rimm, E.B. (Eric B.), Jukema, J.W. (Jan Wouter), Volzke, H. (Henry), Ridker, P.M. (Paul M.), Blankenberg, S. (Stefan), Franco, O.H. (Oscar), Gudnason, V. (Vilmundur), Psaty, B.M. (Bruce), Boerwinkle, E.A. (Eric), and O'Donnell, C.J. (Christopher J.)
Abstract: Background Data are limited on genome-wide association studies (GWAS) for incident coronary heart disease (CHD). Moreover, it is not known whether genetic variants identified to date also associate with risk of CHD in a prospective setting. Methods We performed a two-stageGWAS analysis of incident myocardial infarction (MI) and CHD in a total of 64,297 individuals (including 3898MI cases, 5465 CHD cases). SNPs that passed an arbitrary threshold of 5×10-6 in Stage I were taken to Stage II for further discovery. Furthermore, in an analysis of prognosis, we studied whether known SNPs from former GWAS were associated with totalmortality in individuals who experienced MI during follow-up. Results In Stage I 15 loci passed the threshold of 5×10-6; 8 loci for MI and 8 loci for CHD, for which one locus overlapped and none were reported in previous GWAS meta-analyses. We took 60 SNPs representing these 15 loci to Stage II of discovery. Four SNPs near QKI showed nominally significant association with MI (p-value<8.8×10-3) and three exceeded the genome-wide significance threshold when Stage I and Stage II results were combined (top SNP rs6941513: p = 6.2×10-9). Despite excellent power, the 9p21 locus SNP (rs1333049) was only modestly associated with MI (HR = 1.09, p-value = 0.02) and marginally with CHD (HR = 1.06, p-value = 0.08). Among an inception cohort of those who experienced MI during follow-up, the risk allele of rs1333049 was associated with a decreased risk of subsequent mortality (HR = 0.90, p-value = 3.2×10-3). Conclusions QKI represents a novel locus that may serve as a predictor of incident CHD in prospective studies. The association of the 9p21 locus both with increased risk of first myocardial infarction and longer survival after MI highlights the importance of study design in investigating genetic determinants of complex disorders.
Published: 2016
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16. Drug-gene interactions of antihypertensive medications and risk of incident cardiovascular disease: A pharmacogenomics study from the CHARGE consortium

Author: Bis, J.C. (Joshua), Sitlani, C.M. (Colleen), Irvin, R. (Ryan), Avery, C.L., Smith, A.V. (Davey), Sun, F. (Fangui), Evans, D.S. (Daniel), Musani, S. (Solomon), Li, X. (Xiaohui), Trompet, S. (Stella), Krijthe, B.P. (Bouwe), Harris, T.B. (Tamara), Quibrera, P.M. (P. Miguel), Brody, J.A. (Jennifer A.), Demissie, S. (Serkalem), Davis, B.R. (Barry), Wiggins, K.L. (Kerri), Tranah, G.J. (Gregory), Lange, L.A. (Leslie), Sotoodehnia, N. (Nona), Stott, D.J. (David. J.), Franco, O.H. (Oscar), Launer, L.J. (Lenore), Stürmer, T., Taylor, K.D. (Kent), Cupples, L.A. (Adrienne), Eckfeldt, J.H. (John), Smith, N.L. (Nicholas), Liu, Y. (YongMei), Wilson, J.G. (James), Heckbert, S.R. (Susan), Buckley, B.M. (Brendan M.), Ikram, M.A. (Arfan), Boerwinkle, E.A. (Eric), Chen, Y.-D.I. (Yii-Der Ida), De Craen, A.J.M. (Anton J. M.), Uitterlinden, A.G. (André), Rotter, J.I. (Jerome I.), Ford, I., Hofman, A. (Albert), Sattar, N. (Naveed), Slagboom, P.E. (Eline), Westendorp, R.G.J. (Rudi), Gudnason, V. (Vilmundur), Vasan, R.S. (Ramachandran S.), Lumley, T. (Thomas), Cummings, S.R. (Steven R.), Taylor, H.A. (Herman), Post, W. (Wendy), Jukema, J.W. (Jan Wouter), Stricker, B.H.Ch. (Bruno), Whitsel, E.A. (Eric), Psaty, B.M. (Bruce), Arnett, D.K. (Donna), Bis, J.C. (Joshua), Sitlani, C.M. (Colleen), Irvin, R. (Ryan), Avery, C.L., Smith, A.V. (Davey), Sun, F. (Fangui), Evans, D.S. (Daniel), Musani, S. (Solomon), Li, X. (Xiaohui), Trompet, S. (Stella), Krijthe, B.P. (Bouwe), Harris, T.B. (Tamara), Quibrera, P.M. (P. Miguel), Brody, J.A. (Jennifer A.), Demissie, S. (Serkalem), Davis, B.R. (Barry), Wiggins, K.L. (Kerri), Tranah, G.J. (Gregory), Lange, L.A. (Leslie), Sotoodehnia, N. (Nona), Stott, D.J. (David. J.), Franco, O.H. (Oscar), Launer, L.J. (Lenore), Stürmer, T., Taylor, K.D. (Kent), Cupples, L.A. (Adrienne), Eckfeldt, J.H. (John), Smith, N.L. (Nicholas), Liu, Y. (YongMei), Wilson, J.G. (James), Heckbert, S.R. (Susan), Buckley, B.M. (Brendan M.), Ikram, M.A. (Arfan), Boerwinkle, E.A. (Eric), Chen, Y.-D.I. (Yii-Der Ida), De Craen, A.J.M. (Anton J. M.), Uitterlinden, A.G. (André), Rotter, J.I. (Jerome I.), Ford, I., Hofman, A. (Albert), Sattar, N. (Naveed), Slagboom, P.E. (Eline), Westendorp, R.G.J. (Rudi), Gudnason, V. (Vilmundur), Vasan, R.S. (Ramachandran S.), Lumley, T. (Thomas), Cummings, S.R. (Steven R.), Taylor, H.A. (Herman), Post, W. (Wendy), Jukema, J.W. (Jan Wouter), Stricker, B.H.Ch. (Bruno), Whitsel, E.A. (Eric), Psaty, B.M. (Bruce), and Arnett, D.K. (Donna)
Abstract: Background Hypertension is a major risk factor for a spectrum of cardiovascular diseases (CVD), including myocardial infarction, sudden death, and stroke. In the US, over 65 million people have high blood pressure and a large proportion of these individuals are prescribed antihypertensive medications. Although large long-term clinical trials conducted in the last several decades have identified a number of effective antihypertensive treatments that reduce the risk of future clinical complications, responses to therapy and protection from cardiovascular events vary among individuals. Methods Using a genome-wide association study among 21,267 participants with pharmaceutically treated hypertension, we explored the hypothesis that genetic variants might influence or modify the effectiveness of common antihypertensive therapies on the risk ofmajor cardiovascular outcomes. The classes of drug treatments included angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers, and diuretics. In the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, each study performed array-based genome-wide genotyping, imputed to HapMap Phase II reference panels, and used additive genetic models in proportional hazards or logistic regressionmodels to evaluate drug-gene interactions for each of four therapeutic drug classes. We used meta-analysis to combine study-specific interaction estimates for approximately 2 million single nucleotide polymorphisms (SNPs) in a discovery analysis among 15,375 European Ancestry participants (3,527 CVD cases) with targeted follow-up in a case-only study of 1,751 European Ancestry GenHAT participants as well as among 4,141 African-Americans (1,267 CVD cases). Results Although drug-SNP interactions were biologically plausible, exposures and outcomes were well measured, and power was sufficient to detect modest interactions, we did not identify any statistically significant interactions from t
Published: 2015
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17. Genome-wide association analysis identifies six new loci associated with forced vital capacity

Author: Loth, D.W. (Daan), Artigas, M.S., Gharib, S.A. (Sina), Wain, L.V. (Louise), Franceschini, N. (Nora), Koch, B. (Beate), Pottinger, T.D. (Tess), Smith, A.V. (Davey), Duan, Q. (Qing), Oldmeadow, C. (Christopher), Lee, M.K. (Mi Kyeong), Strachan, D.P. (David), James, A.L. (Alan), Huffman, J.E. (Jennifer), Vitart, V. (Veronique), Ramasamy, A. (Adaikalavan), Wareham, N.J. (Nick), Kaprio, J. (Jaakko), Wang, X.-Q. (Xin-Qun), Trochet, H. (Holly), Kähönen, M. (Mika), Flexeder, C. (Claudia), Albrecht, E. (Eva), Lopez, L.M. (Lorna), Thyagarajan, B. (Bharat), Alves, A.C. (Alexessander Couto), Enroth, S. (Stefan), Omenaas, E. (Ernst), Joshi, P.K. (Peter), Fall, M. (Magnus), Viñuela, A. (Ana), Launer, L.J. (Lenore), Loehr, L.R. (Laura), Fornage, M. (Myriam), Li, G. (Guo), Wilk, J.B. (Jemma), Tang, W. (Wenbo), Manichaikul, A. (Ani), Lahousse, L. (Lies), Harris, T.B. (Tamara), North, K.E. (Kari), Rudnicka, A.R. (Alicja), Hui, J. (Jennie), Gu, X. (Xiangjun), Lumley, T. (Thomas), Wright, A.F. (Alan), Hastie, N. (Nick), Campbell, S. (Susan), Kumar, R. (Rajesh), Pin, I. (Isabelle), Scott, R.A. (Robert), Pietilainen, K.H. (Kirsi Hannele), Surakka, I. (Ida), Liu, Y. (YongMei), Holliday, E.G. (Elizabeth), Schulz, H. (Holger), Heinrich, J. (Joachim), Davies, G. (Gail), Vonk, J.M. (Judith), Wojczynski, M.K. (Mary ), Pouta, A. (Anneli), Johansson, A. (Åsa), Wild, S.H. (Sarah), Ingelsson, E. (Erik), Rivadeneira Ramirez, F. (Fernando), Völzke, H. (Henry), Hysi, P.G. (Pirro), Eiriksdottir, G. (Gudny), Morrison, A.C. (Alanna), Rotter, J.I. (Jerome), Gao, W. (Wei), Postma, D.S. (Dirkje), White, W.B. (Wendy), Rich, S.S. (Stephen), Hofman, A. (Albert), Aspelund, T. (Thor), Couper, D. (David), Smith, L.J. (Lewis), Psaty, B.M. (Bruce), Lohman, K. (Kurt), Burchard, E.G. (Esteban), Uitterlinden, A.G. (André), Garcia, M. (Melissa), Joubert, B.R. (Bonnie), McArdle, W.L. (Wendy), Musk, A.W. (Arthur), Hansel, C.R.W. (Christian), Heckbert, S.R. (Susan), Zgaga, L. (Lina), Meurs, J.B.J. (Joyce) van, Navarro, P. (Pau), Rudan, I. (Igor), Oh, Y.-M. (Yeon-Mok), Redline, S. (Susan), Jarvis, D.L. (Deborah), Zhao, J.H. (Jing Hua), Rantanen, T. (Taina), O'Connor, G.T. (George), Ripatti, S. (Samuli), Scott, R.J. (Rodney), Karrasch, S. (Stefan), Grallert, H. (Harald), Gaddis, N.C. (Nathan), Starr, J.M. (John), Wijmenga, C. (Cisca), Minster, R.L. (Ryan), Lederer, C.W. (Carsten), Pekkanen, J. (Juha), Gyllensten, U. (Ulf), Campbell, H. (Harry), Morris, A.P. (Andrew), Gläser, S. (Sven), Hammond, C.J. (Christopher), Burkart, K.M. (Kristin), Beilby, J.P. (John), Kritchevsky, S.B. (Stephen), Gudnason, V. (Vilmundur), Hancock, D.B. (Dana), Williams, O.D. (Dale), Polasek, O. (Ozren), Zemunik, T. (Tatijana), Kolcic, I. (Ivana), Petrini, M.F. (Marcy), Jong, K.T. (Kim) de, Wjst, M. (Matthias), Kim, W.H. (Woo), Porteous, D.J. (David J.), Scotland, G. (Generation), Smith, B.H. (Blair), Viljanen, A. (Anne), Heliovaara, M. (Markku), Attia, J. (John), Sayers, I. (Ian), Hampel, R. (Regina), Gieger, C. (Christian), Deary, I.J. (Ian), Boezen, H.M. (Marike), Newman, A.B. (Anne), Jarvelin, M.-R. (Marjo-Riitta), Wilson, J.F. (James), Lind, L. (Lars), Stricker, B.H.Ch. (Bruno), Teumer, A. (Alexander), Spector, T.D. (Timothy), Melén, E. (Erik), Peters, M.J. (Marjolein), Lange, L.A. (Leslie), Barr, R.G. (Graham), Bracke, K.R. (Ken), Verhamme, F.M. (Fien), Sung, J. (Joohon), Hiemstra, P.S. (Pieter), Cassano, P.A. (Patricia), Sood, A. (Akshay), Hayward, C. (Caroline), Dupuis, J. (Josée), Hall, I.P. (Ian), Brusselle, G.G. (Guy), Tobin, M.D. (Martin), London, S.J. (Stephanie), Loth, D.W. (Daan), Artigas, M.S., Gharib, S.A. (Sina), Wain, L.V. (Louise), Franceschini, N. (Nora), Koch, B. (Beate), Pottinger, T.D. (Tess), Smith, A.V. (Davey), Duan, Q. (Qing), Oldmeadow, C. (Christopher), Lee, M.K. (Mi Kyeong), Strachan, D.P. (David), James, A.L. (Alan), Huffman, J.E. (Jennifer), Vitart, V. (Veronique), Ramasamy, A. (Adaikalavan), Wareham, N.J. (Nick), Kaprio, J. (Jaakko), Wang, X.-Q. (Xin-Qun), Trochet, H. (Holly), Kähönen, M. (Mika), Flexeder, C. (Claudia), Albrecht, E. (Eva), Lopez, L.M. (Lorna), Thyagarajan, B. (Bharat), Alves, A.C. (Alexessander Couto), Enroth, S. (Stefan), Omenaas, E. (Ernst), Joshi, P.K. (Peter), Fall, M. (Magnus), Viñuela, A. (Ana), Launer, L.J. (Lenore), Loehr, L.R. (Laura), Fornage, M. (Myriam), Li, G. (Guo), Wilk, J.B. (Jemma), Tang, W. (Wenbo), Manichaikul, A. (Ani), Lahousse, L. (Lies), Harris, T.B. (Tamara), North, K.E. (Kari), Rudnicka, A.R. (Alicja), Hui, J. (Jennie), Gu, X. (Xiangjun), Lumley, T. (Thomas), Wright, A.F. (Alan), Hastie, N. (Nick), Campbell, S. (Susan), Kumar, R. (Rajesh), Pin, I. (Isabelle), Scott, R.A. (Robert), Pietilainen, K.H. (Kirsi Hannele), Surakka, I. (Ida), Liu, Y. (YongMei), Holliday, E.G. (Elizabeth), Schulz, H. (Holger), Heinrich, J. (Joachim), Davies, G. (Gail), Vonk, J.M. (Judith), Wojczynski, M.K. (Mary ), Pouta, A. (Anneli), Johansson, A. (Åsa), Wild, S.H. (Sarah), Ingelsson, E. (Erik), Rivadeneira Ramirez, F. (Fernando), Völzke, H. (Henry), Hysi, P.G. (Pirro), Eiriksdottir, G. (Gudny), Morrison, A.C. (Alanna), Rotter, J.I. (Jerome), Gao, W. (Wei), Postma, D.S. (Dirkje), White, W.B. (Wendy), Rich, S.S. (Stephen), Hofman, A. (Albert), Aspelund, T. (Thor), Couper, D. (David), Smith, L.J. (Lewis), Psaty, B.M. (Bruce), Lohman, K. (Kurt), Burchard, E.G. (Esteban), Uitterlinden, A.G. (André), Garcia, M. (Melissa), Joubert, B.R. (Bonnie), McArdle, W.L. (Wendy), Musk, A.W. (Arthur), Hansel, C.R.W. (Christian), Heckbert, S.R. (Susan), Zgaga, L. (Lina), Meurs, J.B.J. (Joyce) van, Navarro, P. (Pau), Rudan, I. (Igor), Oh, Y.-M. (Yeon-Mok), Redline, S. (Susan), Jarvis, D.L. (Deborah), Zhao, J.H. (Jing Hua), Rantanen, T. (Taina), O'Connor, G.T. (George), Ripatti, S. (Samuli), Scott, R.J. (Rodney), Karrasch, S. (Stefan), Grallert, H. (Harald), Gaddis, N.C. (Nathan), Starr, J.M. (John), Wijmenga, C. (Cisca), Minster, R.L. (Ryan), Lederer, C.W. (Carsten), Pekkanen, J. (Juha), Gyllensten, U. (Ulf), Campbell, H. (Harry), Morris, A.P. (Andrew), Gläser, S. (Sven), Hammond, C.J. (Christopher), Burkart, K.M. (Kristin), Beilby, J.P. (John), Kritchevsky, S.B. (Stephen), Gudnason, V. (Vilmundur), Hancock, D.B. (Dana), Williams, O.D. (Dale), Polasek, O. (Ozren), Zemunik, T. (Tatijana), Kolcic, I. (Ivana), Petrini, M.F. (Marcy), Jong, K.T. (Kim) de, Wjst, M. (Matthias), Kim, W.H. (Woo), Porteous, D.J. (David J.), Scotland, G. (Generation), Smith, B.H. (Blair), Viljanen, A. (Anne), Heliovaara, M. (Markku), Attia, J. (John), Sayers, I. (Ian), Hampel, R. (Regina), Gieger, C. (Christian), Deary, I.J. (Ian), Boezen, H.M. (Marike), Newman, A.B. (Anne), Jarvelin, M.-R. (Marjo-Riitta), Wilson, J.F. (James), Lind, L. (Lars), Stricker, B.H.Ch. (Bruno), Teumer, A. (Alexander), Spector, T.D. (Timothy), Melén, E. (Erik), Peters, M.J. (Marjolein), Lange, L.A. (Leslie), Barr, R.G. (Graham), Bracke, K.R. (Ken), Verhamme, F.M. (Fien), Sung, J. (Joohon), Hiemstra, P.S. (Pieter), Cassano, P.A. (Patricia), Sood, A. (Akshay), Hayward, C. (Caroline), Dupuis, J. (Josée), Hall, I.P. (Ian), Brusselle, G.G. (Guy), Tobin, M.D. (Martin), and London, S.J. (Stephanie)
Abstract: Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10-8) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.
Published: 2014
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18. Genome-wide association analysis identifies six new loci associated with forced vital capacity

