17 results on '"Vaez, A. (Ahmad)"'
Search Results
2. Status of α-emitter Radioimmunoconjugates for Targeted Therapy
- Author
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Mobina, Rabiei, Vaez Alaei, Ahmad Reza, and Yousefnia, Hassan
- Abstract
This minireview describes the global situation of ongoing research and development and the clinical application of alpha emitter labeled immunoconjugates with various alpha emitters with an overview of the future trends. The potentially helpful alpha emitter radioisotopes for medical applications, chelators, and immunomolecules of interest for future alpha radioimmunotherapy are discussed. Challenges and some suggested future works on chelators are also presented.
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- 2023
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3. Bivariate genome-wide association analyses of the broad depression phenotype combined with major depressive disorder, bipolar disorder or schizophrenia reveal eight novel genetic loci for depression
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Amare, AT, Vaez, A. (Ahmad), Hsu, Y.-H. (Yi-Hsiang), Direk, N., Kamali, Z., Howard, D.M., Mcintosh, A.M. (Andrew), Tiemeier, H.W. (Henning), B?ltmann, U., Snieder, H. (Harold), Hartman, C. (Corina), Amare, AT, Vaez, A. (Ahmad), Hsu, Y.-H. (Yi-Hsiang), Direk, N., Kamali, Z., Howard, D.M., Mcintosh, A.M. (Andrew), Tiemeier, H.W. (Henning), B?ltmann, U., Snieder, H. (Harold), and Hartman, C. (Corina)
- Abstract
Although a genetic basis of depression has been well established in twin studies, identification of genome-wide significant loci has been difficult. We hypothesized that bivariate analyses of findings from a meta-analysis of genome-wide association studies (meta-GWASs) of the broad depression phenotype with those from meta-GWASs of self-reported and recurrent major depressive disorder (MDD), bipolar disorder and schizophrenia would enhance statistical power to identify novel genetic loci for depression. LD score regression analyses were first used to estimate the genetic correlations of broad depression with self-reported MDD, recurrent MDD, bipolar disorder and schizophrenia. Then, we performed four bivariate GWAS analyses. The genetic correlations (rg ± SE) of broad depression with self-reported MDD, recurrent MDD, bipolar disorder and schizophrenia were 0.79 ± 0.07, 0.24 ± 0.08, 0.53 ±
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- 2020
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4. The cardiac niche role in cardiomyocyte differentiation of rat bone marrow-derived stromal cells
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Vaez, Seyed Ahmad, Ebrahimi-Barough, Somayeh, Soleimani, Masoud, Kolivand, Sedighe, Farzamfar, Saeed, Ahmadi Tafti, Seyed Hossein, Azami, Mahmoud, Noorbakhsh, Farshid, and Ai, Jafar
- Subjects
stomatognathic system ,Cardiomyocyte isolation ,Differentiation ,Niche ,cardiovascular system ,Co-culture ,Microfluidic system ,Bone marrow-derived mesenchymal stromal cells (BMSCs) - Abstract
Due to the restricted potential of the heart to regenerate its damaged region, stem cell therapy is a promising treatment modality for myocardial infarction. It has been shown that incubation of bone marrow-derived stromal cells (BMSCs) with initial steps of cardiac differentiation in vitro, can have a significant effect on their therapeutic opotential to treat myocardial infarction. Based on these well-established principals we were encouraged to study the direct co-culture of rat BMSCs with neonatal mouse almost pure cardiomyocytes (APCs) and cardiac niche cells (CNCs) in static 2D and microfluidic cell culture systems. Our results showed that the difference regarding the beating rate in isolated APCs and CNCs in both 2D and the microfluidic system was not statistically significant for 30 days. No beat rate could be observed in induced BMSCs in all groups during experiment time. Except for BMSCs cultured alone in both experimental culture conditions, data obtained from Real-time PCR analysis showed that differentiated BMSCs in all co-cultured groups expressed GATA4, Nkx2.5, CX43, cTnI, cTnT, and β-MHC during 4 weeks. BMSCs demonstrated a higher expression of these cardiac factors in microfluidic chips than those co-cultured in 24 well plates. Moreover, immunocytochemistry (ICC), also revealed the GATA4 expression in differentiated BMSCs in all co-cultured groups. It was found that, when combined with shear stress, co-culture with cardiomyocyte can differentiate BMSCs significantly toward cardiomyocyte rather than co-culture alone., EXCLI Journal;Vol. 17 2018
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- 2018
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5. Erratum to: Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits
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Evangelou, E. (Evangelos), Warren, H. (Helen), Mosen-Ansorena, D. (David), Mifsud, B. (Borbala), Pazoki, R. (Raha), Gao, H. (He), Ntritsos, G. (Georgios), Dimou, N. (Niki), Cabrera, C.P. (Claudia P.), Karaman, I. (Ibrahim), Ng, F.L. (Fu Liang), Evangelou, M. (Marina), Witkowska, K. (Katarzyna), Tzanis, E. (Evan), Hellwege, J.N. (Jacklyn N.), Giri, A. (Ayush), Velez Edwards, D.R. (Digna R.), Sun, Y.V. (Yan V.), Cho, K. (Kelly), Gaziano, J.M. (J. Michael), Wilson, P.W.F. (Peter W. F.), Tsao, P.S. (Philip S.), Kovesdy, C.P. (Csaba P.), Esko, T. (Tonu), Mägi, R. (Reedik), Milani, L. (Lili), Almgren, P. (Peter), Boutin, T. (Thibaud), Debette, S. (Stéphanie), Ding, J. (Jun), Giulianini, F. (Franco), Holliday, E.G. (Elizabeth), Jackson, A.U. (Anne), Li-Gao, R. (Ruifang), Lin, W.-Y. (Wei-Yu), Luan, J., Mangino, M. (Massimo), Oldmeadow, C. (Christopher), Prins, B.P. (Bram Peter), Qian, Y. (Yong), Sargurupremraj, M. (Muralidharan), Shah, N. (Nisha), Surendran, P. (Praveen), Thériault, S. (Sébastien), Verweij, N. (Niek), Willems, S.M. (Sara), Zhao, J.-H. (Jing-Hua), Amouyel, P. (Philippe), Connell, J. (John), Mutsert, R. (Reneé) de, Doney, A.S.F. (Alex), Farrall, M. (Martin), Menni, C. (Cristina), Morris, A.D. (Andrew), Noordam, R. (Raymond), Pare, G. (Guillame), Poulter, N.R. (Neil), Shields, D.C. (Denis C.), Stanton, A. (Alice), McG Thom, S.A., Abecasis, G. (Gonçalo), Amin, N. (Najaf), Arking, D.E. (Dan), Ayers, K.L. (Kristin), Barbieri, C.M. (Caterina M.), Batini, C. (Chiara), Bis, J.C. (Joshua), Blake, T. (Tineka), Bochud, M. (Murielle), Boehnke, M. (Michael), Boerwinkle, E. (Eric), Boomsma, D.I. (Dorret I.), Bottinger, E.P. (Erwin P.), Braund, P.S. (Peter), Brumat, M. (Marco), Campbell, A. (Archie), Campbell, H. (Harry), Chakravarti, A. (Aravinda), Chambers, J.C. (John C.), Chauhan, G. (Ganesh), Ciullo, M. (Marina), Cocca, M. (Massimiliano), Collins, F. (Francis), Cordell, H.J. (Heather), Davies, G. (Gail), de Borst, M.H. (Martin H.), Geus, E.J.C. (Eco) de, Deary, I.J. (Ian), Deelen, J. (Joris), Del Greco M, F. (Fabiola), Demirkale, C.Y. (Cumhur Yusuf), Dörr, M. (Marcus), Ehret, G.B. (Georg B.), Elosua, R. (Roberto), Enroth, S. (Stefan), Erzurumluoglu, A.M. (A. Mesut), Ferreira, T. (Teresa), Frånberg, M. (Mattias), Franco, O.H. (Oscar), Gandin, I. (Ilaria), Gasparini, P. (Paolo), Giedraitis, V. (Vilmantas), Gieger, C. (Christian), Girotto, G. (Giorgia), Goel, A. (Anuj), Gow, A.J. (Alan J.), Gudnason, V. (Vilmundur), Guo, X. (Xiuqing), Gyllensten, U. (Ulf), Hamsten, A. (Anders), Harris, T.B. (Tamara), Harris, S.E. (Sarah), Hartman, C.A. (Catharina A.), Havulinna, A.S. (Aki), Hicks, A.A. (Andrew A.), Hofer, E. (Edith), Hofman, A. (Albert), Hottenga, J.J. (Jouke Jan), Huffman, J.E. (Jennifer E.), Hwang, S.-J. (Shih-Jen), Ingelsson, E. (Erik), James, A. (Alan), Jansen, R. (Rick), Jarvelin, M.-R. (Marjo-Riitta), Joehanes, R. (Roby), Johansson, A. (Åsa), Johnson, A.D. (Andrew), Joshi, P.K. (Peter K.), Jousilahti, P. (Pekka), Jukema, J.W. (Jan Wouter), Jula, A. (Antti), Kähönen, M. (Mika), Kathiresan, S. (Sekar), Keavney, B.D. (Bernard D.), Khaw, K.-T. (Kay-Tee), Knekt, P., Knight, J. (Joanne), Kolcic, I. (Ivana), Kooner, J.S. (Jaspal S.), Koskinen, S. (Seppo), Kristiansson, K. (Kati), Kutalik, Z. (Zoltán), Laan, M. (Maris), Larson, M.G. (Martin), Launer, L.J. (Lenore), Lehne, B. (Benjamin), Lehtimäki, T. (Terho), Liewald, D.C.M. (David C. M.), Lin, L. (Li), Kao, W.H.L. (Wen), Lindgren, C.M. (Cecilia M.), Liu, Y. (YongMei), Loos, R.J.F. (Ruth), Lopez, L.M. (Lorna), Lu, Y. (Yingchang), Lyytikäinen, L.-P. (Leo-Pekka), Mahajan, A. (Anubha), Mamasoula, C. (Chrysovalanto), Marrugat, J. (Jaume), Marten, J. (Jonathan), Milaneschi, Y. (Yuri), Morgan, A. (Anna), Morris, A.P. (Andrew), Morrison, A.C. (Alanna), Munson, P.J. (Peter), Nalls, M.A. (Michael), Nandakumar, P. (Priyanka), Nelson, C.P. (Christopher P.), Niiranen, T. (Teemu), Nolte, I.M. (Ilja), Nutile, T. (Teresa), Oldehinkel, A.J. (Albertine), Oostra, B.A. (Ben), O’Reilly, P.F. (Paul F.), Org, E. (Elin), Padmanabhan, S. (Sandosh), Palmas, W. (Walter), Palotie, A. (Aarno), Pattie, A. (Alison), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Peters, A. (Annette), Polasek, O. (Ozren), Pramstaller, P.P. (Peter Paul), Nguyen, Q.T. (Quang Tri), Raitakari, O. (Olli), Ren, M. (Meixia), Rettig, R. (Rainer), Rice, K.M. (Kenneth), Ridker, P.M. (Paul), Ried, J.S. (Janina S.), Riese, H. (Harriëtte), Ripatti, S. (Samuli), Robino, A. (Antonietta), Rose, L.M. (Lynda M.), Rotter, J.I. (Jerome I.), Rudan, I. (Igor), Ruggiero, D., Saba, Y. (Yasaman), Sala, C. (Cinzia), Salomaa, V. (Veikko), Samani, N.J. (Nilesh J.), Sarin, A.-P., Schmidt, R. (Reinhold), Schmidt, H. (Helena), Shrine, N.R.G. (Nick), Siscovick, D. (David), Smith, A.V. (Albert), Snieder, H. (Harold), Sõber, S. (Siim), Sorice, R., Starr, J.M. (John), Stott, D.J. (David. J.), Strachan, D.P. (David), Strawbridge, R.J. (Rona), Sundström, J. (Johan), Swertz, M.A. (Morris A.), Taylor, K.D. (Kent), Teumer, A. (Alexander), Tobin, M.D. (Martin), Tomaszewski, M. (Maciej), Toniolo, D. (Daniela), Traglia, M. (Michela), Trompet, S. (Stella), Tuomilehto, J. (Jaakko), Tzourio, C. (Christophe), Uitterlinden, A.G. (André), Vaez, A. (Ahmad), Most, P.J. (Peter) van der, Duijn, C.M. (Cornelia) van, Vergnaud, A.