Author: Loth, D.W. (Daan), Artigas, M.S., Gharib, S.A. (Sina), Wain, L.V. (Louise), Franceschini, N. (Nora), Koch, B. (Beate), Pottinger, T.D. (Tess), Smith, A.V. (Davey), Duan, Q. (Qing), Oldmeadow, C. (Christopher), Lee, M.K. (Mi Kyeong), Strachan, D.P. (David), James, A.L. (Alan), Huffman, J.E. (Jennifer), Vitart, V. (Veronique), Ramasamy, A. (Adaikalavan), Wareham, N.J. (Nick), Kaprio, J. (Jaakko), Wang, X.-Q. (Xin-Qun), Trochet, H. (Holly), Kähönen, M. (Mika), Flexeder, C. (Claudia), Albrecht, E. (Eva), Lopez, L.M. (Lorna), Thyagarajan, B. (Bharat), Alves, A.C. (Alexessander Couto), Enroth, S. (Stefan), Omenaas, E. (Ernst), Joshi, P.K. (Peter), Fall, M. (Magnus), Viñuela, A. (Ana), Launer, L.J. (Lenore), Loehr, L.R. (Laura), Fornage, M. (Myriam), Li, G. (Guo), Wilk, J.B. (Jemma), Tang, W. (Wenbo), Manichaikul, A. (Ani), Lahousse, L. (Lies), Harris, T.B. (Tamara), North, K.E. (Kari), Rudnicka, A.R. (Alicja), Hui, J. (Jennie), Gu, X. (Xiangjun), Lumley, T. (Thomas), Wright, A.F. (Alan), Hastie, N. (Nick), Campbell, S. (Susan), Kumar, R. (Rajesh), Pin, I. (Isabelle), Scott, R.A. (Robert), Pietilainen, K.H. (Kirsi Hannele), Surakka, I. (Ida), Liu, Y. (YongMei), Holliday, E.G. (Elizabeth), Schulz, H. (Holger), Heinrich, J. (Joachim), Davies, G. (Gail), Vonk, J.M. (Judith), Wojczynski, M.K. (Mary ), Pouta, A. (Anneli), Johansson, A. (Åsa), Wild, S.H. (Sarah), Ingelsson, E. (Erik), Rivadeneira Ramirez, F. (Fernando), Völzke, H. (Henry), Hysi, P.G. (Pirro), Eiriksdottir, G. (Gudny), Morrison, A.C. (Alanna), Rotter, J.I. (Jerome), Gao, W. (Wei), Postma, D.S. (Dirkje), White, W.B. (Wendy), Rich, S.S. (Stephen), Hofman, A. (Albert), Aspelund, T. (Thor), Couper, D. (David), Smith, L.J. (Lewis), Psaty, B.M. (Bruce), Lohman, K. (Kurt), Burchard, E.G. (Esteban), Uitterlinden, A.G. (André), Garcia, M. (Melissa), Joubert, B.R. (Bonnie), McArdle, W.L. (Wendy), Musk, A.W. (Arthur), Hansel, C.R.W. (Christian), Heckbert, S.R. (Susan), Zgaga, L. (Lina), Meurs, J.B.J. (Joyce) van, Navarro, P. (Pau), Rudan, I. (Igor), Oh, Y.-M. (Yeon-Mok), Redline, S. (Susan), Jarvis, D.L. (Deborah), Zhao, J.H. (Jing Hua), Rantanen, T. (Taina), O'Connor, G.T. (George), Ripatti, S. (Samuli), Scott, R.J. (Rodney), Karrasch, S. (Stefan), Grallert, H. (Harald), Gaddis, N.C. (Nathan), Starr, J.M. (John), Wijmenga, C. (Cisca), Minster, R.L. (Ryan), Lederer, C.W. (Carsten), Pekkanen, J. (Juha), Gyllensten, U. (Ulf), Campbell, H. (Harry), Morris, A.P. (Andrew), Gläser, S. (Sven), Hammond, C.J. (Christopher), Burkart, K.M. (Kristin), Beilby, J.P. (John), Kritchevsky, S.B. (Stephen), Gudnason, V. (Vilmundur), Hancock, D.B. (Dana), Williams, O.D. (Dale), Polasek, O. (Ozren), Zemunik, T. (Tatijana), Kolcic, I. (Ivana), Petrini, M.F. (Marcy), Jong, K.T. (Kim) de, Wjst, M. (Matthias), Kim, W.H. (Woo), Porteous, D.J. (David J.), Scotland, G. (Generation), Smith, B.H. (Blair), Viljanen, A. (Anne), Heliovaara, M. (Markku), Attia, J. (John), Sayers, I. (Ian), Hampel, R. (Regina), Gieger, C. (Christian), Deary, I.J. (Ian), Boezen, H.M. (Marike), Newman, A.B. (Anne), Jarvelin, M.-R. (Marjo-Riitta), Wilson, J.F. (James), Lind, L. (Lars), Stricker, B.H.Ch. (Bruno), Teumer, A. (Alexander), Spector, T.D. (Timothy), Melén, E. (Erik), Peters, M.J. (Marjolein), Lange, L.A. (Leslie), Barr, R.G. (Graham), Bracke, K.R. (Ken), Verhamme, F.M. (Fien), Sung, J. (Joohon), Hiemstra, P.S. (Pieter), Cassano, P.A. (Patricia), Sood, A. (Akshay), Hayward, C. (Caroline), Dupuis, J. (Josée), Hall, I.P. (Ian), Brusselle, G.G. (Guy), Tobin, M.D. (Martin), London, S.J. (Stephanie), Loth, D.W. (Daan), Artigas, M.S., Gharib, S.A. (Sina), Wain, L.V. (Louise), Franceschini, N. (Nora), Koch, B. (Beate), Pottinger, T.D. (Tess), Smith, A.V. (Davey), Duan, Q. (Qing), Oldmeadow, C. (Christopher), Lee, M.K. (Mi Kyeong), Strachan, D.P. (David), James, A.L. (Alan), Huffman, J.E. (Jennifer), Vitart, V. (Veronique), Ramasamy, A. (Adaikalavan), Wareham, N.J. (Nick), Kaprio, J. (Jaakko), Wang, X.-Q. (Xin-Qun), Trochet, H. (Holly), Kähönen, M. (Mika), Flexeder, C. (Claudia), Albrecht, E. (Eva), Lopez, L.M. (Lorna), Thyagarajan, B. (Bharat), Alves, A.C. (Alexessander Couto), Enroth, S. (Stefan), Omenaas, E. (Ernst), Joshi, P.K. (Peter), Fall, M. (Magnus), Viñuela, A. (Ana), Launer, L.J. (Lenore), Loehr, L.R. (Laura), Fornage, M. (Myriam), Li, G. (Guo), Wilk, J.B. (Jemma), Tang, W. (Wenbo), Manichaikul, A. (Ani), Lahousse, L. (Lies), Harris, T.B. (Tamara), North, K.E. (Kari), Rudnicka, A.R. (Alicja), Hui, J. (Jennie), Gu, X. (Xiangjun), Lumley, T. (Thomas), Wright, A.F. (Alan), Hastie, N. (Nick), Campbell, S. (Susan), Kumar, R. (Rajesh), Pin, I. (Isabelle), Scott, R.A. (Robert), Pietilainen, K.H. (Kirsi Hannele), Surakka, I. (Ida), Liu, Y. (YongMei), Holliday, E.G. (Elizabeth), Schulz, H. (Holger), Heinrich, J. (Joachim), Davies, G. (Gail), Vonk, J.M. (Judith), Wojczynski, M.K. (Mary ), Pouta, A. (Anneli), Johansson, A. (Åsa), Wild, S.H. (Sarah), Ingelsson, E. (Erik), Rivadeneira Ramirez, F. (Fernando), Völzke, H. (Henry), Hysi, P.G. (Pirro), Eiriksdottir, G. (Gudny), Morrison, A.C. (Alanna), Rotter, J.I. (Jerome), Gao, W. (Wei), Postma, D.S. (Dirkje), White, W.B. (Wendy), Rich, S.S. (Stephen), Hofman, A. (Albert), Aspelund, T. (Thor), Couper, D. (David), Smith, L.J. (Lewis), Psaty, B.M. (Bruce), Lohman, K. (Kurt), Burchard, E.G. (Esteban), Uitterlinden, A.G. (André), Garcia, M. (Melissa), Joubert, B.R. (Bonnie), McArdle, W.L. (Wendy), Musk, A.W. (Arthur), Hansel, C.R.W. (Christian), Heckbert, S.R. (Susan), Zgaga, L. (Lina), Meurs, J.B.J. (Joyce) van, Navarro, P. (Pau), Rudan, I. (Igor), Oh, Y.-M. (Yeon-Mok), Redline, S. (Susan), Jarvis, D.L. (Deborah), Zhao, J.H. (Jing Hua), Rantanen, T. (Taina), O'Connor, G.T. (George), Ripatti, S. (Samuli), Scott, R.J. (Rodney), Karrasch, S. (Stefan), Grallert, H. (Harald), Gaddis, N.C. (Nathan), Starr, J.M. (John), Wijmenga, C. (Cisca), Minster, R.L. (Ryan), Lederer, C.W. (Carsten), Pekkanen, J. (Juha), Gyllensten, U. (Ulf), Campbell, H. (Harry), Morris, A.P. (Andrew), Gläser, S. (Sven), Hammond, C.J. (Christopher), Burkart, K.M. (Kristin), Beilby, J.P. (John), Kritchevsky, S.B. (Stephen), Gudnason, V. (Vilmundur), Hancock, D.B. (Dana), Williams, O.D. (Dale), Polasek, O. (Ozren), Zemunik, T. (Tatijana), Kolcic, I. (Ivana), Petrini, M.F. (Marcy), Jong, K.T. (Kim) de, Wjst, M. (Matthias), Kim, W.H. (Woo), Porteous, D.J. (David J.), Scotland, G. (Generation), Smith, B.H. (Blair), Viljanen, A. (Anne), Heliovaara, M. (Markku), Attia, J. (John), Sayers, I. (Ian), Hampel, R. (Regina), Gieger, C. (Christian), Deary, I.J. (Ian), Boezen, H.M. (Marike), Newman, A.B. (Anne), Jarvelin, M.-R. (Marjo-Riitta), Wilson, J.F. (James), Lind, L. (Lars), Stricker, B.H.Ch. (Bruno), Teumer, A. (Alexander), Spector, T.D. (Timothy), Melén, E. (Erik), Peters, M.J. (Marjolein), Lange, L.A. (Leslie), Barr, R.G. (Graham), Bracke, K.R. (Ken), Verhamme, F.M. (Fien), Sung, J. (Joohon), Hiemstra, P.S. (Pieter), Cassano, P.A. (Patricia), Sood, A. (Akshay), Hayward, C. (Caroline), Dupuis, J. (Josée), Hall, I.P. (Ian), Brusselle, G.G. (Guy), Tobin, M.D. (Martin), and London, S.J. (Stephanie)
Abstract: Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10-8) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.
Published: 2014
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19. Drug-gene interactions and the search for missing heritability: a cross-sectional pharmacogenomics study of the QT interval

Author: Avery, C.L., Sitlani, C.M. (Colleen), Arking, D.E. (Dan), Arnett, D.K. (Donna), Bis, J.C. (Joshua), Boerwinkle, E.A. (Eric), Buckley, B.M. (Brendan M.), Chen, Y.-D.I. (Ida), Craen, A.J. (Anton) de, Eijgelsheim, M. (Mark), Enquobahrie, D., Evans, D.S. (Daniel), Ford, I. (Ian), Garcia, M. (Melissa), Gudnason, V. (Vilmundur), Harris, T.B. (Tamara), Heckbert, S.R. (Susan), Hochner, H., Hofman, A. (Albert), Hsueh, W.C., Isaacs, A.J. (Aaron), Jukema, J.W. (Jan Wouter), Knekt, P., Kors, J.A. (Jan), Krijthe, B.P. (Bouwe), Kristiansson, K. (Kati), Laaksonen, M.A. (Maarit), Liu, Y. (Ya), Li, X. (Xuhang), MacFarlane, P.W. (Peter), Newton-Cheh, C. (Christopher), Nieminen, M.S. (Markku), Oostra, B.A. (Ben), Peloso, G.M. (Gina), Porthan, K. (Kimmo), Rice, K.M. (Kenneth), Rivadeneira Ramirez, F. (Fernando), Rotter, J.I. (Jerome), Salomaa, V. (Veikko), Sattar, N. (Naveed), Siscovick, D.S. (David), Slagboom, P.E. (Eline), Smith, A.V. (Albert Vernon), Sotoodehnia, N. (Nona), Stott, D.J. (David. J.), Stricker, B.H.Ch. (Bruno), Stürmer, T., Trompet, S. (Stella), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Westendorp, R.G.J. (Rudi), Witteman, J.C.M. (Jacqueline), Whitsel, E.A. (Eric), Psaty, B.M. (Bruce), Avery, C.L., Sitlani, C.M. (Colleen), Arking, D.E. (Dan), Arnett, D.K. (Donna), Bis, J.C. (Joshua), Boerwinkle, E.A. (Eric), Buckley, B.M. (Brendan M.), Chen, Y.-D.I. (Ida), Craen, A.J. (Anton) de, Eijgelsheim, M. (Mark), Enquobahrie, D., Evans, D.S. (Daniel), Ford, I. (Ian), Garcia, M. (Melissa), Gudnason, V. (Vilmundur), Harris, T.B. (Tamara), Heckbert, S.R. (Susan), Hochner, H., Hofman, A. (Albert), Hsueh, W.C., Isaacs, A.J. (Aaron), Jukema, J.W. (Jan Wouter), Knekt, P., Kors, J.A. (Jan), Krijthe, B.P. (Bouwe), Kristiansson, K. (Kati), Laaksonen, M.A. (Maarit), Liu, Y. (Ya), Li, X. (Xuhang), MacFarlane, P.W. (Peter), Newton-Cheh, C. (Christopher), Nieminen, M.S. (Markku), Oostra, B.A. (Ben), Peloso, G.M. (Gina), Porthan, K. (Kimmo), Rice, K.M. (Kenneth), Rivadeneira Ramirez, F. (Fernando), Rotter, J.I. (Jerome), Salomaa, V. (Veikko), Sattar, N. (Naveed), Siscovick, D.S. (David), Slagboom, P.E. (Eline), Smith, A.V. (Albert Vernon), Sotoodehnia, N. (Nona), Stott, D.J. (David. J.), Stricker, B.H.Ch. (Bruno), Stürmer, T., Trompet, S. (Stella), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Westendorp, R.G.J. (Rudi), Witteman, J.C.M. (Jacqueline), Whitsel, E.A. (Eric), and Psaty, B.M. (Bruce)
Abstract: Variability in response to drug use is common and heritable, suggesting that genome-wide pharmacogenomics studies may help explain the 'missing heritability' of complex traits. Here, we describe four independent analyses in 33 781 participants of European ancestry from 10 cohorts that were designed to identify genetic variants modifying the effects of drugs on QT interval duration (QT). Each analysis cross-sectionally examined four therapeutic classes: thiazide diuretics (prevalence of use=13.0%), tri/tetracyclic antidepressants (2.6%), sulfonylurea hypoglycemic agents (2.9%) and QT-prolonging drugs as classified by the University of Arizona Center for Education and Research on Therapeutics (4.4%). Drug-gene interactions were estimated using covariable-adjusted linear regression and results were combined with fixed-effects meta-analysis. Although drug-single-nucleotide polymorphism (SNP) interactions were biologically plausible and variables were well-measured, findings from the four cross-sectional meta-analyses were null (Pinteraction>5.0 × 10-8). Simulations suggested that additional efforts, including longitudinal modeling to increase statistical power, are likely needed to identify potentially important pharmacogenomic effects.The Pharmacogenomics Journal advance online publication, 5 March 2013; doi:10.1038/tpj.2013.4.
Published: 2014
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20. Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins

Author: Postmus, D. (Douwe), Trompet, S. (Stella), Deshmukh, H. (Harshal), Barnes, M.J. (Michael), Li, X. (Xiaohui), Warren, H. (Helen), Chasman, D.I. (Daniel), Zhou, K. (Kaixin), Arsenault, B.J. (Benoit J.), Donnelly, L.A. (Louise), Wiggins, K.L. (Kerri), Avery, C.L., Griffin, P. (Paula), Feng, Q. (Qiping), Taylor, K.D. (Kent), Li, G. (Guo), Evans, D.S. (Daniel), Smith, A.V. (Davey), Keyser, C.E. (Catherina Elisabeth) de, Johnson, A.D. (Andrew), Craen, A.J. (Anton) de, Stott, D.J. (David. J.), Buckley, B.M. (Brendan M.), Ford, I., Westendorp, R.G.J. (Rudi), Slagboom, P.E. (Eline), Sattar, N. (Naveed), Munroe, P. (Patricia), Sever, P. (Peter), Poulter, N.R. (Neil), Stanton, A. (Alice), Shields, D.C. (Denis C.), O'Brien, E. (Eoin), Shaw-Hawkins, S. (Sue), Chen, Y.-D.I. (Ida), Nickerson, D.A. (Deborah), Smith, J.D. (Joshua D.), Dubé, G.P. (Gregory), Boekholdt, S.M. (Matthijs), Hovingh, G.K. (Kees), Kastelein, J.J.P. (John), Mckeigue, P.M. (Paul), Betteridge, J. (John), Neil, A. (Andrew), Durrington, P.N. (Paul), Doney, A.S.F. (Alex), Carr, F. (Fiona), Morris, A.D. (Andrew), McCarthy, M.I. (Mark), Groop, L. (Leif), Ahlqvist, E. (Emma), Barroso, I.E. (Inês), Blackwell, K.L. (Kimberly), Bramon, E. (Elvira), Brown, M.A. (Matthew), Casas, J.P. (Juan), Corvin, A. (Aiden), Deloukas, P. (Panagiotis), Duncanson, A. (Audrey), Jankowski, J.A. (Janusz Antoni), Markus, H.S. (Hugh), Mathew, C.G. (Christopher G.), Palmer, C.N.A. (Colin), Plomin, R. (Robert), Rautanen, A. (Anna), Sawcer, S.J. (Stephen), Trembath, R.C. (Richard), Viswanathan, A.C. (Ananth), Wood, N.W. (Nicholas), Spencer, C.C.A. (Chris C.), Band, G. (Gavin), Bellenguez, C. (Céline), Freeman, C. (Colin), Hellenthal, F.A., Giannoulatou, E. (Eleni), Pirinen, M. (Matti), Pearson, R. (Ruth), Strange, A. (Amy), Su, Z. (Zhan), Vukcevic, D. (Damjan), Donnelly, P. (Peter), Langford, C. (Cordelia), Hunt, S.E. (Sarah), Edkins, T. (Ted), Gwilliam, R. (Rhian), Blackburn, H. (Hannah), Bumpstead, S. (Suzannah), Dronov, S. (Serge), Gillman, M. (Matthew), Gray, E. (Emma), Hammond, N. (Naomi), Jayakumar, A. (Alagurevathi), McCann, O.T. (Owen), Liddle, J. (Jennifer), Potter, S.C. (Simon), Ravindrarajah, R. (Radhi), Ricketts, M. (Michelle), Waller, M. (Matthew), Weston, P. (Paul), Widaa, S. (Sara), Whittaker, P. (Pamela), Bis, J.C. (Joshua), Rice, K.M. (Kenneth), Smith, N.L. (Nicholas), Lumley, T. (Thomas), Whitsel, E.A. (Eric), Stürmer, T., Boerwinkle, E.A. (Eric), Ngwa, J.S., O'Donnell, C.J. (Christopher J.), Vasan, R.S. (Ramachandran Srini), Wei, W.-Q. (Wei-Qi), Wilke, R.A. (Russell A.), Liu, C.-T. (Ching-Ti), Sun, F. (Fangui), Guo, X. (Xiuqing), Heckbert, S.R. (Susan), Post, W. (Wendy), Sotoodehnia, N. (Nona), Arnold, A.M. (Alice), Stafford, J.M. (Jeanette M.), Ding, J. (Jingzhong), Herrington, D.M. (David), Kritchevsky, S.B. (Stephen), Eiriksdottir, G. (Gudny), Launer, L.J. (Lenore), Harris, T.B. (Tamara), Chu, A.Y. (Audrey), Giulianini, F. (Franco), MacFadyen, J.G. (Jean G.), Barratt, B.J. (Bryan J.), Nyberg, F. (Fredrik), Stricker, B.H.Ch. (Bruno), Uitterlinden, A.G. (André), Hofman, A. (Albert), Rivadeneira Ramirez, F. (Fernando), Emilsson, V. (Valur), Franco, O.H. (Oscar), Ridker, P.M. (Paul), Gudnason, V. (Vilmundur), Liu, Y. (YongMei), Denny, J.C. (Joshua C.), Ballantyne, C. (Christie), Rotter, J.I. (Jerome I.), Cupples, L.A. (Adrienne), Psaty, B.M. (Bruce), Tardif, J.-C. (Jean-Claude), Colhoun, H.M. (H.), Hitman, G.A. (Graham), Krauss, R.M. (Ronald), Jukema, J.W. (Jan Wouter), Caulfield, M. (Mark), Postmus, D. (Douwe), Trompet, S. (Stella), Deshmukh, H. (Harshal), Barnes, M.J. (Michael), Li, X. (Xiaohui), Warren, H. (Helen), Chasman, D.I. (Daniel), Zhou, K. (Kaixin), Arsenault, B.J. (Benoit J.), Donnelly, L.A. (Louise), Wiggins, K.L. (Kerri), Avery, C.L., Griffin, P. (Paula), Feng, Q. (Qiping), Taylor, K.D. (Kent), Li, G. (Guo), Evans, D.S. (Daniel), Smith, A.V. (Davey), Keyser, C.E. (Catherina Elisabeth) de, Johnson, A.D. (Andrew), Craen, A.J. (Anton) de, Stott, D.J. (David. J.), Buckley, B.M. (Brendan M.), Ford, I., Westendorp, R.G.J. (Rudi), Slagboom, P.E. (Eline), Sattar, N. (Naveed), Munroe, P. (Patricia), Sever, P. (Peter), Poulter, N.R. (Neil), Stanton, A. (Alice), Shields, D.C. (Denis C.), O'Brien, E. (Eoin), Shaw-Hawkins, S. (Sue), Chen, Y.-D.I. (Ida), Nickerson, D.A. (Deborah), Smith, J.D. (Joshua D.), Dubé, G.P. (Gregory), Boekholdt, S.M. (Matthijs), Hovingh, G.K. (Kees), Kastelein, J.J.P. (John), Mckeigue, P.M. (Paul), Betteridge, J. (John), Neil, A. (Andrew), Durrington, P.N. (Paul), Doney, A.S.F. (Alex), Carr, F. (Fiona), Morris, A.D. (Andrew), McCarthy, M.I. (Mark), Groop, L. (Leif), Ahlqvist, E. (Emma), Barroso, I.E. (Inês), Blackwell, K.L. (Kimberly), Bramon, E. (Elvira), Brown, M.A. (Matthew), Casas, J.P. (Juan), Corvin, A. (Aiden), Deloukas, P. (Panagiotis), Duncanson, A. (Audrey), Jankowski, J.A. (Janusz Antoni), Markus, H.S. (Hugh), Mathew, C.G. (Christopher G.), Palmer, C.N.A. (Colin), Plomin, R. (Robert), Rautanen, A. (Anna), Sawcer, S.J. (Stephen), Trembath, R.C. (Richard), Viswanathan, A.C. (Ananth), Wood, N.W. (Nicholas), Spencer, C.C.A. (Chris C.), Band, G. (Gavin), Bellenguez, C. (Céline), Freeman, C. (Colin), Hellenthal, F.A., Giannoulatou, E. (Eleni), Pirinen, M. (Matti), Pearson, R. (Ruth), Strange, A. (Amy), Su, Z. (Zhan), Vukcevic, D. (Damjan), Donnelly, P. (Peter), Langford, C. (Cordelia), Hunt, S.E. (Sarah), Edkins, T. (Ted), Gwilliam, R. (Rhian), Blackburn, H. (Hannah), Bumpstead, S. (Suzannah), Dronov, S. (Serge), Gillman, M. (Matthew), Gray, E. (Emma), Hammond, N. (Naomi), Jayakumar, A. (Alagurevathi), McCann, O.T. (Owen), Liddle, J. (Jennifer), Potter, S.C. (Simon), Ravindrarajah, R. (Radhi), Ricketts, M. (Michelle), Waller, M. (Matthew), Weston, P. (Paul), Widaa, S. (Sara), Whittaker, P. (Pamela), Bis, J.C. (Joshua), Rice, K.M. (Kenneth), Smith, N.L. (Nicholas), Lumley, T. (Thomas), Whitsel, E.A. (Eric), Stürmer, T., Boerwinkle, E.A. (Eric), Ngwa, J.S., O'Donnell, C.J. (Christopher J.), Vasan, R.S. (Ramachandran Srini), Wei, W.-Q. (Wei-Qi), Wilke, R.A. (Russell A.), Liu, C.-T. (Ching-Ti), Sun, F. (Fangui), Guo, X. (Xiuqing), Heckbert, S.R. (Susan), Post, W. (Wendy), Sotoodehnia, N. (Nona), Arnold, A.M. (Alice), Stafford, J.M. (Jeanette M.), Ding, J. (Jingzhong), Herrington, D.M. (David), Kritchevsky, S.B. (Stephen), Eiriksdottir, G. (Gudny), Launer, L.J. (Lenore), Harris, T.B. (Tamara), Chu, A.Y. (Audrey), Giulianini, F. (Franco), MacFadyen, J.G. (Jean G.), Barratt, B.J. (Bryan J.), Nyberg, F. (Fredrik), Stricker, B.H.Ch. (Bruno), Uitterlinden, A.G. (André), Hofman, A. (Albert), Rivadeneira Ramirez, F. (Fernando), Emilsson, V. (Valur), Franco, O.H. (Oscar), Ridker, P.M. (Paul), Gudnason, V. (Vilmundur), Liu, Y. (YongMei), Denny, J.C. (Joshua C.), Ballantyne, C. (Christie), Rotter, J.I. (Jerome I.), Cupples, L.A. (Adrienne), Psaty, B.M. (Bruce), Tardif, J.-C. (Jean-Claude), Colhoun, H.M. (H.), Hitman, G.A. (Graham), Krauss, R.M. (Ronald), Jukema, J.W. (Jan Wouter), and Caulfield, M. (Mark)
Published: 2014
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21. B-type natriuretic peptide and C-reactive protein in the prediction of atrial fibrillation risk: the CHARGE-AF Consortium of community-based cohort studies

Author: Sinner, M.F. (Moritz), Stepas, K.A. (Katherine A.), Moser, C.B. (Carlee B.), Krijthe, B.P. (Bouwe), Aspelund, T. (Thor), Sotoodehnia, N. (Nona), Fontes, M. (Michel), Janssens, A.C.J.W. (Cécile), Kronmal, R.A. (Richard), Magnani, J.W. (Jared), Witteman, J.C.M. (Jacqueline), Chamberlain, A.M. (Alanna), Lubitz, S.A. (Steven), Schnabel, R. (Renate), Vasan, R.S. (Ramachandran S.), Wang, T.J. (Thomas), Agarwal, S.K. (Sunil), McManus, D.D. (David), Franco, O.H. (Oscar), Yin, X. (Xiaoyan), Larson, M.G. (Martin), Burke, G.L. (Greg), Launer, L.J. (Lenore), Hofman, A. (Albert), Levy, D. (Daniel), Gottdiener, J.S. (John), Kääb, S. (Stefan), Couper, D.J. (David), Harris, T.B. (Tamara), Astor, B.C. (Brad), Ballantyne, C. (Christie), Hoogeveen, R.C. (Ron), Arai, T. (Takashi), Soliman, E.Z. (Elsayed Z.), Ellinor, P.T. (Patrick), Stricker, B.H.Ch. (Bruno), Gudnason, V. (Vilmundur), Heckbert, S.R. (Susan), Pencina, M. (Michael), Benjamin, E.J. (Emelia), Alonso, A. (Alvaro), Sinner, M.F. (Moritz), Stepas, K.A. (Katherine A.), Moser, C.B. (Carlee B.), Krijthe, B.P. (Bouwe), Aspelund, T. (Thor), Sotoodehnia, N. (Nona), Fontes, M. (Michel), Janssens, A.C.J.W. (Cécile), Kronmal, R.A. (Richard), Magnani, J.W. (Jared), Witteman, J.C.M. (Jacqueline), Chamberlain, A.M. (Alanna), Lubitz, S.A. (Steven), Schnabel, R. (Renate), Vasan, R.S. (Ramachandran S.), Wang, T.J. (Thomas), Agarwal, S.K. (Sunil), McManus, D.D. (David), Franco, O.H. (Oscar), Yin, X. (Xiaoyan), Larson, M.G. (Martin), Burke, G.L. (Greg), Launer, L.J. (Lenore), Hofman, A. (Albert), Levy, D. (Daniel), Gottdiener, J.S. (John), Kääb, S. (Stefan), Couper, D.J. (David), Harris, T.B. (Tamara), Astor, B.C. (Brad), Ballantyne, C. (Christie), Hoogeveen, R.C. (Ron), Arai, T. (Takashi), Soliman, E.Z. (Elsayed Z.), Ellinor, P.T. (Patrick), Stricker, B.H.Ch. (Bruno), Gudnason, V. (Vilmundur), Heckbert, S.R. (Susan), Pencina, M. (Michael), Benjamin, E.J. (Emelia), and Alonso, A. (Alvaro)
Abstract: AIMS: B-type natriuretic peptide (BNP) and C-reactive protein (CRP) predict atrial fibrillation (AF) risk. However, their risk stratification abilities in the broad community remain uncertain. We sought to improve risk stratification for AF using biomarker information.METHODS AND RESULTS: We ascertained AF incidence in 18 556 Whites and African Americans from the Atherosclerosis Risk in Communities Study (ARIC, n=10 675), Cardiovascular Health Study (CHS, n = 5043), and Framingham Heart Study (FHS, n = 2838), followed for 5 years (prediction horizon). We added BNP (ARIC/CHS: N-terminal pro
Published: 2014
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22. Novel genetic markers associate with atrial fibrillation risk in Europeans and Japanese

Author: Lubitz, S.A. (Steven), Lunetta, K.L. (Kathryn), Lin, H. (Honghuang), Arking, D.E. (Dan), Trompet, S. (Stella), Li, G. (Guo), Krijthe, B.P. (Bouwe), Chasman, D.I. (Daniel), Barnard, J. (John), Kleber, M.E. (Marcus), Dörr, M. (Marcus), Ozaki, Y. (Yukio), Smith, A.V. (Davey), Müller-Nurasyid, M. (Martina), Walter, S. (Stefan), Agarwal, S.K. (Sunil), Bis, J.C. (Joshua), Brody, J.A. (Jennifer A.), Chen, L. (Lin), Everett, B.M. (Brendan), Ford, I. (Ian), Franco, O.H. (Oscar), Harris, T.B. (Tamara), Hofman, A. (Albert), Kääb, S. (Stefan), Mahida, S. (Saagar), Kathiresan, S. (Sekar), Kubo, M. (Michiaki), Launer, L.J. (Lenore), MacFarlane, P.W. (Peter), Magnani, J.W. (Jared), McKnight, B. (Barbara), McManus, D.D. (David), Peters, A. (Annette), Psaty, B.M. (Bruce), Rose, L.M. (Lynda), Rotter, J.I. (Jerome), Silbernagel, G. (Günther), Smith, J.D. (Jonathan), Sotoodehnia, N. (Nona), Stott, D.J. (David. J.), Taylor, K.D. (Kent), Tomaschitz, A. (Andreas), Tsunoda, T. (Tatsuhiko), Uitterlinden, A.G. (André), Wagoner, D.R. (David) van, Völker, U. (Uwe), Völzke, H. (Henry), Murabito, J. (Joanne), Sinner, M.F. (Moritz), Gudnason, V. (Vilmundur), Felix, S.B. (Stephan), März, W. (Winfried), Chung, M.K. (Mina), Albert, C.M. (Christine), Stricker, B.H.Ch. (Bruno), Tanaka, T. (Toshihiro), Heckbert, S.R. (Susan), Jukema, J.W. (Jan Wouter), Alonso, A. (Alvaro), Benjamin, E.J. (Emelia), Ellinor, P.T. (Patrick), Lubitz, S.A. (Steven), Lunetta, K.L. (Kathryn), Lin, H. (Honghuang), Arking, D.E. (Dan), Trompet, S. (Stella), Li, G. (Guo), Krijthe, B.P. (Bouwe), Chasman, D.I. (Daniel), Barnard, J. (John), Kleber, M.E. (Marcus), Dörr, M. (Marcus), Ozaki, Y. (Yukio), Smith, A.V. (Davey), Müller-Nurasyid, M. (Martina), Walter, S. (Stefan), Agarwal, S.K. (Sunil), Bis, J.C. (Joshua), Brody, J.A. (Jennifer A.), Chen, L. (Lin), Everett, B.M. (Brendan), Ford, I. (Ian), Franco, O.H. (Oscar), Harris, T.B. (Tamara), Hofman, A. (Albert), Kääb, S. (Stefan), Mahida, S. (Saagar), Kathiresan, S. (Sekar), Kubo, M. (Michiaki), Launer, L.J. (Lenore), MacFarlane, P.W. (Peter), Magnani, J.W. (Jared), McKnight, B. (Barbara), McManus, D.D. (David), Peters, A. (Annette), Psaty, B.M. (Bruce), Rose, L.M. (Lynda), Rotter, J.I. (Jerome), Silbernagel, G. (Günther), Smith, J.D. (Jonathan), Sotoodehnia, N. (Nona), Stott, D.J. (David. J.), Taylor, K.D. (Kent), Tomaschitz, A. (Andreas), Tsunoda, T. (Tatsuhiko), Uitterlinden, A.G. (André), Wagoner, D.R. (David) van, Völker, U. (Uwe), Völzke, H. (Henry), Murabito, J. (Joanne), Sinner, M.F. (Moritz), Gudnason, V. (Vilmundur), Felix, S.B. (Stephan), März, W. (Winfried), Chung, M.K. (Mina), Albert, C.M. (Christine), Stricker, B.H.Ch. (Bruno), Tanaka, T. (Toshihiro), Heckbert, S.R. (Susan), Jukema, J.W. (Jan Wouter), Alonso, A. (Alvaro), Benjamin, E.J. (Emelia), and Ellinor, P.T. (Patrick)
Abstract: Objectives This study sought to identify nonredundant atrial fibrillation (AF) genetic susceptibility signals and examine their cumulative relations with AF risk. Background AF-associated loci span broad genomic regions that may contain multiple susceptibility signals. Whether multiple signals exist at AF loci has not been systematically explored. Methods We performed association testing conditioned on the most significant, independently associated genetic markers at 9 established AF loci using 2 complementary techniques in 64,683 individuals of European ancestry (3,869 incident and 3,302 prevalent AF cases). Genetic risk scores were created and tested for association with AF in Europeans and an independent sample of 11,309 individuals of Japanese ancestry (7,916 prevalent AF cases). Results We observed at least 4 distinct AF susceptibility signals on chromosome 4q25 upstream of PITX2, but not at the re
Published: 2014
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23. Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