-C. (Anne-Claire), Verwoert, G.C. (Germaine C.), Vitart, V. (Veronique), Völker, U. (Uwe), Vollenweider, P. (Peter), Vuckovic, D. (Dragana), Watkins, H. (Hugh), Wild, S.H. (Sarah), Willemsen, G. (Gonneke), Wilson, J.F. (James F.), Wright, A.F. (Alan), Yao, J. (Jie), Zemunik, T. (Tatijana), Zhang, W. (Weihua), Attia, J. (John), Butterworth, A.S. (Adam S.), Chasman, D.I. (Daniel), Conen, D. (David), Cucca, F. (Francesco), Danesh, J. (John), Hayward, C. (Caroline), Howson, J.M.M. (Joanna M. M.), Laakso, M. (Markku), Lakatta, E.G. (Edward G.), Langenberg, C. (Claudia), Melander, O. (Olle), Mook-Kanamori, D.O. (Dennis O.), Palmer, C.N.A. (Colin N. A.), Risch, L. (Lorenz), Scott, R.A. (Robert), Scott, R.J. (Rodney J.), Sever, P. (Peter), Spector, T.D. (Timothy), van der Harst, P. (Pim), Wareham, N.J. (Nick), Zeggini, E. (Eleftheria), Levy, D. (Daniel), Munroe, P. (Patricia), Newton-Cheh, C. (Christopher), Brown, M.J. (Morris), Metspalu, A. (Andres), Hung, A.M. (Adriana M.), Ódonnell, C.J. (Christopher), Edwards, T.L. (Todd L.), Psaty, B.M. (Bruce), Tzoulaki, I., Barnes, M.J. (Michael), Wain, L.V. (Louise V.), Elliott, P. (Paul), Caulfield, M. (Mark), Evangelou, E. (Evangelos), Warren, H. (Helen), Mosen-Ansorena, D. (David), Mifsud, B. (Borbala), Pazoki, R. (Raha), Gao, H. (He), Ntritsos, G. (Georgios), Dimou, N. (Niki), Cabrera, C.P. (Claudia P.), Karaman, I. (Ibrahim), Ng, F.L. (Fu Liang), Evangelou, M. (Marina), Witkowska, K. (Katarzyna), Tzanis, E. (Evan), Hellwege, J.N. (Jacklyn N.), Giri, A. (Ayush), Velez Edwards, D.R. (Digna R.), Sun, Y.V. (Yan V.), Cho, K. (Kelly), Gaziano, J.M. (J. Michael), Wilson, P.W.F. (Peter W. F.), Tsao, P.S. (Philip S.), Kovesdy, C.P. (Csaba P.), Esko, T. (Tonu), Mägi, R. (Reedik), Milani, L. (Lili), Almgren, P. (Peter), Boutin, T. (Thibaud), Debette, S. (Stéphanie), Ding, J. (Jun), Giulianini, F. (Franco), Holliday, E.G. (Elizabeth), Jackson, A.U. (Anne), Li-Gao, R. (Ruifang), Lin, W.-Y. (Wei-Yu), Luan, J., Mangino, M. (Massimo), Oldmeadow, C. (Christopher), Prins, B.P. (Bram Peter), Qian, Y. (Yong), Sargurupremraj, M. (Muralidharan), Shah, N. (Nisha), Surendran, P. (Praveen), Thériault, S. (Sébastien), Verweij, N. (Niek), Willems, S.M. (Sara), Zhao, J.-H. (Jing-Hua), Amouyel, P. (Philippe), Connell, J. (John), Mutsert, R. (Reneé) de, Doney, A.S.F. (Alex), Farrall, M. (Martin), Menni, C. (Cristina), Morris, A.D. (Andrew), Noordam, R. (Raymond), Pare, G. (Guillame), Poulter, N.R. (Neil), Shields, D.C. (Denis C.), Stanton, A. (Alice), McG Thom, S.A., Abecasis, G. (Gonçalo), Amin, N. (Najaf), Arking, D.E. (Dan), Ayers, K.L. (Kristin), Barbieri, C.M. (Caterina M.), Batini, C. (Chiara), Bis, J.C. (Joshua), Blake, T. (Tineka), Bochud, M. (Murielle), Boehnke, M. (Michael), Boerwinkle, E. (Eric), Boomsma, D.I. (Dorret I.), Bottinger, E.P. (Erwin P.), Braund, P.S. (Peter), Brumat, M. (Marco), Campbell, A. (Archie), Campbell, H. (Harry), Chakravarti, A. (Aravinda), Chambers, J.C. (John C.), Chauhan, G. (Ganesh), Ciullo, M. (Marina), Cocca, M. (Massimiliano), Collins, F. (Francis), Cordell, H.J. (Heather), Davies, G. (Gail), de Borst, M.H. (Martin H.), Geus, E.J.C. (Eco) de, Deary, I.J. (Ian), Deelen, J. (Joris), Del Greco M, F. (Fabiola), Demirkale, C.Y. (Cumhur Yusuf), Dörr, M. (Marcus), Ehret, G.B. (Georg B.), Elosua, R. (Roberto), Enroth, S. (Stefan), Erzurumluoglu, A.M. (A. Mesut), Ferreira, T. (Teresa), Frånberg, M. (Mattias), Franco, O.H. (Oscar), Gandin, I. (Ilaria), Gasparini, P. (Paolo), Giedraitis, V. (Vilmantas), Gieger, C. (Christian), Girotto, G. (Giorgia), Goel, A. (Anuj), Gow, A.J. (Alan J.), Gudnason, V. (Vilmundur), Guo, X. (Xiuqing), Gyllensten, U. (Ulf), Hamsten, A. (Anders), Harris, T.B. (Tamara), Harris, S.E. (Sarah), Hartman, C.A. (Catharina A.), Havulinna, A.S. (Aki), Hicks, A.A. (Andrew A.), Hofer, E. (Edith), Hofman, A. (Albert), Hottenga, J.J. (Jouke Jan), Huffman, J.E. (Jennifer E.), Hwang, S.-J. (Shih-Jen), Ingelsson, E. (Erik), James, A. (Alan), Jansen, R. (Rick), Jarvelin, M.-R. (Marjo-Riitta), Joehanes, R. (Roby), Johansson, A. (Åsa), Johnson, A.D. (Andrew), Joshi, P.K. (Peter K.), Jousilahti, P. (Pekka), Jukema, J.W. (Jan Wouter), Jula, A. (Antti), Kähönen, M. (Mika), Kathiresan, S. (Sekar), Keavney, B.D. (Bernard D.), Khaw, K.-T. (Kay-Tee), Knekt, P., Knight, J. (Joanne), Kolcic, I. (Ivana), Kooner, J.S. (Jaspal S.), Koskinen, S. (Seppo), Kristiansson, K. (Kati), Kutalik, Z. (Zoltán), Laan, M. (Maris), Larson, M.G. (Martin), Launer, L.J. (Lenore), Lehne, B. (Benjamin), Lehtimäki, T. (Terho), Liewald, D.C.M. (David C. M.), Lin, L. (Li), Kao, W.H.L. (Wen), Lindgren, C.M. (Cecilia M.), Liu, Y. (YongMei), Loos, R.J.F. (Ruth), Lopez, L.M. (Lorna), Lu, Y. (Yingchang), Lyytikäinen, L.-P. (Leo-Pekka), Mahajan, A. (Anubha), Mamasoula, C. (Chrysovalanto), Marrugat, J. (Jaume), Marten, J. (Jonathan), Milaneschi, Y. (Yuri), Morgan, A. (Anna), Morris, A.P. (Andrew), Morrison, A.C. (Alanna), Munson, P.J. (Peter), Nalls, M.A. (Michael), Nandakumar, P. (Priyanka), Nelson, C.P. (Christopher P.), Niiranen, T. (Teemu), Nolte, I.M. (Ilja), Nutile, T. (Teresa), Oldehinkel, A.J. (Albertine), Oostra, B.A. (Ben), O’Reilly, P.F. (Paul F.), Org, E. (Elin), Padmanabhan, S. (Sandosh), Palmas, W. (Walter), Palotie, A. (Aarno), Pattie, A. (Alison), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Peters, A. (Annette), Polasek, O. (Ozren), Pramstaller, P.P. (Peter Paul), Nguyen, Q.T. (Quang Tri), Raitakari, O. (Olli), Ren, M. (Meixia), Rettig, R. (Rainer), Rice, K.M. (Kenneth), Ridker, P.M. (Paul), Ried, J.S. (Janina S.), Riese, H. (Harriëtte), Ripatti, S. (Samuli), Robino, A. (Antonietta), Rose, L.M. (Lynda M.), Rotter, J.I. (Jerome I.), Rudan, I. (Igor), Ruggiero, D., Saba, Y. (Yasaman), Sala, C. (Cinzia), Salomaa, V. (Veikko), Samani, N.J. (Nilesh J.), Sarin, A.-P., Schmidt, R. (Reinhold), Schmidt, H. (Helena), Shrine, N.R.G. (Nick), Siscovick, D. (David), Smith, A.V. (Albert), Snieder, H. (Harold), Sõber, S. (Siim), Sorice, R., Starr, J.M. (John), Stott, D.J. (David. J.), Strachan, D.P. (David), Strawbridge, R.J. (Rona), Sundström, J. (Johan), Swertz, M.A. (Morris A.), Taylor, K.D. (Kent), Teumer, A. (Alexander), Tobin, M.D. (Martin), Tomaszewski, M. (Maciej), Toniolo, D. (Daniela), Traglia, M. (Michela), Trompet, S. (Stella), Tuomilehto, J. (Jaakko), Tzourio, C. (Christophe), Uitterlinden, A.G. (André), Vaez, A. (Ahmad), Most, P.J. (Peter) van der, Duijn, C.M. (Cornelia) van, Vergnaud, A.-C. (Anne-Claire), Verwoert, G.C. (Germaine C.), Vitart, V. (Veronique), Völker, U. (Uwe), Vollenweider, P. (Peter), Vuckovic, D. (Dragana), Watkins, H. (Hugh), Wild, S.H. (Sarah), Willemsen, G. (Gonneke), Wilson, J.F. (James F.), Wright, A.F. (Alan), Yao, J. (Jie), Zemunik, T. (Tatijana), Zhang, W. (Weihua), Attia, J. (John), Butterworth, A.S. (Adam S.), Chasman, D.I. (Daniel), Conen, D. (David), Cucca, F. (Francesco), Danesh, J. (John), Hayward, C. (Caroline), Howson, J.M.M. (Joanna M. M.), Laakso, M. (Markku), Lakatta, E.G. (Edward G.), Langenberg, C. (Claudia), Melander, O. (Olle), Mook-Kanamori, D.O. (Dennis O.), Palmer, C.N.A. (Colin N. A.), Risch, L. (Lorenz), Scott, R.A. (Robert), Scott, R.J. (Rodney J.), Sever, P. (Peter), Spector, T.D. (Timothy), van der Harst, P. (Pim), Wareham, N.J. (Nick), Zeggini, E. (Eleftheria), Levy, D. (Daniel), Munroe, P. (Patricia), Newton-Cheh, C. (Christopher), Brown, M.J. (Morris), Metspalu, A. (Andres), Hung, A.M. (Adriana M.), Ódonnell, C.J. (Christopher), Edwards, T.L. (Todd L.), Psaty, B.M. (Bruce), Tzoulaki, I., Barnes, M.J. (Michael), Wain, L.V. (Louise V.), Elliott, P. (Paul), and Caulfield, M. (Mark)
- Abstract
In the version of this article originally published, the name of author Martin H. de Borst was coded incorrectly in the XML. The error has now been corrected in the HTML version of the paper.
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- 2018
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6. Bioinformatics of genomic association mapping
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Vaez Barzani, Ahmad, Vaez Barzani, Ahmad, Vaez Barzani, Ahmad, and Vaez Barzani, Ahmad
- Abstract
In this thesis we present an overview of bioinformatics-based approaches for genomic association mapping, with emphasis on human quantitative traits and their contribution to complex diseases. We aim to provide a comprehensive walk-through of the classic steps of genomic association mapping illustrating the application and development of bioinformatics tools along the way. We start with a classic heritability study, continue with providing novel tools for genome-wide association studies (GWASs) of complex traits, and end with an integrated post-GWAS pipeline for translating GWAS findings of any human trait or disease to biological knowledge. Using this A-to-Z approach, we emphasize the importance of following the consecutive steps of genomic association mapping. To show how bioinformatics tools can facilitate and support analysis of high-throughput biological data, in Chapters 2, 3, 5, 6, and 7 we applied a number of already available tools, whereas in Chapters 3, 4, and 7 we developed novel bioinformatics tools supporting appropriate analysis of “big data” for genomic association mapping. Our in-house developed and extensively documented bioinformatics tools are freely available to the scientific community for further use. Furthermore, and as a running example of genomic association mapping of a typical human complex trait, we strictly adhered to serum levels of C-reactive protein (CRP). Using appropriate bioinformatics-based tools, either already available or our in-house developed ones, we succeeded to gain in knowledge of biological mechanisms controlling serum levels of CRP as well as its (causal) contribution to the pathophysiology of human diseases.