Author: Arking, D.E. (Dan), Pulit, S.L. (Sara), Crotti, L. (Lia), Harst, P. (Pim) van der, Munroe, P. (Patricia), Koopmann, T.T. (Tamara), Sotoodehnia, N. (Nona), Rossin, E. (Elizabeth), Morley, M. (Michael), Wang, X. (Xinchen), Johnson, A.D. (Andrew), Lundby, A. (Alicia), Gudbjartsson, D.F. (Daniel), Noseworthy, P.A. (Peter), Eijgelsheim, M. (Mark), Bradford, Y. (Yuki), Tarasov, K.V. (Kirill), Dörr, M. (Marcus), Müller-Nurasyid, M. (Martina), Lahtinen, A.M. (Annukka), Nolte, I.M. (Ilja), Smith, A.V. (Davey), Bis, J.C. (Joshua), Isaacs, A.J. (Aaron), Newhouse, S.J. (Stephen), Evans, D.S. (Daniel), Post, W.S. (Wendy S.), Waggott, D. (Daryl), Lyytikäinen, L.-P. (Leo-Pekka), Hicks, A.A. (Andrew), Eisele, L. (Lewin), Ellinghaus, D. (David), Hayward, C. (Caroline), Navarro, P. (Pau), Ulivi, S. (Shelia), Tanaka, T. (Toshiko), Tester, D.J. (David), Chatel, S. (Stéphanie), Gustafsson, S. (Stefan), Kumari, M. (Meena), Morris, R.W. (Richard), Naluai, A.T. (Asa), Padmanabhan, S. (Sandosh), Kluttig, A. (Alexander), Strohmer, B. (Bernhard), Panayiotou, A.G. (Andrie), Torres, M. (Maria), Knoflach, M. (Michael), Hubacek, J.A. (Jaroslav A.), Slowikowski, K. (Kamil), Raychaudhuri, S. (Soumya), Kumar, R.D. (Runjun), Harris, T.B. (Tamara), Launer, L.J. (Lenore), Shuldiner, A.R. (Alan), Alonso, A. (Alvaro), Bader, J.S. (Joel), Ehret, G.B. (Georg), Huang, H. (Hailiang), Kao, W.H.L. (Wen), Strait, J.B. (James), Macfarlane, P.W. (Peter), Brown, M.J. (Morris), Caulfield, M. (Mark), Samani, N.J. (Nilesh), Kronenberg, F. (Florian), Willeit, J. (Johann), Smith, J.G. (J. Gustav), Greiser, K.H. (Karin Halina), Zu Schwabedissen, H.M. (Henriette Meyer), Werdan, K. (Karl), Carella, C. (Cintia), Zelante, L. (Leopoldo), Heckbert, S.R. (Susan), Psaty, B.M. (Bruce), Rotter, J.I. (Jerome), Kolcic, I. (Ivana), Polasek, O. (Ozren), Wright, A.F. (Alan), Griffin, M. (Maura), Daly, M.J. (Mark), Arnar, D.O. (David), Hólm, H. (Hilma), Thorsteinsdottir, U. (Unnur), Denny, J.C. (Joshua), Roden, D.M. (Dan), Zuvich, R.L. (Rebecca), Emilsson, V. (Valur), Plump, A.S. (Andrew), Larson, M.G. (Martin), O'Donnell, C.J. (Christopher), Yin, X. (Xiaoyan), Bobbo, M. (Marco), Adamo, P. (Pio) d', Iorio, A. (Annamaria), Sinagra, G. (Gianfranco), Carracedo, A. (Angel), Cummings, S.R. (Steven), Nalls, M.A. (Michael), Jula, A. (Antti), Kontula, K.K. (Kimmo), Marjamaa, A. (Annukka), Oikarinen, L. (Lasse), Perola, M. (Markus), Porthan, K. (Kimmo), Erbel, R. (Raimund), Hoffmann, P. (Per), Jöckel, K.-H. (Karl-Heinz), Kälsch, H. (Hagen), Nöthen, M.M. (Markus), Hoed, M. (Marcel) den, Loos, R.J.F. (Ruth), Thelle, D.S. (Dag), Gieger, C. (Christian), Meitinger, T. (Thomas), Perz, S. (Siegfried), Peters, A. (Annette), Prucha, H. (Hanna), Sinner, M.F. (Moritz), Waldenberger, M. (Melanie), Boer, R.A. (Rudolf) de, Franke, L. (Lude), Vleuten, P.A. (Pieter) van der, Beckmann, B.M. (Britt), Martens, E. (Eimo), Bardai, A. (Abdennasser), Hofman, N. (Nynke), Wilde, A.A.M. (Arthur), Behr, E.R. (Elijah), Dalageorgou, C. (Chrysoula), Giudicessi, J.R. (John), Medeiros-Domingo, A. (Argelia), Barc, J. (Julien), Kyndt, F. (Florence), Probst, V. (Vincent), Ghidoni, A. (Alice), Insolia, R. (Roberto), Hamilton, R.M. (Robert), Scherer, S.W. (Stephen), Brandimarto, J. (Jeffrey), Margulies, K. (Kenneth), Moravec, C.E. (Christine), Del Greco, F. (Fabiola), Fuchsberger, C. (Christian), O'Connell, J.R. (Jeffery), Lee, W.K. (Wai), Watt, G.C.M. (Graham), Campbell, H. (Harry), Wild, S.H. (Sarah), El Mokhtari, N.E. (Nour), Frey, N. (Norbert), Asselbergs, F.W. (Folkert), Leach, I.M. (Irene Mateo), Navis, G. (Gerjan), Berg, M.P. (Maarten) van den, Veldhuisen, D.J. (Dirk) van, Kellis, M. (Manolis), Krijthe, B.P. (Bouwe), Franco, O.H. (Oscar), Hofman, A. (Albert), Kors, J.A. (Jan), Uitterlinden, A.G. (André), Witteman, J.C.M. (Jacqueline), Kedenko, L. (Lyudmyla), Lamina, C. (Claudia), Oostra, B.A. (Ben), Abecasis, G.R. (Gonçalo), Lakatta, E. (Edward), Mulas, A. (Antonella), Orrù, M. (Marco), Schlessinger, D. (David), Uda, M. (Manuela), Markus, M.R.P. (Marcello R. P.), Völker, U. (Uwe), Snieder, H. (Harold), Spector, T.D. (Timothy), Ärnlöv, J. (Johan), Lind, L. (Lars), Sundstrom, J. (Johan), Syvanen, A.C., Kivimaki, M. (Mika), Kähönen, M. (Mika), Mononen, K. (Kari), Raitakari, O. (Olli), Viikari, J. (Jorma), Adamkova, V. (Vera), Kiechl, S. (Stefan), Brion, M.-J. (Maria), Nicolaides, A.N. (Andrew), Paulweber, B. (Bernhard), Haerting, J. (Johannes), Dominiczak, A. (Anna), Nyberg, F. (Fredrik), Whincup, P.H. (Peter), Hingorani, A. (Aroon), Schott, J.-J. (Jean-Jacques), Bezzina, C.R. (Connie), Ingelsson, E. (Erik), Ferrucci, L. (Luigi), Gasparini, P. (Paolo), Wilson, J.F. (James), Rudan, I. (Igor), Franke, A. (Andre), Mühleisen, T.W. (Thomas), Pramstaller, P.P. (Peter Paul), Lehtimäki, T. (Terho), Paterson, A.D. (Andrew), Parsa, A. (Afshin), Liu, Y. (YongMei), Duijn, C.M. (Cornelia) van, Siscovick, D.S. (David), Gudnason, V. (Vilmundur), Jamshidi, Y. (Yalda), Salomaa, V. (Veikko), Felix, S.B. (Stephan), Sanna, S. (Serena), Ritchie, M.D. (Marylyn), Stricker, B.H.Ch. (Bruno), Zwart, J-A. (John-Anker), Boyer, L.A. (Laurie), Cappola, T.P. (Thomas), Olsen, J.V. (Jesper), Lage, P. (Pedro), Schwartz, P.J. (Peter), Kääb, S. (Stefan), Chakravarti, A. (Aravinda), Ackerman, M. (Margaret), Pfeufer, A. (Arne), Bakker, P.I.W. (Paul) de, Newton-Cheh, C. (Christopher), Arking, D.E. (Dan), Pulit, S.L. (Sara), Crotti, L. (Lia), Harst, P. (Pim) van der, Munroe, P. (Patricia), Koopmann, T.T. (Tamara), Sotoodehnia, N. (Nona), Rossin, E. (Elizabeth), Morley, M. (Michael), Wang, X. (Xinchen), Johnson, A.D. (Andrew), Lundby, A. (Alicia), Gudbjartsson, D.F. (Daniel), Noseworthy, P.A. (Peter), Eijgelsheim, M. (Mark), Bradford, Y. (Yuki), Tarasov, K.V. (Kirill), Dörr, M. (Marcus), Müller-Nurasyid, M. (Martina), Lahtinen, A.M. (Annukka), Nolte, I.M. (Ilja), Smith, A.V. (Davey), Bis, J.C. (Joshua), Isaacs, A.J. (Aaron), Newhouse, S.J. (Stephen), Evans, D.S. (Daniel), Post, W.S. (Wendy S.), Waggott, D. (Daryl), Lyytikäinen, L.-P. (Leo-Pekka), Hicks, A.A. (Andrew), Eisele, L. (Lewin), Ellinghaus, D. (David), Hayward, C. (Caroline), Navarro, P. (Pau), Ulivi, S. (Shelia), Tanaka, T. (Toshiko), Tester, D.J. (David), Chatel, S. (Stéphanie), Gustafsson, S. (Stefan), Kumari, M. (Meena), Morris, R.W. (Richard), Naluai, A.T. (Asa), Padmanabhan, S. (Sandosh), Kluttig, A. (Alexander), Strohmer, B. (Bernhard), Panayiotou, A.G. (Andrie), Torres, M. (Maria), Knoflach, M. (Michael), Hubacek, J.A. (Jaroslav A.), Slowikowski, K. (Kamil), Raychaudhuri, S. (Soumya), Kumar, R.D. (Runjun), Harris, T.B. (Tamara), Launer, L.J. (Lenore), Shuldiner, A.R. (Alan), Alonso, A. (Alvaro), Bader, J.S. (Joel), Ehret, G.B. (Georg), Huang, H. (Hailiang), Kao, W.H.L. (Wen), Strait, J.B. (James), Macfarlane, P.W. (Peter), Brown, M.J. (Morris), Caulfield, M. (Mark), Samani, N.J. (Nilesh), Kronenberg, F. (Florian), Willeit, J. (Johann), Smith, J.G. (J. Gustav), Greiser, K.H. (Karin Halina), Zu Schwabedissen, H.M. (Henriette Meyer), Werdan, K. (Karl), Carella, C. (Cintia), Zelante, L. (Leopoldo), Heckbert, S.R. (Susan), Psaty, B.M. (Bruce), Rotter, J.I. (Jerome), Kolcic, I. (Ivana), Polasek, O. (Ozren), Wright, A.F. (Alan), Griffin, M. (Maura), Daly, M.J. (Mark), Arnar, D.O. (David), Hólm, H. (Hilma), Thorsteinsdottir, U. (Unnur), Denny, J.C. (Joshua), Roden, D.M. (Dan), Zuvich, R.L. (Rebecca), Emilsson, V. (Valur), Plump, A.S. (Andrew), Larson, M.G. (Martin), O'Donnell, C.J. (Christopher), Yin, X. (Xiaoyan), Bobbo, M. (Marco), Adamo, P. (Pio) d', Iorio, A. (Annamaria), Sinagra, G. (Gianfranco), Carracedo, A. (Angel), Cummings, S.R. (Steven), Nalls, M.A. (Michael), Jula, A. (Antti), Kontula, K.K. (Kimmo), Marjamaa, A. (Annukka), Oikarinen, L. (Lasse), Perola, M. (Markus), Porthan, K. (Kimmo), Erbel, R. (Raimund), Hoffmann, P. (Per), Jöckel, K.-H. (Karl-Heinz), Kälsch, H. (Hagen), Nöthen, M.M. (Markus), Hoed, M. (Marcel) den, Loos, R.J.F. (Ruth), Thelle, D.S. (Dag), Gieger, C. (Christian), Meitinger, T. (Thomas), Perz, S. (Siegfried), Peters, A. (Annette), Prucha, H. (Hanna), Sinner, M.F. (Moritz), Waldenberger, M. (Melanie), Boer, R.A. (Rudolf) de, Franke, L. (Lude), Vleuten, P.A. (Pieter) van der, Beckmann, B.M. (Britt), Martens, E. (Eimo), Bardai, A. (Abdennasser), Hofman, N. (Nynke), Wilde, A.A.M. (Arthur), Behr, E.R. (Elijah), Dalageorgou, C. (Chrysoula), Giudicessi, J.R. (John), Medeiros-Domingo, A. (Argelia), Barc, J. (Julien), Kyndt, F. (Florence), Probst, V. (Vincent), Ghidoni, A. (Alice), Insolia, R. (Roberto), Hamilton, R.M. (Robert), Scherer, S.W. (Stephen), Brandimarto, J. (Jeffrey), Margulies, K. (Kenneth), Moravec, C.E. (Christine), Del Greco, F. (Fabiola), Fuchsberger, C. (Christian), O'Connell, J.R. (Jeffery), Lee, W.K. (Wai), Watt, G.C.M. (Graham), Campbell, H. (Harry), Wild, S.H. (Sarah), El Mokhtari, N.E. (Nour), Frey, N. (Norbert), Asselbergs, F.W. (Folkert), Leach, I.M. (Irene Mateo), Navis, G. (Gerjan), Berg, M.P. (Maarten) van den, Veldhuisen, D.J. (Dirk) van, Kellis, M. (Manolis), Krijthe, B.P. (Bouwe), Franco, O.H. (Oscar), Hofman, A. (Albert), Kors, J.A. (Jan), Uitterlinden, A.G. (André), Witteman, J.C.M. (Jacqueline), Kedenko, L. (Lyudmyla), Lamina, C. (Claudia), Oostra, B.A. (Ben), Abecasis, G.R. (Gonçalo), Lakatta, E. (Edward), Mulas, A. (Antonella), Orrù, M. (Marco), Schlessinger, D. (David), Uda, M. (Manuela), Markus, M.R.P. (Marcello R. P.), Völker, U. (Uwe), Snieder, H. (Harold), Spector, T.D. (Timothy), Ärnlöv, J. (Johan), Lind, L. (Lars), Sundstrom, J. (Johan), Syvanen, A.C., Kivimaki, M. (Mika), Kähönen, M. (Mika), Mononen, K. (Kari), Raitakari, O. (Olli), Viikari, J. (Jorma), Adamkova, V. (Vera), Kiechl, S. (Stefan), Brion, M.-J. (Maria), Nicolaides, A.N. (Andrew), Paulweber, B. (Bernhard), Haerting, J. (Johannes), Dominiczak, A. (Anna), Nyberg, F. (Fredrik), Whincup, P.H. (Peter), Hingorani, A. (Aroon), Schott, J.-J. (Jean-Jacques), Bezzina, C.R. (Connie), Ingelsson, E. (Erik), Ferrucci, L. (Luigi), Gasparini, P. (Paolo), Wilson, J.F. (James), Rudan, I. (Igor), Franke, A. (Andre), Mühleisen, T.W. (Thomas), Pramstaller, P.P. (Peter Paul), Lehtimäki, T. (Terho), Paterson, A.D. (Andrew), Parsa, A. (Afshin), Liu, Y. (YongMei), Duijn, C.M. (Cornelia) van, Siscovick, D.S. (David), Gudnason, V. (Vilmundur), Jamshidi, Y. (Yalda), Salomaa, V. (Veikko), Felix, S.B. (Stephan), Sanna, S. (Serena), Ritchie, M.D. (Marylyn), Stricker, B.H.Ch. (Bruno), Zwart, J-A. (John-Anker), Boyer, L.A. (Laurie), Cappola, T.P. (Thomas), Olsen, J.V. (Jesper), Lage, P. (Pedro), Schwartz, P.J. (Peter), Kääb, S. (Stefan), Chakravarti, A. (Aravinda), Ackerman, M. (Margaret), Pfeufer, A. (Arne), Bakker, P.I.W. (Paul) de, and Newton-Cheh, C. (Christopher)
Abstract: The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼ 8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.
Published: 2014
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24. Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function