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- 2015
7. Genetic loci associated with heart rate variability and their effects on cardiac disease risk
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Nolte, I. M. (Ilja M.), Munoz, M. L. (M. Loretto), Tragante, V. (Vinicius), Amare, A. T. (Azmeraw T.), Jansen, R. (Rick), Vaez, A. (Ahmad), von der Heyde, B. (Benedikt), Avery, C. L. (Christy L.), Bis, J. C. (Joshua C.), Dierckx, B. (Bram), van Dongen, J. (Jenny), Gogarten, S. M. (Stephanie M.), Goyette, P. (Philippe), Hernesniemi, J. (Jussi), Huikari, V. (Ville), Hwang, S.-J. (Shih-Jen), Jaju, D. (Deepali), Kerr, K. F. (Kathleen F.), Kluttig, A. (Alexander), Krijthe, B. P. (Bouwe P.), Kumar, J. (Jitender), van der Laan, S. W. (Sander W.), Lyytikäinen, L.-P. (Leo-Pekka), Maihofer, A. X. (Adam X.), Minassian, A. (Arpi), van der Most, P. J. (Peter J.), Mueller-Nurasyid, M. (Martina), Nivard, M. (Michel), Salvi, E. (Erika), Stewart, J. D. (James D.), Thayer, J. F. (Julian F.), Verweij, N. (Niek), Wong, A. (Andrew), Zabaneh, D. (Delilah), Zafarmand, M. H. (Mohammad H.), Abdellaoui, A. (Abdel), Albarwani, S. (Sulayma), Albert, C. (Christine), Alonso, A. (Alvaro), Ashar, F. (Foram), Auvinen, J. (Juha), Axelsson, T. (Tomas), Baker, D. G. (Dewleen G.), de Bakker, P. I. (Paul I. W.), Barcella, M. (Matteo), Bayoumi, R. (Riad), Bieringa, R. J. (Rob J.), Boomsma, D. (Dorret), Boucher, G. (Gabrielle), Britton, A. R. (Annie R.), Christophersen, I. E. (Ingrid E.), Dietrich, A. (Andrea), Ehret, G. B. (George B.), Ellinor, P. T. (Patrick T.), Eskola, M. (Markku), Felix, J. F. (Janine F.), Floras, J. S. (John S.), Franco, O. H. (Oscar H.), Friberg, P. (Peter), Gademan, M. G. (Maaike G. J.), Geyer, M. A. (Mark A.), Giedraitis, V. (Vilmantas), Hartman, C. A. (Catharina A.), Hemerich, D. (Daiane), Hofman, A. (Albert), Hottenga, J.-J. (Jouke-Jan), Huikuri, H. (Heikki), Hutri-Kähönen, N. (Nina), Jouven, X. (Xavier), Junttila, J. (Juhani), Juonala, M. (Markus), Kiviniemi, A. M. (Antti M.), Kors, J. A. (Jan A.), Kumari, M. (Meena), Kuznetsova, T. (Tatiana), Laurie, C. C. (Cathy C.), Lefrandt, J. D. (Joop D.), Li, Y. (Yong), Li, Y. (Yun), Liao, D. (Duanping), Limacher, M. C. (Marian C.), Lin, H. J. (Henry J.), Lindgren, C. M. (Cecilia M.), Lubitz, S. A. (Steven A.), Mahajan, A. (Anubha), McKnight, B. (Barbara), zu Schwabedissen, H. M. (Henriette Meyer), Milaneschi, Y. (Yuri), Mononen, N. (Nina), Morris, A. P. (Andrew P.), Nalls, M. A. (Mike A.), Navis, G. (Gerjan), Neijts, M. (Melanie), Nikus, K. (Kjell), North, K. E. (Kari E.), O'Connor, D. T. (Daniel T.), Ormel, J. (Johan), Perz, S. (Siegfried), Peters, A. (Annette), Psaty, B. M. (Bruce M.), Raitakari, O. T. (Olli T.), Risbrough, V. B. (Victoria B.), Sinner, M. F. (Moritz F.), Siscovick, D. (David), Smit, J. H. (Johannes H.), Smith, N. L. (Nicholas L.), Soliman, E. Z. (Elsayed Z.), Sotoodehnia, N. (Nona), Staessen, J. A. (Jan A.), Stein, P. K. (Phyllis K.), Stilp, A. M. (Adrienne M.), Stolarz-Skrzypek, K. (Katarzyna), Strauch, K. (Konstantin), Sundström, J. (Johan), Swenne, C. A. (Cees A.), Syvänen, A.-C. (Ann-Christine), Tardif, J.-C. (Jean-Claude), Taylor, K. D. (Kent D.), Teumer, A. (Alexander), Thornton, T. A. (Timothy A.), Tinker, L. E. (Lesley E.), Uitterlinden, A. G. (Andre G.), van Setten, J. (Jessica), Voss, A. (Andreas), Waldenberger, M. (Melanie), Wilhelmsen, K. C. (Kirk C.), Willemsen, G. (Gonneke), Wong, Q. (Quenna), Zhang, Z.-M. (Zhu-Ming), Zonderman, A. B. (Alan B.), Cusi, D. (Daniele), Evans, M. K. (Michele K.), Greiser, H. K. (Halina K.), van der Harst, P. (Pim), Hassan, M. (Mohammad), Ingelsson, E. (Erik), Järvelin, M.-R. (Marjo-Riitta), Kaab, S. (Stefan), Kähönen, M. (Mika), Kivimäki, M. (Mika), Kooperberg, C. (Charles), Kuh, D. (Diana), Lehtimäki, T. (Terho), Lind, L. (Lars), Nievergelt, C. M. (Caroline M.), O'Donnell, C. J. (Chris J.), Oldehinkel, A. J. (Albertine J.), Penninx, B. (Brenda), Reiner, A. P. (Alexander P.), Riese, H. (Harriette), van Roon, A. M. (Arie M.), Rioux, J. D. (John D.), Rotter, J. I. (Jerome I.), Sofer, T. (Tamar), Stricker, B. H. (Bruno H.), Tiemeier, H. (Henning), Vrijkotte, T. G. (Tanja G. M.), Asselbergs, F. W. (Folkert W.), Brundel, B. J. (Bianca J. J. M.), Heckbert, S. R. (Susan R.), Whitsel, E. A. (Eric A.), den Hoed, M. (Marcel), Snieder, H. (Harold), de Geus, E. J. (Eco J. C.), Nolte, I. M. (Ilja M.), Munoz, M. L. (M. Loretto), Tragante, V. (Vinicius), Amare, A. T. (Azmeraw T.), Jansen, R. (Rick), Vaez, A. (Ahmad), von der Heyde, B. (Benedikt), Avery, C. L. (Christy L.), Bis, J. C. (Joshua C.), Dierckx, B. (Bram), van Dongen, J. (Jenny), Gogarten, S. M. (Stephanie M.), Goyette, P. (Philippe), Hernesniemi, J. (Jussi), Huikari, V. (Ville), Hwang, S.-J. (Shih-Jen), Jaju, D. (Deepali), Kerr, K. F. (Kathleen F.), Kluttig, A. (Alexander), Krijthe, B. P. (Bouwe P.), Kumar, J. (Jitender), van der Laan, S. W. (Sander W.), Lyytikäinen, L.-P. (Leo-Pekka), Maihofer, A. X. (Adam X.), Minassian, A. (Arpi), van der Most, P. J. (Peter J.), Mueller-Nurasyid, M. (Martina), Nivard, M. (Michel), Salvi, E. (Erika), Stewart, J. D. (James D.), Thayer, J. F. (Julian F.), Verweij, N. (Niek), Wong, A. (Andrew), Zabaneh, D. (Delilah), Zafarmand, M. H. (Mohammad H.), Abdellaoui, A. (Abdel), Albarwani, S. (Sulayma), Albert, C. (Christine), Alonso, A. (Alvaro), Ashar, F. (Foram), Auvinen, J. (Juha), Axelsson, T. (Tomas), Baker, D. G. (Dewleen G.), de Bakker, P. I. (Paul I. W.), Barcella, M. (Matteo), Bayoumi, R. (Riad), Bieringa, R. J. (Rob J.), Boomsma, D. (Dorret), Boucher, G. (Gabrielle), Britton, A. R. (Annie R.), Christophersen, I. E. (Ingrid E.), Dietrich, A. (Andrea), Ehret, G. B. (George B.), Ellinor, P. T. (Patrick T.), Eskola, M. (Markku), Felix, J. F. (Janine F.), Floras, J. S. (John S.), Franco, O. H. (Oscar H.), Friberg, P. (Peter), Gademan, M. G. (Maaike G. J.), Geyer, M. A. (Mark A.), Giedraitis, V. (Vilmantas), Hartman, C. A. (Catharina A.), Hemerich, D. (Daiane), Hofman, A. (Albert), Hottenga, J.-J. (Jouke-Jan), Huikuri, H. (Heikki), Hutri-Kähönen, N. (Nina), Jouven, X. (Xavier), Junttila, J. (Juhani), Juonala, M. (Markus), Kiviniemi, A. M. (Antti M.), Kors, J. A. (Jan A.), Kumari, M. (Meena), Kuznetsova, T. (Tatiana), Laurie, C. C. (Cathy C.), Lefrandt, J. D. (Joop D.), Li, Y. (Yong), Li, Y. (Yun), Liao, D. (Duanping), Limacher, M. C. (Marian C.), Lin, H. J. (Henry J.), Lindgren, C. M. (Cecilia M.), Lubitz, S. A. (Steven A.), Mahajan, A. (Anubha), McKnight, B. (Barbara), zu Schwabedissen, H. M. (Henriette Meyer), Milaneschi, Y. (Yuri), Mononen, N. (Nina), Morris, A. P. (Andrew P.), Nalls, M. A. (Mike A.), Navis, G. (Gerjan), Neijts, M. (Melanie), Nikus, K. (Kjell), North, K. E. (Kari E.), O'Connor, D. T. (Daniel T.), Ormel, J. (Johan), Perz, S. (Siegfried), Peters, A. (Annette), Psaty, B. M. (Bruce M.), Raitakari, O. T. (Olli T.), Risbrough, V. B. (Victoria B.), Sinner, M. F. (Moritz F.), Siscovick, D. (David), Smit, J. H. (Johannes H.), Smith, N. L. (Nicholas L.), Soliman, E. Z. (Elsayed Z.), Sotoodehnia, N. (Nona), Staessen, J. A. (Jan A.), Stein, P. K. (Phyllis K.), Stilp, A. M. (Adrienne M.), Stolarz-Skrzypek, K. (Katarzyna), Strauch, K. (Konstantin), Sundström, J. (Johan), Swenne, C. A. (Cees A.), Syvänen, A.-C. (Ann-Christine), Tardif, J.-C. (Jean-Claude), Taylor, K. D. (Kent D.), Teumer, A. (Alexander), Thornton, T. A. (Timothy A.), Tinker, L. E. (Lesley E.), Uitterlinden, A. G. (Andre G.), van Setten, J. (Jessica), Voss, A. (Andreas), Waldenberger, M. (Melanie), Wilhelmsen, K. C. (Kirk C.), Willemsen, G. (Gonneke), Wong, Q. (Quenna), Zhang, Z.-M. (Zhu-Ming), Zonderman, A. B. (Alan B.), Cusi, D. (Daniele), Evans, M. K. (Michele K.), Greiser, H. K. (Halina K.), van der Harst, P. (Pim), Hassan, M. (Mohammad), Ingelsson, E. (Erik), Järvelin, M.-R. (Marjo-Riitta), Kaab, S. (Stefan), Kähönen, M. (Mika), Kivimäki, M. (Mika), Kooperberg, C. (Charles), Kuh, D. (Diana), Lehtimäki, T. (Terho), Lind, L. (Lars), Nievergelt, C. M. (Caroline M.), O'Donnell, C. J. (Chris J.), Oldehinkel, A. J. (Albertine J.), Penninx, B. (Brenda), Reiner, A. P. (Alexander P.), Riese, H. (Harriette), van Roon, A. M. (Arie M.), Rioux, J. D. (John D.), Rotter, J. I. (Jerome I.), Sofer, T. (Tamar), Stricker, B. H. (Bruno H.), Tiemeier, H. (Henning), Vrijkotte, T. G. (Tanja G. M.), Asselbergs, F. W. (Folkert W.), Brundel, B. J. (Bianca J. J. M.), Heckbert, S. R. (Susan R.), Whitsel, E. A. (Eric A.), den Hoed, M. (Marcel), Snieder, H. (Harold), and de Geus, E. J. (Eco J. C.)