Author: Tang, W. (Wenbo), Kowgier, M. (Matthew), Loth, D.W. (Daan), Soler Artigas, M. (Maria), Joubert, B.R. (Bonnie), Hodge, E. (Emily), Gharib, S.A. (Sina), Smith, A.V. (Davey), Ruczinski, I. (Ingo), Gudnason, V. (Vilmundur), Mathias, J. (Jasmine), Harris, T.B. (Tamara), Hansel, C.R.W. (Christian), Launer, L.J. (Lenore), Barnes, K.C. (Kathleen), Hansen, J.G. (Joyanna), Albrecht, E. (Eva), Aldrich, M.C. (Melinda), Allerhand, M.M. (Michael), Barr, R.G. (Graham), Brusselle, G.G. (Guy), Couper, D.J. (David), Curjuric, I. (Ivan), Davies, G. (Gail), Deary, I.J. (Ian), Dupuis, J. (Josée), Fall, M. (Magnus), Foy, M. (Millennia), Franceschini, N. (Nora), Gao, W. (Wei), Gläser, S. (Sven), Gu, X. (Xiangjun), Hancock, D.B. (Dana), Heinrich, J. (Joachim), Hofman, A. (Albert), Imboden, M. (Medea), Ingelsson, E. (Erik), James, A. (Alan), Karrasch, S. (Stefan), Koch, B. (Beate), Kritchevsky, S.B. (Stephen), Kumar, A. (Ashish), Lahousse, L. (Lies), Li, G. (Guo), Lind, L. (Lars), Lindgren, C.M. (Cecilia), Liu, Y. (YongMei), Lohman, K. (Kurt), Lumley, T. (Thomas), McArdle, W.L. (Wendy), Meibohm, B. (Bernd), Morris, A.P. (Andrew), Morrison, A.C. (Alanna), Musk, A.W. (Arthur), North, K.E. (Kari), Palmer, C. (Cameron), Probst-Hensch, N.M. (Nicole M.), Psaty, B.M. (Bruce), Rivadeneira Ramirez, F. (Fernando), Rotter, J.I. (Jerome), Schulz, H. (Holger), Smith, L.J. (Lewis), Sood, A. (Akshay), Starr, J.M. (John), Strachan, D.P. (David), Teumer, A. (Alexander), Uitterlinden, A.G. (André), Völzke, H. (Henry), Voorman, J.M. (Jeanine), Wain, L.V. (Louise), Wells, M.T. (Martin), Wilk, J.B. (Jemma), Williams, O.D. (Dale), Heckbert, S.R. (Susan), Stricker, B.H.Ch. (Bruno), London, S.J. (Stephanie), Fornage, M. (Myriam), Tobin, M.D. (Martin), O'Connor, G.T. (George), Hall, I.P. (Ian), Cassano, P.A. (Patricia), Tang, W. (Wenbo), Kowgier, M. (Matthew), Loth, D.W. (Daan), Soler Artigas, M. (Maria), Joubert, B.R. (Bonnie), Hodge, E. (Emily), Gharib, S.A. (Sina), Smith, A.V. (Davey), Ruczinski, I. (Ingo), Gudnason, V. (Vilmundur), Mathias, J. (Jasmine), Harris, T.B. (Tamara), Hansel, C.R.W. (Christian), Launer, L.J. (Lenore), Barnes, K.C. (Kathleen), Hansen, J.G. (Joyanna), Albrecht, E. (Eva), Aldrich, M.C. (Melinda), Allerhand, M.M. (Michael), Barr, R.G. (Graham), Brusselle, G.G. (Guy), Couper, D.J. (David), Curjuric, I. (Ivan), Davies, G. (Gail), Deary, I.J. (Ian), Dupuis, J. (Josée), Fall, M. (Magnus), Foy, M. (Millennia), Franceschini, N. (Nora), Gao, W. (Wei), Gläser, S. (Sven), Gu, X. (Xiangjun), Hancock, D.B. (Dana), Heinrich, J. (Joachim), Hofman, A. (Albert), Imboden, M. (Medea), Ingelsson, E. (Erik), James, A. (Alan), Karrasch, S. (Stefan), Koch, B. (Beate), Kritchevsky, S.B. (Stephen), Kumar, A. (Ashish), Lahousse, L. (Lies), Li, G. (Guo), Lind, L. (Lars), Lindgren, C.M. (Cecilia), Liu, Y. (YongMei), Lohman, K. (Kurt), Lumley, T. (Thomas), McArdle, W.L. (Wendy), Meibohm, B. (Bernd), Morris, A.P. (Andrew), Morrison, A.C. (Alanna), Musk, A.W. (Arthur), North, K.E. (Kari), Palmer, C. (Cameron), Probst-Hensch, N.M. (Nicole M.), Psaty, B.M. (Bruce), Rivadeneira Ramirez, F. (Fernando), Rotter, J.I. (Jerome), Schulz, H. (Holger), Smith, L.J. (Lewis), Sood, A. (Akshay), Starr, J.M. (John), Strachan, D.P. (David), Teumer, A. (Alexander), Uitterlinden, A.G. (André), Völzke, H. (Henry), Voorman, J.M. (Jeanine), Wain, L.V. (Louise), Wells, M.T. (Martin), Wilk, J.B. (Jemma), Williams, O.D. (Dale), Heckbert, S.R. (Susan), Stricker, B.H.Ch. (Bruno), London, S.J. (Stephanie), Fornage, M. (Myriam), Tobin, M.D. (Martin), O'Connor, G.T. (George), Hall, I.P. (Ian), and Cassano, P.A. (Patricia)
Published: 2014
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25. Genetics of coronary artery calcification among African Americans, a meta-analysis

Author: Wojczynski, M.K. (Mary ), Li, M. (Mingyao), Bielak, L.F. (Lawrence F.), Kerr, K.F. (Kathleen), Reiner, A. (Alexander), Wong, N.D. (Nathan), Yanek, L.R. (Lisa), Qu, L. (Liming), White, C.C. (Charles), Lange, L.A. (Leslie), Ferguson, J.F. (Jane), He, J. (Jing), Young, T. (Taylor), Mosley, T.H. (Thomas), Smith, J.A. (Jennifer A), Kral, B.G. (Brian), Guo, X. (Xiuqing), Wong, Q. (Quenna), Ganesh, S.K. (Santhi), Heckbert, S.R. (Susan), Griswold, M.D. (Michael), O'Leary, D.H. (Daniel H.), Budoff, M.J. (Matthew), Carr, J. (Jeffrey), Taylor, H.A. (Herman), Bluemke, D.A. (David), Demissie, S. (Serkalem), Hwang, S.-J. (Shih-Jen), Paltoo, D.N. (Dina), Polak, J.F. (Joseph F.), Psaty, B.M. (Bruce), Becker, D.M. (Diane), Province, M.A. (Mike), Post, W.S. (Wendy S.), O'Donnell, C.J. (Christopher), Wilson, J.G. (James), Harris, T.B. (Tamara), Kavousi, M. (Maryam), Cupples, L.A. (Adrienne), Rotter, J.I. (Jerome), Fornage, M. (Myriam), Becker, L.C. (Lewis), Peyser, P.A. (Patricia A.), Borecki, I.B. (Ingrid), Reilly, M.P. (Muredach), Wojczynski, M.K. (Mary ), Li, M. (Mingyao), Bielak, L.F. (Lawrence F.), Kerr, K.F. (Kathleen), Reiner, A. (Alexander), Wong, N.D. (Nathan), Yanek, L.R. (Lisa), Qu, L. (Liming), White, C.C. (Charles), Lange, L.A. (Leslie), Ferguson, J.F. (Jane), He, J. (Jing), Young, T. (Taylor), Mosley, T.H. (Thomas), Smith, J.A. (Jennifer A), Kral, B.G. (Brian), Guo, X. (Xiuqing), Wong, Q. (Quenna), Ganesh, S.K. (Santhi), Heckbert, S.R. (Susan), Griswold, M.D. (Michael), O'Leary, D.H. (Daniel H.), Budoff, M.J. (Matthew), Carr, J. (Jeffrey), Taylor, H.A. (Herman), Bluemke, D.A. (David), Demissie, S. (Serkalem), Hwang, S.-J. (Shih-Jen), Paltoo, D.N. (Dina), Polak, J.F. (Joseph F.), Psaty, B.M. (Bruce), Becker, D.M. (Diane), Province, M.A. (Mike), Post, W.S. (Wendy S.), O'Donnell, C.J. (Christopher), Wilson, J.G. (James), Harris, T.B. (Tamara), Kavousi, M. (Maryam), Cupples, L.A. (Adrienne), Rotter, J.I. (Jerome), Fornage, M. (Myriam), Becker, L.C. (Lewis), Peyser, P.A. (Patricia A.), Borecki, I.B. (Ingrid), and Reilly, M.P. (Muredach)
Abstract: Background: Coronary heart disease (CHD) is the major cause of death in the United States. Coronary artery calcification (CAC) scores are independent predictors of CHD. African Americans (AA) have higher rates of CHD but are less well-studied in genomic studies. We assembled the largest AA data resource currently available with measured CAC to identify associated genetic variants.Methods: We analyzed log transformed CAC quantity (ln(CAC + 1)), for association with ~2.5 million single nucleotide polymorphisms (SNPs) and performed an inverse-variance weighted meta-analysis on results for 5,823 AA from 8 studies. Heritability was calculated using family studies. The most significant SNPs among AAs were evaluated in European Ancestry (EA) CAC data; conversely, the significance of published SNPs for CAC/CHD in EA was queried within our AA meta-analysis.Results: Heritability of CAC was lower in AA (~30%) than previously reported for EA (~50%). No SNP reached genome wide significance (p < 5E-08). Of 67 SNPs with p < 1E-05 in AA there was no evidence of association in EA CAC data. Four SNPs in regions previously implicated in CAC/CHD (at 9p21 and PHACTR1) in EA reached n
Published: 2013
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26. Incremental value of rare genetic variants for the prediction of multifactorial diseases

Author: Mihaescu, R. (Raluca), Pencina, M. (Michael), Alonso, A. (Alvaro), Lunetta, K.L. (Kathryn), Heckbert, S.R. (Susan), Benjamin, E.J. (Emelia), Janssens, A.C.J.W. (Cécile), Mihaescu, R. (Raluca), Pencina, M. (Michael), Alonso, A. (Alvaro), Lunetta, K.L. (Kathryn), Heckbert, S.R. (Susan), Benjamin, E.J. (Emelia), and Janssens, A.C.J.W. (Cécile)
Abstract: Background: It is often assumed that rare genetic variants will improve available risk prediction scores. We aimed to estimate the added predictive ability of rare variants for risk prediction of common diseases in hypothetical scenarios.Methods: In simulated data, we constructed risk models with an area under the ROC curve (AUC) ranging between 0.50 and 0.95, to which we added a single variant representing the cumulative frequency and effect (odds ratio, OR) of multiple rare variants. The frequency of the rare variant ranged between 0.0001 and 0.01 and the OR between 2 and 10. We assessed the resulting AUC, increment in AUC, integrated discrimination improvement (IDI), net reclassification improvement (NRI(>0.01)) and categorical NRI. The analyses were illustrated by a simulation of atrial fibrillation risk prediction based on a published clinical risk model.Results: We observed minimal improvement in AUC with the addition of rare variants. All measures increased with the frequency and OR of the variant, but maximum increment in AUC remained below 0.05. Increment in AUC and NRI(>0.01) decreased with higher AUC of the baseline model, wh
Published: 2013
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27. Genome-Wide Joint Meta-Analysis of SNP and SNP-by-Smoking Interaction Identifies Novel Loci for Pulmonary Function

Author: Hancock, D.B. (Dana), Artigas, M.S., Gharib, S.A. (Sina), Henry, A. (Amanda), Manichaikul, A. (Ani), Ramasamy, A. (Adaikalavan), Loth, D.W. (Daan), Imboden, M. (Medea), Koch, B. (Beate), McArdle, W.L. (Wendy), Smith, A.V. (Davey), Smolonska, J. (Joanna), Sood, A. (Akshay), Tang, W. (Wenbo), Wilk, J.B. (Jemma), Zhai, G. (Guangju), Zhao, J.H. (Jing Hua), Aschard, H. (Hugues), Burkart, K.M. (Kristin), Curjuric, I. (Ivan), Eijgelsheim, M. (Mark), Elliott, P. (Paul), Gu, X. (Xiangjun), Harris, T.B. (Tamara), Janson, C. (Christer), Homuth, G. (Georg), Hysi, P.G. (Pirro), Liu, J. (Jason), Loehr, L.R. (Laura), Lohman, K. (Kurt), Loos, R.J.F. (Ruth), Manning, A.K. (Alisa), Marciante, K. (Kristin), Obeidat, M. (Ma'en), Postma, D.S. (Dirkje), Aldrich, M.C. (Melinda), Brusselle, G.G. (Guy), Chen, T.H., Eiriksdottir, G. (Gudny), Franceschini, N. (Nora), Heinrich, J. (Joachim), Rotter, J.I. (Jerome), Wijmenga, C. (Cisca), Williams, O.D. (Dale), Hofman, A. (Albert), Laurie, C.C. (Cathy), Lumley, T. (Thomas), Morrison, A.C. (Alanna), Joubert, B.R. (Bonnie), Rivadeneira Ramirez, F. (Fernando), Couper, D.J. (David), Kritchevsky, S.B. (Stephen), Liu, Y. (YongMei), Wjst, M. (Matthias), Wain, L.V. (Louise), Vonk, J.M. (Judith), Uitterlinden, A.G. (André), Rochat, T. (Thierry), Rich, S.S. (Stephen), Psaty, B.M. (Bruce), O'Connor, G.T. (George), North, K.E. (Kari), Mirel, D. (Daniel), Meibohm, B. (Bernd), Launer, L.J. (Lenore), Khaw, K-T. (Kay-Tee), Hartikainen, A.L., Hammond, C.J. (Christopher), Gläser, S. (Sven), Marchini, J. (Jonathan), Kraft, P. (Peter), Wareham, N.J. (Nick), Völzke, H. (Henry), Stricker, B.H.Ch. (Bruno), Spector, T.D. (Timothy), Probst-Hensch, N.M. (Nicole M.), Jarvis, D.L. (Deborah), Jarvelin, M.-R. (Marjo-Riitta), Heckbert, S.R. (Susan), Gudnason, V. (Vilmundur), Boezen, H.M. (Marike), Barr, R.G. (Graham), Cassano, P.A. (Patricia), Strachan, D.P. (David), Fornage, M. (Myriam), Hall, I.P. (Ian), Dupuis, J. (Josée), Tobin, M.D. (Martin), London, S.J. (Stephanie), Bentley, A.R. (Amy), Hancock, D.B. (Dana), Artigas, M.S., Gharib, S.A. (Sina), Henry, A. (Amanda), Manichaikul, A. (Ani), Ramasamy, A. (Adaikalavan), Loth, D.W. (Daan), Imboden, M. (Medea), Koch, B. (Beate), McArdle, W.L. (Wendy), Smith, A.V. (Davey), Smolonska, J. (Joanna), Sood, A. (Akshay), Tang, W. (Wenbo), Wilk, J.B. (Jemma), Zhai, G. (Guangju), Zhao, J.H. (Jing Hua), Aschard, H. (Hugues), Burkart, K.M. (Kristin), Curjuric, I. (Ivan), Eijgelsheim, M. (Mark), Elliott, P. (Paul), Gu, X. (Xiangjun), Harris, T.B. (Tamara), Janson, C. (Christer), Homuth, G. (Georg), Hysi, P.G. (Pirro), Liu, J. (Jason), Loehr, L.R. (Laura), Lohman, K. (Kurt), Loos, R.J.F. (Ruth), Manning, A.K. (Alisa), Marciante, K. (Kristin), Obeidat, M. (Ma'en), Postma, D.S. (Dirkje), Aldrich, M.C. (Melinda), Brusselle, G.G. (Guy), Chen, T.H., Eiriksdottir, G. (Gudny), Franceschini, N. (Nora), Heinrich, J. (Joachim), Rotter, J.I. (Jerome), Wijmenga, C. (Cisca), Williams, O.D. (Dale), Hofman, A. (Albert), Laurie, C.C. (Cathy), Lumley, T. (Thomas), Morrison, A.C. (Alanna), Joubert, B.R. (Bonnie), Rivadeneira Ramirez, F. (Fernando), Couper, D.J. (David), Kritchevsky, S.B. (Stephen), Liu, Y. (YongMei), Wjst, M. (Matthias), Wain, L.V. (Louise), Vonk, J.M. (Judith), Uitterlinden, A.G. (André), Rochat, T. (Thierry), Rich, S.S. (Stephen), Psaty, B.M. (Bruce), O'Connor, G.T. (George), North, K.E. (Kari), Mirel, D. (Daniel), Meibohm, B. (Bernd), Launer, L.J. (Lenore), Khaw, K-T. (Kay-Tee), Hartikainen, A.L., Hammond, C.J. (Christopher), Gläser, S. (Sven), Marchini, J. (Jonathan), Kraft, P. (Peter), Wareham, N.J. (Nick), Völzke, H. (Henry), Stricker, B.H.Ch. (Bruno), Spector, T.D. (Timothy), Probst-Hensch, N.M. (Nicole M.), Jarvis, D.L. (Deborah), Jarvelin, M.-R. (Marjo-Riitta), Heckbert, S.R. (Susan), Gudnason, V. (Vilmundur), Boezen, H.M. (Marike), Barr, R.G. (Graham), Cassano, P.A. (Patricia), Strachan, D.P. (David), Fornage, M. (Myriam), Hall, I.P. (Ian), Dupuis, J. (Josée), Tobin, M.D. (Martin), London, S.J. (Stephanie), and Bentley, A.R. (Amy)
Published: 2012
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28. Genome-wide association studies identify CHRNA5/3 and HTR4 in the development of airflow obstruction