- Abstract
Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (-0.74
- Published
- 2017
8. The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals
- Author
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Ehret, G.B. (Georg), Ferreira, T. (Teresa), Chasman, D.I. (Daniel), Jackson, A.U. (Anne), Schmidt, E.M. (Ellen), Johnson, T. (Toby), Thorleifsson, G. (Gudmar), Luan, J. (Jian'An), Donnelly, L.A. (Louise), Kanoni, S. (Stavroula), Petersen, A.K., Pihur, V. (Vasyl), Strawbridge, R.J. (Rona), Shungin, D. (Dmitry), Hughes, M.F. (Maria F.), Meirelles, O., Kaakinen, M. (Marika), Bouatia-Naji, N. (Nabila), Kristiansson, K. (Kati), Shah, S. (Sonia), Kleber, M.E. (Marcus), Guo, X. (Xiuqing), Lyytikäinen, L.-P. (Leo-Pekka), Fava, C. (Cristiano), Eriksson, N. (Niclas), Nolte, I.M. (Ilja), Magnusson, P.K. (Patrik), Salfati, E. (Elias), Rallidis, L.S. (Loukianos), Theusch, E. (Elizabeth), Smith, A.J. (Andrew), Folkersen, L. (Lasse), Witkowska, H.E. (Ewa), Pers, T.H. (Tune), Joehanes, R. (Roby), Kim, S.K. (Stuart K.), Lataniotis, L. (Lazaros), Jansen, R., Johnson, A.D. (Andrew), Warren, H. (Helen), Kim, Y.J., Zhao, W. (Wei), Wu, Y. (Ying), Tayo, B. (Bamidele), Bochud, M. (Murielle), Absher, D. (Devin), Adair, L.S. (Linda), Amin, N. (Najaf), Arking, D.E. (Dan), Axelsson, T. (Tomas), Baldassarre, D. (Damiano), Balkau, B. (Beverley), Bandinelli, S. (Stefania), Barnes, M.J. (Michael), Barroso, I.E. (Inês), Bevan, S. (Stephen), Bis, J.C. (Joshua), Bjornsdottir, G. (Gyda), Boehnke, M. (Michael), Boerwinkle, E.A. (Eric), Bonnycastle, L.L. (Lori), Boomsma, D.I. (Dorret), Bornstein, S.R. (Stefan), Brown, M.J. (Morris), Burnier, M. (Michel), Cabrera, C.P. (Claudia P.), Chambers, J.C. (John), Chang, I.-S. (I-Shou), Cheng, C.-Y. (Ching-Yu), Chines, P.S. (Peter), Chung, R.-H. (Ren-Hua), Collins, F.S. (Francis), Connell, J.M. (John M.), Döring, A. (Angela), Dallongeville, J., Danesh, J. (John), Faire, U. (Ulf) de, Delgado, G., Dominiczak, A. (Anna), Doney, A.S.F. (Alex), Drenos, F. (Fotios), Edkins, T. (Ted), Eicher, J.D. (John D.), Elosua, R. (Roberto), Enroth, S. (Stefan), Erdmann, J. (Jeanette), Eriksson, P. (Per), Esko, T. (Tõnu), Evangelou, E. (Evangelos), Evans, A. (Alun), Fall, M. (Magnus), Farrall, M. (Martin), Felix, J.F. (Janine), Ferrieres, J. (Jean), Ferrucci, L. (Luigi), Fornage, M. (Myriam), Forrester, T. (Terrence), Franceschini, N. (Nora), Franco, O.H. (Oscar), Franco-Cereceda, A. (Anders), Fraser, R.M. (Ross), Ganesh, S.K. (Santhi), Gao, H. (He), Gertow, K. (Karl), Gianfagna, F. (Francesco), Gigante, B. (Bruna), Giulianini, F. (Franco), Goel, A. (Anuj), Goodall, A.H. (Alison), Goodarzi, M. (Mark), Gorski, M. (Mathias), Gräßler, J. (Jürgen), Groves, C.J. (Christopher), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hallmans, G. (Göran), Hartikainen, A.L., Hassinen, M. (Maija), Havulinna, A.S. (Aki), Hayward, C. (Caroline), Hercberg, S. (Serge), Herzig, K.H., Hicks, A.A. (Andrew), Hingorani, A. (Aroon), Hirschhorn, J.N. (Joel), Hofman, A. (Albert), Holmen, J. (Jostein), Holmen, O.L. (Oddgeir), Hottenga, J.J. (Jouke Jan), Howard, P. (Philip), Hsiung, C.A. (Chao A.), Hunt, S.C. (Steven), Ikram, M.K. (Kamran), Illig, T. (Thomas), Iribarren, C. (Carlos), Jensen, R.A. (Richard A.), Kähönen, M. (Mika), Kang, H.M. (Hyun Min), Kathiresan, S. (Sekar), Keating, J. (John), Khaw, K.T., Kim, Y.K. (Yun Kyoung), Kim, E. (Eric), Kivimaki, M. (Mika), Klopp, N. (Norman), Kolovou, G. (Genovefa), Komulainen, P. (Pirjo), Kooner, J.S. (Jaspal S.), Kosova, G. (Gulum), Krauss, R.M. (Ronald), Kuh, D. (Diana), Kutalik, Z. (Zoltán), Kuusisto, J. (Johanna), Kvaløy, K. (Kirsti), Lakka, T.A. (Timo), Lee, N.R. (Nanette), Lee, I.T., Lee, W.-J. (Wen-Jane), Levy, D. (Daniel), Li, X. (Xiaohui), Liang, K.-W. (Kae-Woei), Lin, H. (Honghuang), Lin, L. (Li), Lindström, J. (Jaana), Lobbens, S. (Stéphane), Männistö, S. (Satu), Müller, G. (Gabriele), Müller-Nurasyid, M. (Martina), MacH, F. (François), Markus, H.S. (Hugh), Marouli, E. (Eirini), McCarthy, M.I. (Mark), McKenzie, C.A. (Colin), Meneton, P. (Pierre), Menni, C. (Cristina), Metspalu, A. (Andres), Mijatovic, V. (Vladan), Moilanen, L. (Leena), Montasser, M.E. (May E.), Morris, A.D. (Andrew), Morrison, A.C. (Alanna), Mulas, A. (Antonella), Nagaraja, R. (Ramaiah), Narisu, N. (Narisu), Nikus, K. (Kjell), O'Donnell, C.J. (Christopher), O'Reilly, P.F. (Paul), Ong, K.K. (Ken), Paccaud, F. (Fred), Palmer, C. (Cameron), Parsa, A. (Afshin), Pedersen, N.L. (Nancy), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Peters, A. (Annette), Poulter, N.R. (Neil), Pramstaller, P.P. (Peter Paul), Psaty, B.M. (Bruce), Quertermous, T. (Thomas), Rao, D.C. (Dabeeru C.), Rasheed, A. (Asif), Rayner, N.W. (Nigel William), Renström, F. (Frida), Rettig, R. (Rainer), Rice, K.M. (Kenneth), Roberts, R. (Robert), Rose, L.M. (Lynda), Rossouw, J. (Jacques), Samani, N.J. (Nilesh), Sanna, S. (Serena), Saramies, J. (Jouko), Schunkert, H. (Heribert), Sebert, S. (Sylvain), Sheu, W.H.-H. (Wayne H.-H.), Shin, Y.-A. (Young-Ah), Sim, X. (Xueling), Smith, A.V. (Davey), Smith, A.V. (Albert Vernon), Sosa, M.X. (Maria X.), Spector, T.D. (Timothy), Stancáková, A. (Alena), Stanton, A. (Alice), Stirrups, K. (Kathy), Stringham, H.M. (Heather), Sundstrom, J. (Johan), Swift, A.J. (Amy), Syvänen, A.C., Tai, E.