Author: Wilk, J.B. (Jemma), Shrine, N.R.G. (Nick), Loehr, L.R. (Laura), Zhao, J.H. (Jing Hua), Manichaikul, A. (Ani), Lopez, L.M. (Lorna), Smith, A.V. (Davey), Heckbert, S.R. (Susan), Smolonska, J. (Joanna), Tang, W. (Wenbo), Loth, D.W. (Daan), Curjuric, I. (Ivan), Hui, J. (Jennie), Cho, M.H. (Michael), Latourelle, J.C. (Jeanne), Henry, A. (Amanda), Aldrich, M.C. (Melinda), Bakke, A.B. (Arnold B.), Beaty, T.H. (Terri), Bentley, A.R. (Amy), Borecki, I.B. (Ingrid), Brusselle, G.G. (Guy), Burkart, K.M. (Kristin), Chen, T.H., Couper, D.J. (David), Crapo, R.O. (Robert), Davies, G. (Gail), Dupuis, J. (Josée), Franceschini, N. (Nora), Gulsvik, A. (Amund), Hancock, D.B. (Dana), Harris, T.B. (Tamara), Hofman, A. (Albert), Imboden, M. (Medea), James, A.L. (Alan), Khaw, K-T. (Kay-Tee), Lahousse, L. (Lies), Launer, L.J. (Lenore), Litonjua, A.A. (Augusto), Liu, Y. (YongMei), Lohman, K. (Kurt), Lomas, D.J. (David John), Lumley, T. (Thomas), Marciante, K. (Kristin), McArdle, W.L. (Wendy), Meibohm, B. (Bernd), Morrison, A.C. (Alanna), Musk, A.W. (Arthur), Myers, R.H. (Richard), North, K.E. (Kari), Postma, D.S. (Dirkje), Psaty, B.M. (Bruce), Rich, S.S. (Stephen), Rivadeneira Ramirez, F. (Fernando), Rochat, T. (Thierry), Rotter, J.I. (Jerome), Soler Artigas, M. (Maria), Starr, J.M. (John), Uitterlinden, A.G. (André), Wareham, N.J. (Nick), Wijmenga, C. (Cisca), Zanen, P. (Pieter), Province, M.A. (Mike), Silverman, E. (Edwin), Deary, I.J. (Ian), Palmer, C. (Cameron), Cassano, P.A. (Patricia), Gudnason, V. (Vilmundur), Barr, R.G. (Graham), Loos, R.J.F. (Ruth), Strachan, D.P. (David), London, S.J. (Stephanie), Boezen, H.M. (Marike), Probst-Hensch, N. (Nicole), Gharib, S.A. (Sina), Hall, I.P. (Ian), O'Connor, G.T. (George), Tobin, M.D. (Martin), Stricker, B.H.Ch. (Bruno), Wilk, J.B. (Jemma), Shrine, N.R.G. (Nick), Loehr, L.R. (Laura), Zhao, J.H. (Jing Hua), Manichaikul, A. (Ani), Lopez, L.M. (Lorna), Smith, A.V. (Davey), Heckbert, S.R. (Susan), Smolonska, J. (Joanna), Tang, W. (Wenbo), Loth, D.W. (Daan), Curjuric, I. (Ivan), Hui, J. (Jennie), Cho, M.H. (Michael), Latourelle, J.C. (Jeanne), Henry, A. (Amanda), Aldrich, M.C. (Melinda), Bakke, A.B. (Arnold B.), Beaty, T.H. (Terri), Bentley, A.R. (Amy), Borecki, I.B. (Ingrid), Brusselle, G.G. (Guy), Burkart, K.M. (Kristin), Chen, T.H., Couper, D.J. (David), Crapo, R.O. (Robert), Davies, G. (Gail), Dupuis, J. (Josée), Franceschini, N. (Nora), Gulsvik, A. (Amund), Hancock, D.B. (Dana), Harris, T.B. (Tamara), Hofman, A. (Albert), Imboden, M. (Medea), James, A.L. (Alan), Khaw, K-T. (Kay-Tee), Lahousse, L. (Lies), Launer, L.J. (Lenore), Litonjua, A.A. (Augusto), Liu, Y. (YongMei), Lohman, K. (Kurt), Lomas, D.J. (David John), Lumley, T. (Thomas), Marciante, K. (Kristin), McArdle, W.L. (Wendy), Meibohm, B. (Bernd), Morrison, A.C. (Alanna), Musk, A.W. (Arthur), Myers, R.H. (Richard), North, K.E. (Kari), Postma, D.S. (Dirkje), Psaty, B.M. (Bruce), Rich, S.S. (Stephen), Rivadeneira Ramirez, F. (Fernando), Rochat, T. (Thierry), Rotter, J.I. (Jerome), Soler Artigas, M. (Maria), Starr, J.M. (John), Uitterlinden, A.G. (André), Wareham, N.J. (Nick), Wijmenga, C. (Cisca), Zanen, P. (Pieter), Province, M.A. (Mike), Silverman, E. (Edwin), Deary, I.J. (Ian), Palmer, C. (Cameron), Cassano, P.A. (Patricia), Gudnason, V. (Vilmundur), Barr, R.G. (Graham), Loos, R.J.F. (Ruth), Strachan, D.P. (David), London, S.J. (Stephanie), Boezen, H.M. (Marike), Probst-Hensch, N. (Nicole), Gharib, S.A. (Sina), Hall, I.P. (Ian), O'Connor, G.T. (George), Tobin, M.D. (Martin), and Stricker, B.H.Ch. (Bruno)
Abstract: Rationale: Genome-wide association studies (GWAS) have identified loci influencing lung function, but fewer genes influencing chronic obstructive pulmonary disease (COPD) are known. Objectives: Perform meta-analyses of GWAS for airflow obstruction, a key pathophysiologic characteristic ofCOPD assessedby spirometry, in population-based cohorts examining all participants, ever smokers, never smokers, asthma-free participants, and more severe cases. Methods: Fif
Published: 2012
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29. Genome-wide association studies of cerebral white matter lesion burden

Author: 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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30. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk

Author: 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
Published: 2011
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31. Genetic variation associated with plasma vonWillebrand factor levels and the risk of incident venous thrombosis

Author: Smith, N.L. (Nicholas), Rice, K.M. (Kenneth), Bovill, E.G. (Edwin G.), Cushman, M. (Mary Ann), Bis, J.C. (Joshua), McKnight, B. (Barbara), Lumley, T. (Thomas), Glazer, N.L. (Nicole), Hylckama Vlieg, A. (Astrid) van, Tang, W. (Weihong), Dehghan, A. (Abbas), Strachan, D.P. (David), O'Donnell, C.J. (Christopher), Rotter, J.I. (Jerome), Heckbert, S.R. (Susan), Psaty, B.M. (Bruce), Rosendaal, F.R. (Frits), Smith, N.L. (Nicholas), Rice, K.M. (Kenneth), Bovill, E.G. (Edwin G.), Cushman, M. (Mary Ann), Bis, J.C. (Joshua), McKnight, B. (Barbara), Lumley, T. (Thomas), Glazer, N.L. (Nicole), Hylckama Vlieg, A. (Astrid) van, Tang, W. (Weihong), Dehghan, A. (Abbas), Strachan, D.P. (David), O'Donnell, C.J. (Christopher), Rotter, J.I. (Jerome), Heckbert, S.R. (Susan), Psaty, B.M. (Bruce), and Rosendaal, F.R. (Frits)
Abstract: In a recent genome-wide association study, variants in 8 genes were associated with VWF level, a risk factor for venous thrombosis (VT). In an independent, population-based, case-control study of incident VT, we tested hypotheses that variants in these genes would be associated with risk. Cases were 656 women who experienced an incident VT, and controls comprised 710 women without a history of VT. DNAwas obtained from whole blood. Logistic regression was used to test associations between incident VT and single nucleotide polymorphisms (SNPs) in 7 genes not previously shown to be associated with VT. Associations with P < .05 were candidates for replication in an independent case-control study of VT in both sexes. Two of the 7 SNPs tested yielded P < .05: rs1039084 (P = .005) in STXBP5, a novel candidate gene for VT, and rs1063856 (P = .04) in VWF, a gene whose protein level is associated with VT risk. Association results for the remaining 5 variants in SCARA5, STAB2, STX2, TC2N, and CLEC4M were not significant. Both STXBP5 and VWF findings were replicated successfully. Variation in genes associated with VWF levels in the genomewide association study was found to be independently associated with incident VT.
Published: 2011
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32. RANTES/CCL5 and risk for coronary events: Results from the MONICA/KORA Augsburg case-cohort, Athero-express and CARDIoGRAM studies

Author: Kathiresan, S. (Sekar), Reilly, M.P. (Muredach), Samani, N.J. (Nilesh), Schunkert, H. (Heribert), Erdmann, J. (Jeanette), Moll, F.L. (Frans), Boerwinkle, E.A. (Eric), Hall, A. (Anne), Hengstenberg, C. (Christian), König, I.R. (Inke), Laaksonen, R. (Reijo), McPherson, R. (Ruth), Thompson, J.R. (John), Thorsteinsdottir, U. (Unnur), Ziegler, A. (Andreas), Koenig, W. (Wolfgang), Chen, L. (Li), Cupples, L.A. (Adrienne), Halperin, E. (Eran), Musunuru, K. (Kiran), Preuss, M. (Michael), Schillert, A. (Arne), Thorleifsson, G. (Gudmar), Voight, B.F. (Benjamin), Wells, G.A. (George), Deloukas, P. (Panagiotis), Holm, H. (Hilma), Roberts, R. (Robert), Stewart, A.F.R. (Alexandre), Fortmann, S.P. (Stephen), Go, A.T.J.I. (Attie), Hlatky, M.A. (Mark), Iribarren, C. (Carlos), Knowles, J.W. (Joshua), Myers, R.H. (Richard), Quertermous, T. (Thomas), Sidney, S. (Steven), Risch, N., Tang, H. (Hui), Blankenberg, S. (Stefan), Zeller, T. (Tanja), Wild, P.S. (Philipp), Schnabel, R.B. (Renate), Sinning, C. (Christoph), Lackner, K.J. (Karl), Tiret, L. (Laurence), Nicaud, V., Cambien, F. (François), Bickel, H. (Horst), Rupprecht, H.J., Perret, C. (Claire), Proust, C. (Carole), Munzel, T. (Thomas), Barbalic, M. (maja), Bis, J.C. (Joshua), Chen, I.Y.-D. (Ida Yii-Der), Dehghan, A. (Abbas), Demissie-Banjaw, S. (Serkalem), Folsom, A.R. (Aaron), Glazer, N.L. (Nicole), Gudnason, V. (Vilmundur), Harris, T.B. (Tamara), Heckbert, S.R. (Susan), Levy, D. (Daniel), Lumley, T. (Thomas), Marciante, K. (Kristin), Morrison, A.C. (Alanna), O'Donnell, C.J. (Christopher), Psaty, B.M. (Bruce), Rice, K. (Kenneth), Rotter, J.I. (Jerome), Siscovick, D.S. (David), Smith, N.L. (Nicholas), Smith, A.V. (Davey), Taylor, K.D. (Kent), Duijn, C.M. (Cornelia) van, Volcik, K.A. (Kelly), Whitteman, J. (Jaqueline), Ramachandran, V.S. (Vasan), Hofman, A. (Albert), Uitterlinden, A.G. (André), Gretarsdottir, S. (Solveig), Gulcher, J.R. (Jeffrey), Kong, A. (Augustine), Zwart, J-A. (John-Anker), Thorgeirsson, G. (Gudmundur), Andersen, K.K. (Karl), Fischer, M. (Marcus), Großhennig, A. (Anika), Lieb, W. (Wolfgang), Linsel-Nitschke, P. (Patrick), Stark, K. (Klaus), Schreiber, S. (Stefan), Wichmann, H.E. (Heinz Erich), Aherrahrou, Z. (Zouhair), Bruse, P. (Petra), Doering, A. (Angela), Illig, T. (Thomas), Klopp, N. (Norman), Loley, C. (Christina), Medack, A. (Anja), Meisinger, C. (Christa), Meitinger, T. (Thomas), Nahrstedt, J. (Janja), Peters, A. (Annette), Wagner, A.K. (Arnika), Willenborg, C. (Christina), Böhm, B., Dobnig, H. (Harald), Grammer, T.B. (Tanja), Hoffmann, M.M. (Michael), Kleber, M. (Martina), März, W. (Winfried), Meinitzer, A. (Andreas), Winkelmann, B., Pilz, D.T. (Daniela), Renner, W. (Wilfried), Scharnagl, H. (Hubert), Stojakovic, T. (Tatjana), Tomaschitz, A. (Andreas), Winkler, K. (Karl), Guiducci, C. (Candace), Burtt, N.P. (Noël), Gabriel, S.B. (Stacey), Elosua, R. (Roberto), Peltonen, L. (Leena Johanna), Salomaa, V. (Veikko), Schwartz, S.M. (Stephen), Melander, O. (Olle), Altshuler, D. (David), Dandona, S. (Sonny), Jarinova, O. (Olga), Qu, L. (Liming), Wilensky, A. (Asaf), Matthai, W. (William), Hakonarson, H. (Hakon), Devaney, J. (Joseph), Burnett, M.S., Pichard, A.D., Kent, K.M. (Kenneth), Satler, L.F., Lindsay, J.M. (Joseph), Waksman, R. (Ron), Knouff, C.W. (Christopher), Waterworth, D. (Dawn), Walker, M.C. (Max), Mooser, V. (Vincent), Epstein, S.E. (Stephen), Rader, D.J. (Daniel), Braund, P.S. (Peter), Nelson, C.P. (Christopher P.), Li, M. (Mingyao), Wright, B.J. (Benjamin), Balmforth, A.J. (Anthony), Ball, S.G. (Stephen), Kathiresan, S. (Sekar), Reilly, M.P. (Muredach), Samani, N.J. (Nilesh), Schunkert, H. (Heribert), Erdmann, J. (Jeanette), Moll, F.L. (Frans), Boerwinkle, E.A. (Eric), Hall, A. (Anne), Hengstenberg, C. (Christian), König, I.R. (Inke), Laaksonen, R. (Reijo), McPherson, R. (Ruth), Thompson, J.R. (John), Thorsteinsdottir, U. (Unnur), Ziegler, A. (Andreas), Koenig, W. (Wolfgang), Chen, L. (Li), Cupples, L.A. (Adrienne), Halperin, E. (Eran), Musunuru, K. (Kiran), Preuss, M. (Michael), Schillert, A. (Arne), Thorleifsson, G. (Gudmar), Voight, B.F. (Benjamin), Wells, G.A. (George), Deloukas, P. (Panagiotis), Holm, H. (Hilma), Roberts, R. (Robert), Stewart, A.F.R. (Alexandre), Fortmann, S.P. (Stephen), Go, A.T.J.I. (Attie), Hlatky, M.A. (Mark), Iribarren, C. (Carlos), Knowles, J.W. (Joshua), Myers, R.H. (Richard), Quertermous, T. (Thomas), Sidney, S. (Steven), Risch, N., Tang, H. (Hui), Blankenberg, S. (Stefan), Zeller, T. (Tanja), Wild, P.S. (Philipp), Schnabel, R.B. (Renate), Sinning, C. (Christoph), Lackner, K.J. (Karl), Tiret, L. (Laurence), Nicaud, V., Cambien, F. (François), Bickel, H. (Horst), Rupprecht, H.J., Perret, C. (Claire), Proust, C. (Carole), Munzel, T. (Thomas), Barbalic, M. (maja), Bis, J.C. (Joshua), Chen, I.Y.-D. (Ida Yii-Der), Dehghan, A. (Abbas), Demissie-Banjaw, S. (Serkalem), Folsom, A.R. (Aaron), Glazer, N.L. (Nicole), Gudnason, V. (Vilmundur), Harris, T.B. (Tamara), Heckbert, S.R. (Susan), Levy, D. (Daniel), Lumley, T. (Thomas), Marciante, K. (Kristin), Morrison, A.C. (Alanna), O'Donnell, C.J. (Christopher), Psaty, B.M. (Bruce), Rice, K. (Kenneth), Rotter, J.I. (Jerome), Siscovick, D.S. (David), Smith, N.L. (Nicholas), Smith, A.V. (Davey), Taylor, K.D. (Kent), Duijn, C.M. (Cornelia) van, Volcik, K.A. (Kelly), Whitteman, J. (Jaqueline), Ramachandran, V.S. (Vasan), Hofman, A. (Albert), Uitterlinden, A.G. (André), Gretarsdottir, S. (Solveig), Gulcher, J.R. (Jeffrey), Kong, A. (Augustine), Zwart, J-A. (John-Anker), Thorgeirsson, G. (Gudmundur), Andersen, K.K. (Karl), Fischer, M. (Marcus), Großhennig, A. (Anika), Lieb, W. (Wolfgang), Linsel-Nitschke, P. (Patrick), Stark, K. (Klaus), Schreiber, S. (Stefan), Wichmann, H.E. (Heinz Erich), Aherrahrou, Z. (Zouhair), Bruse, P. (Petra), Doering, A. (Angela), Illig, T. (Thomas), Klopp, N. (Norman), Loley, C. (Christina), Medack, A. (Anja), Meisinger, C. (Christa), Meitinger, T. (Thomas), Nahrstedt, J. (Janja), Peters, A. (Annette), Wagner, A.K. (Arnika), Willenborg, C. (Christina), Böhm, B., Dobnig, H. (Harald), Grammer, T.B. (Tanja), Hoffmann, M.M. (Michael), Kleber, M. (Martina), März, W. (Winfried), Meinitzer, A. (Andreas), Winkelmann, B., Pilz, D.T. (Daniela), Renner, W. (Wilfried), Scharnagl, H. (Hubert), Stojakovic, T. (Tatjana), Tomaschitz, A. (Andreas), Winkler, K. (Karl), Guiducci, C. (Candace), Burtt, N.P. (Noël), Gabriel, S.B. (Stacey), Elosua, R. (Roberto), Peltonen, L. (Leena Johanna), Salomaa, V. (Veikko), Schwartz, S.M. (Stephen), Melander, O. (Olle), Altshuler, D. (David), Dandona, S. (Sonny), Jarinova, O. (Olga), Qu, L. (Liming), Wilensky, A. (Asaf), Matthai, W. (William), Hakonarson, H. (Hakon), Devaney, J. (Joseph), Burnett, M.S., Pichard, A.D., Kent, K.M. (Kenneth), Satler, L.F., Lindsay, J.M. (Joseph), Waksman, R. (Ron), Knouff, C.W. (Christopher), Waterworth, D. (Dawn), Walker, M.C. (Max), Mooser, V. (Vincent), Epstein, S.E. (Stephen), Rader, D.J. (Daniel), Braund, P.S. (Peter), Nelson, C.P. (Christopher P.), Li, M. (Mingyao), Wright, B.J. (Benjamin), Balmforth, A.J. (Anthony), and Ball, S.G. (Stephen)
Abstract: Background: The chemokine RANTES (regulated on activation, normal T-cell expressed and secreted)/CCL5 is involved in the pathogenesis of cardiovascular disease in mice, whereas less is known in humans. We hypothesised that its relevance for atherosclerosis should be reflected by associations between CCL5 gene variants, RANTES serum concentrations and protein levels in atherosclerotic plaques and risk for coronary events. Methods and Findings: We conducted a case-cohort study within the population-based MONICA/KORA Augsburg studies. Baseline RANTES serum levels were measured in 363 individuals with incident coronary events and 1,908 non-cases (mean follow-up: 10.2±4
Published: 2011
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33. Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque

Author: Bis, J.C. (Joshua), Kavousi, M. (Maryam), Franceschini, N. (Nora), Isaacs, A.J. (Aaron), Abecasis, G.R. (Gonçalo), Schminke, U. (Ulf), Post, W.S. (Wendy S.), Smith, A.V. (Albert Vernon), Cupples, L.A. (Adrienne), Markus, H.S. (Hugh S.), Schmidt, R. (Reinhold), Huffman, J.E. (Jennifer), Lehtimäki, T. (Terho), Baumert, J. (Jens), Münzel, T. (Thomas), Heckbert, S.R. (Susan), Dehghan, A. (Abbas), North, K.E. (Kari), Oostra, B.A. (Ben), Bevan, S. (Steve), Stoegerer, E.M. (Eva Maria), Hayward, C. (Caroline), Raitakari, O. (Olli), Meisinger, C. (Christa), Schillert, A. (Arne), Sanna, S. (Serena), Völzke, H. (Henry), Cheng, Y.C. (Yu Ching), Thorsson, B. (Bolli), Fox, C.S. (Caroline), Rice, K. (Kenneth), Rivadeneira Ramirez, F. (Fernando), Nambi, V. (Vijay), Halperin, E. (Eran), Petrovic, K. (Katja), Peltonen, L. (Leena Johanna), Wichmann, H.E. (Heinz Erich), Schnabel, R.B. (Renate), Dörr, M. (Marcus), Parsa, A. (Afshin), Aspelund, T. (Thor), Demissie, S. (Serkalem), Kathiresan, S. (Sekar), Reilly, M.P. (Muredach), Taylor, K.D. (Kent), Uitterlinden, A.G. (André), Couper, D.J. (David), Sitzer, M. (Matthias), Kähönen, M. (Mika), Illig, T. (Thomas), Wild, P.S. (Philipp), Orrù, M. (Marco), Lüdemann, J. (Jan), Shuldiner, A.R. (Alan), Eiriksdottir, G. (Gudny), White, C.C. (Charles), Rotter, J.I. (Jerome), Hofman, A. (Albert), Seissler, J. (Jochen), Zeller, T. (Tanja), Usala, G., Ernst, F.D.J. (Florian), Launer, L.J. (Lenore), D'Agostino, R.B. (Ralph), O'Leary, D.H. (Daniel H.), Ballantyne, C. (Christie), Thiery, J.P. (Joachim), Ziegler, A. (Andreas), Lakatta, E. (Edward), Chilukoti, R.K. (Ravi Kumar), Harris, T.B. (Tamara), Wolf, P.A. (Philip), Psaty, B.M. (Bruce), Polak, J.F. (Joseph F.), Rathmann, W. (Wolfgang), Uda, M. (Manuela), Boerwinkle, E.A. (Eric), Klopp, N. (Norman), Wilson, J.F. (James), Viikari, J. (Jorma), Koenig, W. (Wolfgang), Blankenberg, S. (Stefan), Newman, A.B. (Anne), Witteman, J.C.M. (Jacqueline), Li, X. (Xia), Heiss, G. (Gerardo), Duijn, C.M. (Cornelia) van, Scuteri, A. (Angelo), Homuth, G. (Georg), Mitchell, B.D. (Braxton), Gudnason, V. (Vilmundur), O'Donnell, C.J. (Christopher), Bis, J.C. (Joshua), Kavousi, M. (Maryam), Franceschini, N. (Nora), Isaacs, A.J. (Aaron), Abecasis, G.R. (Gonçalo), Schminke, U. (Ulf), Post, W.S. (Wendy S.), Smith, A.V. (Albert Vernon), Cupples, L.A. (Adrienne), Markus, H.S. (Hugh S.), Schmidt, R. (Reinhold), Huffman, J.E. (Jennifer), Lehtimäki, T. (Terho), Baumert, J. (Jens), Münzel, T. (Thomas), Heckbert, S.R. (Susan), Dehghan, A. (Abbas), North, K.E. (Kari), Oostra, B.A. (Ben), Bevan, S. (Steve), Stoegerer, E.M. (Eva Maria), Hayward, C. (Caroline), Raitakari, O. (Olli), Meisinger, C. (Christa), Schillert, A. (Arne), Sanna, S. (Serena), Völzke, H. (Henry), Cheng, Y.C. (Yu Ching), Thorsson, B. (Bolli), Fox, C.S. (Caroline), Rice, K. (Kenneth), Rivadeneira Ramirez, F. (Fernando), Nambi, V. (Vijay), Halperin, E. (Eran), Petrovic, K. (Katja), Peltonen, L. (Leena Johanna), Wichmann, H.E. (Heinz Erich), Schnabel, R.B. (Renate), Dörr, M. (Marcus), Parsa, A. (Afshin), Aspelund, T. (Thor), Demissie, S. (Serkalem), Kathiresan, S. (Sekar), Reilly, M.P. (Muredach), Taylor, K.D. (Kent), Uitterlinden, A.G. (André), Couper, D.J. (David), Sitzer, M. (Matthias), Kähönen, M. (Mika), Illig, T. (Thomas), Wild, P.S. (Philipp), Orrù, M. (Marco), Lüdemann, J. (Jan), Shuldiner, A.R. (Alan), Eiriksdottir, G. (Gudny), White, C.C. (Charles), Rotter, J.I. (Jerome), Hofman, A. (Albert), Seissler, J. (Jochen), Zeller, T. (Tanja), Usala, G., Ernst, F.D.J. (Florian), Launer, L.J. (Lenore), D'Agostino, R.B. (Ralph), O'Leary, D.H. (Daniel H.), Ballantyne, C. (Christie), Thiery, J.P. (Joachim), Ziegler, A. (Andreas), Lakatta, E. (Edward), Chilukoti, R.K. (Ravi Kumar), Harris, T.B. (Tamara), Wolf, P.A. (Philip), Psaty, B.M. (Bruce), Polak, J.F. (Joseph F.), Rathmann, W. (Wolfgang), Uda, M. (Manuela), Boerwinkle, E.A. (Eric), Klopp, N. (Norman), Wilson, J.F. (James), Viikari, J. (Jorma), Koenig, W. (Wolfgang), Blankenberg, S. (Stefan), Newman, A.B. (Anne), Witteman, J.C.M. (Jacqueline), Li, X. (Xia), Heiss, G. (Gerardo), Duijn, C.M. (Cornelia) van, Scuteri, A. (Angelo), Homuth, G. (Georg), Mitchell, B.D. (Braxton), Gudnason, V. (Vilmundur), and O'Donnell, C.J. (Christopher)
Abstract: Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 × 10 -8). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events.
Published: 2011
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34. Independent susceptibility markers for atrial fibrillation on chromosome 4q25

Author: Lubitz, S.A. (Steven), Sinner, M.F. (Moritz), Lunetta, K.L. (Kathryn), Makino, S. (Seiko), Pfeufer, A. (Arne), Rahman, R. (Rosanna), Veltman, C.E. (Caroline), Barnard, J. (John), Bis, J.C. (Joshua), Danik, S.P. (Stephan), Sonni, A. (Akshata), Shea, M.A. (Marisa), Del Monte, F. (Federica), Perz, S. (Siegfried), Muller, M. (Majon), Peters, A. (Annette), Greenberg, S.M. (Steven), Furie, K.L. (Karen), Noord, C. (Charlotte) van, Boerwinkle, E.A. (Eric), Stricker, B.H.Ch. (Bruno), Witteman, J.C.M. (Jacqueline), Smith, J.D. (Jonathan), Chung, M.K. (Mina), Heckbert, S.R. (Susan), Benjamin, E.J. (Emelia), Rosand, J. (Jonathan), Arking, D.E. (Dan), Alonso, A. (Alvaro), Kääb, S. (Stefan), Ellinor, P.T. (Patrick), Lubitz, S.A. (Steven), Sinner, M.F. (Moritz), Lunetta, K.L. (Kathryn), Makino, S. (Seiko), Pfeufer, A. (Arne), Rahman, R. (Rosanna), Veltman, C.E. (Caroline), Barnard, J. (John), Bis, J.C. (Joshua), Danik, S.P. (Stephan), Sonni, A. (Akshata), Shea, M.A. (Marisa), Del Monte, F. (Federica), Perz, S. (Siegfried), Muller, M. (Majon), Peters, A. (Annette), Greenberg, S.M. (Steven), Furie, K.L. (Karen), Noord, C. (Charlotte) van, Boerwinkle, E.A. (Eric), Stricker, B.H.Ch. (Bruno), Witteman, J.C.M. (Jacqueline), Smith, J.D. (Jonathan), Chung, M.K. (Mina), Heckbert, S.R. (Susan), Benjamin, E.J. (Emelia), Rosand, J. (Jonathan), Arking, D.E. (Dan), Alonso, A. (Alvaro), Kääb, S. (Stefan), and Ellinor, P.T. (Patrick)
Abstract: Background-: Genetic variants on chromosome 4q25 are associated with atrial fibrillation (AF). We sought to determine whether there is more than 1 susceptibility signal at this locus. Methods and results-: Thirty-four haplotype-tagging single-nucleotide polymorphisms (SNPs) at the 4q25 locus were genotyped in 790 case and 1177 control subjects from Massachusetts General Hospital and tested for association with AF. We replicated SNPs associated with AF after adjustment for the most significantly associated SNP in 5066 case and 30 661 referent subjects from the German Competence Network for Atrial Fibrillation, Atherosclerosis Risk In Communities Study, Cleveland Clinic Lone AF Study, Cardiovascular Health Study, and Rotterdam Study. All subjects were of European ancestry. A multimarker risk score composed of SNPs that tagged distinct AF susceptibility signals was constructed and tested for association with AF, and all results were subjected to meta-analysis. The previously reported SNP, rs2200733, was most significantly associated with AF (minor allele odds ratio 1.80, 95% confidence interval 1.50 to 2.15, P=1.2×10) in the discovery sample. Adjustment for rs2200733 genotype revealed 2 additional susceptibility signals marked by rs17570669 and rs3853445. A graded risk of AF was observed with an increasing number of AF risk alleles at SNPs that tagged these 3 susceptibility signals. Conclusions-: We identified 2 novel AF susceptibility signals on chromosome 4q25. Consideration of multiple susceptibility signals at chromosome 4q25 identifies individuals with an increased risk of AF and may localize regulatory elements at the locus with biological relevance in the pathogenesis of AF.
Published: 2010
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35. Four novel loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation In vivo

Author: Ikram, M.K. (Kamran), Xueling, S. (Sim), Jensen, R.A. (Richard), Cotch, M.F. (Mary Frances), Hewit, A.W. (Alex), Ikram, M.A. (Arfan), Wang, J.J. (Jie Jin), Klein, B.E.K. (Barbara), Breteler, M.M.B. (Monique), Cheung, N. (Ning), Liew, G. (Gerald), Mitchell, P. (Paul), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Hofman, A. (Albert), Jong, P.T.V.M. (Paulus) de, Duijn, C.M. (Cornelia) van, Kao, L. (Linda), Cheng, C-Y. (Ching-Yu), Smith, A.V. (Albert Vernon), Glazer, N.L. (Nicole), Lumley, T. (Thomas), McKnight, B. (Barbara), Psaty, B.M. (Bruce), Jonasson, F. (Fridbert), Eiriksdottir, G. (Gudny), Aspelund, T. (Thor), Harris, T.B. (Tamara), Launer, L.J. (Lenore), Taylor, K.D. (Kent), Li, X. (Xiaohui), Sivakumaran, T.A. (Theru), Mackey, D.A. (David), MacGregor, S. (Stuart), Martin, N.G. (Nicholas), Young, T.L. (Terry), Bis, J.C. (Joshua), Wiggins, K.L. (Kerri), Heckbert, S.R. (Susan), Hammond, C.J. (Christopher), Andrew, T. (Toby), Fahy, S. (Samantha), Attia, J. (John), Holliday, E.G. (Elizabeth), Scott, R.J. (Rodney), Islam, F.M.A. (Amirul), Rotter, J.I. (Jerome), McAuley, A.K. (Annie), Boerwinkle, E.A. (Eric), Tai, E.S. (Shyong), Gudnason, V. (Vilmundur), Siscovick, D.S. (David), Vingerling, J.R. (Hans), Wong, T.Y. (Tien Yin), Ikram, M.K. (Kamran), Xueling, S. (Sim), Jensen, R.A. (Richard), Cotch, M.F. (Mary Frances), Hewit, A.W. (Alex), Ikram, M.A. (Arfan), Wang, J.J. (Jie Jin), Klein, B.E.K. (Barbara), Breteler, M.M.B. (Monique), Cheung, N. (Ning), Liew, G. (Gerald), Mitchell, P. (Paul), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Hofman, A. (Albert), Jong, P.T.V.M. (Paulus) de, Duijn, C.M. (Cornelia) van, Kao, L. (Linda), Cheng, C-Y. (Ching-Yu), Smith, A.V. (Albert Vernon), Glazer, N.L. (Nicole), Lumley, T. (Thomas), McKnight, B. (Barbara), Psaty, B.M. (Bruce), Jonasson, F. (Fridbert), Eiriksdottir, G. (Gudny), Aspelund, T. (Thor), Harris, T.B. (Tamara), Launer, L.J. (Lenore), Taylor, K.D. (Kent), Li, X. (Xiaohui), Sivakumaran, T.A. (Theru), Mackey, D.A. (David), MacGregor, S. (Stuart), Martin, N.G. (Nicholas), Young, T.L. (Terry), Bis, J.C. (Joshua), Wiggins, K.L. (Kerri), Heckbert, S.R. (Susan), Hammond, C.J. (Christopher), Andrew, T. (Toby), Fahy, S. (Samantha), Attia, J. (John), Holliday, E.G. (Elizabeth), Scott, R.J. (Rodney), Islam, F.M.A. (Amirul), Rotter, J.I. (Jerome), McAuley, A.K. (Annie), Boerwinkle, E.A. (Eric), Tai, E.S. (Shyong), Gudnason, V. (Vilmundur), Siscovick, D.S. (David), Vingerling, J.R. (Hans), and Wong, T.Y. (Tien Yin)
Abstract: There is increasing evidence that the microcirculation plays an important role in the pathogenesis of cardiovascular diseases. Changes in retinal vascular caliber reflect early microvascular disease and predict incident cardiovascular events. We performed a genome-wide association study to identify genetic variants associated with retinal vascular caliber. We analyzed data from four population-based discovery cohorts with 15,358 unrelated Caucasian individuals, who are members of the Cohort for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and replicated findings in four independent Caucasian cohorts (n = 6,652). All participants had retinal photography and retinal arteriolar and venular caliber measured from computer software. In the discovery cohorts, 179 single nucleotide polymorphisms (SNP) spread across five loci were significantly associated (p<5.0×10-8) with retinal venular caliber, but none showed association with arteriolar caliber. Collectively, these five loci explain 1.0%-3.2% of the variation in retinal venular caliber. Four out of these five loci were confirmed in independent replication samples. In the combined analyses, the top SNPs at each locus were: rs2287921 (19q13; p = 1.61×10-25, within the RASIP1 locus), rs225717 (6q24; p = 1.25×10-16, adjacent to the VTA1 and NMBR loci), rs10774625 (12q24; p = 2.15×10-13, in the region of ATXN2,SH2B3 and PTPN11 loci), and rs17421627 (5q14; p = 7.32×10-16, adjacent to the MEF2C locus). In two independent samples, locus 12q24 was also associated with coronary heart disease and hypertension. Our population-based genome-wide association study demonstrates four novel loci associated with retinal venular caliber, an endophenotype of the microcirculation associated with clinical cardiovascular disease. These data provide further insights into the contribution and biological mechanisms of microcirculatory changes that underlie cardiovascular disease.
Published: 2010
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36. Genome-wide association analysis identifies multiple loci related to resting heart rate

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

Author: 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.
Published: 2010
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38. Common variants in KCNN3 are associated with lone atrial fibrillation

Author: Ellinor, P.T. (Patrick), Lunetta, K.L. (Kathryn), Glazer, N.L. (Nicole), Pfeufer, A. (Arne), Alonso, A. (Alvaro), Chung, M.K. (Mina), Sinner, M.F. (Moritz), Bakker, P.I.W. (Paul) de, Mueller, M. (Martina), Lubitz, S.A. (Steven), Fox, E.R. (Ervin), Darbar, D. (Dawood), Smith, N.L. (Nicholas), Schnabel, R. (Renate), Soliman, E.Z. (Elsayed), Rice, K. (Kenneth), Wagoner, D.R. (David) van, Beckmann, B.M. (Britt), Noord, C. (Charlotte) van, Wang, T.J. (Thomas), Ehret, G.B. (Georg), Rotter, J.I. (Jerome), Hazen, S.L. (Stanley), Steinbeck, G. (Gerhard), Launer, L.J. (Lenore), Harris, T.B. (Tamara), Makino, S. (Seiko), Nelis, M. (Mari), Milan, D.J. (David), Perz, S. (Siegfried), Esko, T. (Tõnu), Köttgen, A. (Anna), Moebus, S. (Susanne), Newton-Cheh, C. (Christopher), Li, M. (Man), Möhlenkamp, S. (Stefan), Kao, W.-H.L. (Linda), Vasan, R.S. (Ramachandran Srini), Nöthen, M.M. (Markus), MacRae, C.A. (Calum), Stricker, B.H.Ch. (Bruno), Hofman, A. (Albert), Uitterlinden, A.G. (André), Levy, D. (Daniel), Boerwinkle, E.A. (Eric), Metspalu, A. (Andres), Topol, E.J. (Eric), Chakravarti, A. (Aravinda), Gudnason, V. (Vilmundur), Psaty, B.M. (Bruce), Roden, D.M. (Dan), Meitinger, T. (Thomas), Wichmann, H.E. (Erich), Witteman, J.C.M. (Jacqueline), Barnard, J. (John), Arking, D.E. (Dan), Benjamin, E.J. (Emelia), Heckbert, S.R. (Susan), Kääb, S. (Stefan), Ellinor, P.T. (Patrick), Lunetta, K.L. (Kathryn), Glazer, N.L. (Nicole), Pfeufer, A. (Arne), Alonso, A. (Alvaro), Chung, M.K. (Mina), Sinner, M.F. (Moritz), Bakker, P.I.W. (Paul) de, Mueller, M. (Martina), Lubitz, S.A. (Steven), Fox, E.R. (Ervin), Darbar, D. (Dawood), Smith, N.L. (Nicholas), Schnabel, R. (Renate), Soliman, E.Z. (Elsayed), Rice, K. (Kenneth), Wagoner, D.R. (David) van, Beckmann, B.M. (Britt), Noord, C. (Charlotte) van, Wang, T.J. (Thomas), Ehret, G.B. (Georg), Rotter, J.I. (Jerome), Hazen, S.L. (Stanley), Steinbeck, G. (Gerhard), Launer, L.J. (Lenore), Harris, T.B. (Tamara), Makino, S. (Seiko), Nelis, M. (Mari), Milan, D.J. (David), Perz, S. (Siegfried), Esko, T. (Tõnu), Köttgen, A. (Anna), Moebus, S. (Susanne), Newton-Cheh, C. (Christopher), Li, M. (Man), Möhlenkamp, S. (Stefan), Kao, W.-H.L. (Linda), Vasan, R.S. (Ramachandran Srini), Nöthen, M.M. (Markus), MacRae, C.A. (Calum), Stricker, B.H.Ch. (Bruno), Hofman, A. (Albert), Uitterlinden, A.G. (André), Levy, D. (Daniel), Boerwinkle, E.A. (Eric), Metspalu, A. (Andres), Topol, E.J. (Eric), Chakravarti, A. (Aravinda), Gudnason, V. (Vilmundur), Psaty, B.M. (Bruce), Roden, D.M. (Dan), Meitinger, T. (Thomas), Wichmann, H.E. (Erich), Witteman, J.C.M. (Jacqueline), Barnard, J. (John), Arking, D.E. (Dan), Benjamin, E.J. (Emelia), Heckbert, S.R. (Susan), and Kääb, S. (Stefan)
Abstract: Atrial fibrillation (AF) is the most common sustained arrhythmia. Previous studies have identified several genetic loci associated with typical AF. We sought to identify common genetic variants underlying lone AF. This condition affects a subset of individuals without overt heart disease and with an increased heritability of AF. We report a meta-analysis of genome-wide association studies conducted using 1,335 individuals with lone AF (cases) and 12,844 unaffected individuals (referents). Cases were obtained from the German AF Network, Heart and Vascular Health Study, the Atherosclerosis Risk in Communities Study, the Cleveland Clinic and Massachusetts General Hospital. We identified an association on chromosome 1q21 to lone AF (rs13376333, adjusted odds ratio = 1.56; P = 6.3 × 10 12), and we replicated this association in two independent cohorts with lone AF (overall combined odds ratio = 1.52, 95% CI 1.40-1.64; P = 1.83 × 10 21). rs13376333 is intronic to KCNN3, which encodes a potassium channel protein involved in atrial repolarization.
Published: 2010
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39. Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function

Author: 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.
Published: 2010
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40. Genetic variants associated with cardiac structure and function: A meta-analysis and replication of genome-wide association data

Author: Vasan, R.S. (Ramachandran Srini), Glazer, N.L. (Nicole), Felix, J.F. (Janine), Lieb, W. (Wolfgang), Wild, P.S. (Philipp), Watzinger, N. (Norbert), Larson, M.G. (Martin), Smith, N.L. (Nicholas), Dehghan, A. (Abbas), Großhennig, A. (Anika), Schillert, A. (Arne), Teumer, A. (Alexander), Schmidt, R. (Reinhold), Kathiresan, S. (Sekar), Lumley, T. (Thomas), Aulchenko, Y.S. (Yurii), König, I.R. (Inke), Zeller, T. (Tanja), Homuth, G. (Georg), Struchalin, M.V. (Maksim), Aragam, J. (Jayashri), Bis, J.C. (Joshua), Rivadeneira Ramirez, F. (Fernando), Erdmann, J. (Jeanette), Schnabel, R. (Renate), Dörr, M. (Marcus), Zweiker, R. (Robert), Lind, L. (Lars), Rodeheffer, R.J. (Richard), Greiser, K.H. (Karin Halina), Levy, D. (Daniel), Haritunians, T. (Talin), Deckers, J.W. (Jaap), Stritzke, J. (Jan), Lackner, K.J. (Karl), Ingelsson, E. (Erik), Kullo, I. (Iftikhar), Haerting, J. (Johannes), Heckbert, S.R. (Susan), Stricker, B.H.Ch. (Bruno), Ziegler, A. (Andreas), Reffelmann, T. (Thorsten), Redfield, M.M. (Margaret), Mitchell, G.F. (Gary), Rice, K. (Kenneth), Arnett, D.K. (Donna), Hofman, A. (Albert), Gottdiener, J.S. (John), Uitterlinden, A.G. (André), Meitinger, T. (Thomas), Blettner, M. (Maria), Friedrich, N. (Nele), Wang, T.J. (Thomas), Psaty, B.M. (Bruce), Tikka-Kleemola, P. (Päivi), Wichmann, H.E. (Erich), Munzel, T. (Thomas), Kroemer, H.K. (Heyo), Benjamin, E.J. (Emelia), Rotter, J.I. (Jerome), Witteman, J.C.M. (Jacqueline), Schunkert, H. (Heribert), Völzke, H. (Henry), Blankenberg, S. (Stefan), O'Donnell, C.J. (Christopher), Völker, U. (Uwe), Werdan, K. (Karl), Vasan, R.S. (Ramachandran Srini), Glazer, N.L. (Nicole), Felix, J.F. (Janine), Lieb, W. (Wolfgang), Wild, P.S. (Philipp), Watzinger, N. (Norbert), Larson, M.G. (Martin), Smith, N.L. (Nicholas), Dehghan, A. (Abbas), Großhennig, A. (Anika), Schillert, A. (Arne), Teumer, A. (Alexander), Schmidt, R. (Reinhold), Kathiresan, S. (Sekar), Lumley, T. (Thomas), Aulchenko, Y.S. (Yurii), König, I.R. (Inke), Zeller, T. (Tanja), Homuth, G. (Georg), Struchalin, M.V. (Maksim), Aragam, J. (Jayashri), Bis, J.C. (Joshua), Rivadeneira Ramirez, F. (Fernando), Erdmann, J. (Jeanette), Schnabel, R. (Renate), Dörr, M. (Marcus), Zweiker, R. (Robert), Lind, L. (Lars), Rodeheffer, R.J. (Richard), Greiser, K.H. (Karin Halina), Levy, D. (Daniel), Haritunians, T. (Talin), Deckers, J.W. (Jaap), Stritzke, J. (Jan), Lackner, K.J. (Karl), Ingelsson, E. (Erik), Kullo, I. (Iftikhar), Haerting, J. (Johannes), Heckbert, S.R. (Susan), Stricker, B.H.Ch. (Bruno), Ziegler, A. (Andreas), Reffelmann, T. (Thorsten), Redfield, M.M. (Margaret), Mitchell, G.F. (Gary), Rice, K. (Kenneth), Arnett, D.K. (Donna), Hofman, A. (Albert), Gottdiener, J.S. (John), Uitterlinden, A.G. (André), Meitinger, T. (Thomas), Blettner, M. (Maria), Friedrich, N. (Nele), Wang, T.J. (Thomas), Psaty, B.M. (Bruce), Tikka-Kleemola, P. (Päivi), Wichmann, H.E. (Erich), Munzel, T. (Thomas), Kroemer, H.K. (Heyo), Benjamin, E.J. (Emelia), Rotter, J.I. (Jerome), Witteman, J.C.M. (Jacqueline), Schunkert, H. (Heribert), Völzke, H. (Henry), Blankenberg, S. (Stefan), O'Donnell, C.J. (Christopher), Völker, U. (Uwe), and Werdan, K. (Karl)
Abstract: Context: Echocardiographic measures of left ventricular (LV) structure and function are heritable phenotypes of cardiovascular disease. Objective: To identify common genetic variants associated with cardiac structure and function by conducting a meta-analysis of genome-wide association data in 5 population-based cohort studies (stage 1) with replication (stage 2) in 2 other community-based samples. Design, Setting, and Participants: Within each of 5 community-based cohorts comprising the EchoGen consortium (stage 1; n=12 612 individuals of European ancestry; 55% women, aged 26-95 years; examinations between 1978-2008), we estimated the association between approximately 2.5 million single-nucleotide polymorphisms (SNPs; imputed to the HapMap CEU panel) and echocardiographic traits. In stage 2, SNPs significantly associated with traits in stage 1 were tested for association in 2 other cohorts (n=4094 people of European ancestry). Using a prespecified P value threshold of 5 x 10-7to indicate genome-wide significance, we performed an inverse variance-weighted fixed-effects meta-analysis of genome-wide association data from each cohort. Main Outcome Measures: Echocardiographic traits: LV mass, internal dimensions, wall thickness, systolic dysfunction, aortic root, and left atrial size. Results: In stage 1, 16 genetic loci were associated with 5 echocardiographic traits: 1 each with LV internal dimensions and systolic dysfunction, 3 each with LV mass and wall thickness, and 8 with aortic root size. In stage 2, 5 loci replicated (6q22 locus associated with LV diastolic dimensions, explaining <1%of trait variance; 5q23, 12p12, 12q14, and 17p13 associated with aortic root size, explaining 1%-3% of trait variance). Conclusions: We identified 5 genetic loci harboring common variants that were associated with variation in LV diastolic dimensions and aortic root size, but such findings explained a very small proportion of variance. Further studies are required to replicate these
Published: 2009
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41. Genomewide association studies of stroke

Author: Ikram, M.A. (Arfan), Seshadri, S. (Sudha), Bis, J.C. (Joshua), Fornage, M. (Myriam), DeStefano, A.L. (Anita), Aulchenko, Y.S. (Yurii), Debette, S. (Stéphanie), Lumley, T. (Thomas), Folsom, A.R. (Aaron), Herik, E.G. (Evita) van den, Bos, M.J. (Michiel), Beiser, A. (Alexa), Cushman, M. (Mary Ann), Launer, L.J. (Lenore), Shahar, E. (Eyal), Struchalin, M.V. (Maksim), Du, Y. (Yangchun), Glazer, N.L. (Nicole), Rosamond, W.D. (Wayne), Rivadeneira Ramirez, F. (Fernando), Kelly-Hayes, M. (Margaret), Lopez, O.L. (Oscar), Coresh, J. (Josef), Hofman, A. (Albert), DeCarli, C. (Charles), Heckbert, S.R. (Susan), Koudstaal, P.J. (Peter), Yang, Q. (Qiong Fang), Smith, N.L. (Nicholas), Kase, C.S. (Carlos), Rice, K. (Kenneth), Haritunians, T. (Talin), Forey, F., Kort, P.L.M. (Paul) de, Taylor, K.D. (Kent), Lau, L.M.L. (Lonneke) de, Oostra, B.A. (Ben), Uitterlinden, A.G. (André), Rotter, J.I. (Jerome), Boerwinkle, E.A. (Eric), Psaty, B.M. (Bruce), Mosley, T.H. (Thomas), Duijn, C.M. (Cornelia) van, Breteler, M.M.B. (Monique), Longstreth Jr, W.T., Wolf, P.A. (Philip), Ikram, M.A. (Arfan), Seshadri, S. (Sudha), Bis, J.C. (Joshua), Fornage, M. (Myriam), DeStefano, A.L. (Anita), Aulchenko, Y.S. (Yurii), Debette, S. (Stéphanie), Lumley, T. (Thomas), Folsom, A.R. (Aaron), Herik, E.G. (Evita) van den, Bos, M.J. (Michiel), Beiser, A. (Alexa), Cushman, M. (Mary Ann), Launer, L.J. (Lenore), Shahar, E. (Eyal), Struchalin, M.V. (Maksim), Du, Y. (Yangchun), Glazer, N.L. (Nicole), Rosamond, W.D. (Wayne), Rivadeneira Ramirez, F. (Fernando), Kelly-Hayes, M. (Margaret), Lopez, O.L. (Oscar), Coresh, J. (Josef), Hofman, A. (Albert), DeCarli, C. (Charles), Heckbert, S.R. (Susan), Koudstaal, P.J. (Peter), Yang, Q. (Qiong Fang), Smith, N.L. (Nicholas), Kase, C.S. (Carlos), Rice, K. (Kenneth), Haritunians, T. (Talin), Forey, F., Kort, P.L.M. (Paul) de, Taylor, K.D. (Kent), Lau, L.M.L. (Lonneke) de, Oostra, B.A. (Ben), Uitterlinden, A.G. (André), Rotter, J.I. (Jerome), Boerwinkle, E.A. (Eric), Psaty, B.M. (Bruce), Mosley, T.H. (Thomas), Duijn, C.M. (Cornelia) van, Breteler, M.M.B. (Monique), Longstreth Jr, W.T., and Wolf, P.A. (Philip)
Abstract: BACKGROUND: The genes underlying the risk of stroke in the general population remain undetermined. METHODS: We carried out an analysis of genomewide association data generated from four large cohorts composing the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, including 19,602 white persons (mean [±SD] age, 63±8 years) in whom 1544 incident strokes (1164 ischemic strokes) developed over an average follow-up of 11 years. We tested the markers most strongly associated with stroke in a replication cohort of 2430 black persons with 215 incident strokes (191 ischemic strokes), another cohort of 574 black persons with 85 incident strokes (68 ischemic strokes), and 652 Dutch persons with ischemic stroke and 3613 unaffected persons. RESULTS: Two intergenic single-nucleotide polymorphisms on chromosome 12p13 and within 11 kb of the gene NINJ2 were associated with stroke (P<5×10-8). NINJ2 encodes an adhesion molecule expressed in glia and shows increased expression after nerve injury. Direct genotyping showed that rs12425791 was associated with an increased risk of total (i.e., all types) and ischemic stroke, with hazard ratios of 1.30 (95% confidence interval [CI], 1.19 to 1.42) and 1.33 (95% CI, 1.21 to 1.47), respectively, yielding population attributable risks of 11% and 12% in the discovery cohorts. Corresponding hazard ratios were 1.35 (95% CI, 1.01 to 1.79; P = 0.04) and 1.42 (95% CI, 1.06 to 1.91; P = 0.02) in the large cohort of black persons and 1.17 (95% CI, 1.01 to 1.37; P = 0.03) and 1.19 (95% CI, 1.01 to 1.41; P = 0.04) in the Dutch sample; the results of an underpowered analysis of the smaller black cohort were nonsignificant. CONCLUSIONS: A genetic locus on chromosome 12p13 is associated with an increased risk of stroke.
Published: 2009
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