-S. (E-Shyong), Tanaka, T. (Toshiko), Tarasov, K.V. (Kirill), Teumer, A. (Alexander), Thorsteinsdottir, U. (Unnur), Tobin, M.D. (Martin), Tremoli, E. (Elena), Uitterlinden, A.G. (Andre G.), Uusitupa, M. (Matti), Vaez, A. (Ahmad), Vaidya, D. (Dhananjay), Van Duijn, C.M. (Cornelia M.), Iperen, E.P.A. (Erik) van, Vasan, R.S. (Ramachandran S.), Verwoert, G.C. (Germaine), Virtamo, J. (Jarmo), Vitart, V. (Veronique), Voight, B.F. (Benjamin), Vollenweider, P. (Peter), Wagner, A. (Aline), Wain, L.V. (Louise V.), Wareham, N.J. (Nick), Watkins, H. (Hugh), Weder, A.B. (Alan), Westra, H.J. (Harm-Jan), Wilks, R. (Rainford), Wilsgaard, T. (Tom), Wilson, J.F. (James F.), Wong, T.Y. (Tien Y.), Yang, T.-P. (Tsun-Po), Yao, J. (Jiefen), Yengo, L. (Loic), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Zhu, X. (Xiaofeng), Bovet, P. (Pascal), Cooper, R.S. (Richard S.), Mohlke, K.L. (Karen), Saleheen, D. (Danish), Lee, J.-Y. (Jong-Young), Elliott, P. (Paul), Gierman, L.M. (Lobke), Willer, C.J. (Cristen), Franke, L. (Lude), Hovingh, G.K. (Kees), Taylor, K.D. (Kent), Dedoussis, G.V. (George), Sever, P. (Peter), Wong, A. (Andrew), Kao, W.H.L. (Wen), Assimes, T.L. (Themistocles), Njølstad, I. (Inger), Schwarz, P.E.H. (Peter), Langenberg, C. (Claudia), Snieder, H. (Harold), Caulfield, M. (Mark), Melander, O. (Olle), Laakso, M. (Markku), Saltevo, J. (Juha), Rauramaa, R. (Rainer), Tuomilehto, J. (Jaakko), Ingelsson, E. (Erik), Lehtimäki, T. (Terho), Hveem, K. (Kristian), Palmas, W. (Walter), März, W. (Winfried), Kumari, M. (Meena), Salomaa, V. (Veikko), Chen, Y.D. (Y.), Rotter, J.I. (Jerome I.), Froguel, P. (Philippe), Jarvelin, M.-R. (Marjo-Riitta), Lakatta, E. (Edward), Kuulasmaa, K. (Kari), Franks, P.W. (Paul), Hamsten, A. (Anders), Wichmann, H.E. (Heinz Erich), Palmer, C.N.A. (Colin), Stefansson, K. (Kari), Ridker, P.M. (Paul), Loos, R.J.F. (Ruth), Chakravarti, A. (Aravinda), Deloukas, P. (Panagiotis), Morris, A.P. (Andrew), Newton-Cheh, C. (C.), Munroe, P. (Patricia), Ehret, G.B. (Georg), Ferreira, T. (Teresa), Chasman, D.I. (Daniel), Jackson, A.U. (Anne), Schmidt, E.M. (Ellen), Johnson, T. (Toby), Thorleifsson, G. (Gudmar), Luan, J. (Jian'An), Donnelly, L.A. (Louise), Kanoni, S. (Stavroula), Petersen, A.K., Pihur, V. (Vasyl), Strawbridge, R.J. (Rona), Shungin, D. (Dmitry), Hughes, M.F. (Maria F.), Meirelles, O., Kaakinen, M. (Marika), Bouatia-Naji, N. (Nabila), Kristiansson, K. (Kati), Shah, S. (Sonia), Kleber, M.E. (Marcus), Guo, X. (Xiuqing), Lyytikäinen, L.-P. (Leo-Pekka), Fava, C. (Cristiano), Eriksson, N. (Niclas), Nolte, I.M. (Ilja), Magnusson, P.K. (Patrik), Salfati, E. (Elias), Rallidis, L.S. (Loukianos), Theusch, E. (Elizabeth), Smith, A.J. (Andrew), Folkersen, L. (Lasse), Witkowska, H.E. (Ewa), Pers, T.H. (Tune), Joehanes, R. (Roby), Kim, S.K. (Stuart K.), Lataniotis, L. (Lazaros), Jansen, R., Johnson, A.D. (Andrew), Warren, H. (Helen), Kim, Y.J., Zhao, W. (Wei), Wu, Y. (Ying), Tayo, B. (Bamidele), Bochud, M. (Murielle), Absher, D. (Devin), Adair, L.S. (Linda), Amin, N. (Najaf), Arking, D.E. (Dan), Axelsson, T. (Tomas), Baldassarre, D. (Damiano), Balkau, B. (Beverley), Bandinelli, S. (Stefania), Barnes, M.J. (Michael), Barroso, I.E. (Inês), Bevan, S. (Stephen), Bis, J.C. (Joshua), Bjornsdottir, G. (Gyda), Boehnke, M. (Michael), Boerwinkle, E.A. (Eric), Bonnycastle, L.L. (Lori), Boomsma, D.I. (Dorret), Bornstein, S.R. (Stefan), Brown, M.J. (Morris), Burnier, M. (Michel), Cabrera, C.P. (Claudia P.), Chambers, J.C. (John), Chang, I.-S. (I-Shou), Cheng, C.-Y. (Ching-Yu), Chines, P.S. (Peter), Chung, R.-H. (Ren-Hua), Collins, F.S. (Francis), Connell, J.M. (John M.), Döring, A. (Angela), Dallongeville, J., Danesh, J. (John), Faire, U. (Ulf) de, Delgado, G., Dominiczak, A. (Anna), Doney, A.S.F. (Alex), Drenos, F. (Fotios), Edkins, T. (Ted), Eicher, J.D. (John D.), Elosua, R. (Roberto), Enroth, S. (Stefan), Erdmann, J. (Jeanette), Eriksson, P. (Per), Esko, T. (Tõnu), Evangelou, E. (Evangelos), Evans, A. (Alun), Fall, M. (Magnus), Farrall, M. (Martin), Felix, J.F. (Janine), Ferrieres, J. (Jean), Ferrucci, L. (Luigi), Fornage, M. (Myriam), Forrester, T. (Terrence), Franceschini, N. (Nora), Franco, O.H. (Oscar), Franco-Cereceda, A. (Anders), Fraser, R.M. (Ross), Ganesh, S.K. (Santhi), Gao, H. (He), Gertow, K. (Karl), Gianfagna, F. (Francesco), Gigante, B. (Bruna), Giulianini, F. (Franco), Goel, A. (Anuj), Goodall, A.H. (Alison), Goodarzi, M. (Mark), Gorski, M. (Mathias), Gräßler, J. (Jürgen), Groves, C.J. (Christopher), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hallmans, G. (Göran), Hartikainen, A.L., Hassinen, M. (Maija), Havulinna, A.S. (Aki), Hayward, C. (Caroline), Hercberg, S. (Serge), Herzig, K.H., Hicks, A.A. (Andrew), Hingorani, A. (Aroon), Hirschhorn, J.N. (Joel), Hofman, A. (Albert), Holmen, J. (Jostein), Holmen, O.L. (Oddgeir), Hottenga, J.J. (Jouke Jan), Howard, P. (Philip), Hsiung, C.A. (Chao A.), Hunt, S.C. (Steven), Ikram, M.K. (Kamran), Illig, T. (Thomas), Iribarren, C. (Carlos), Jensen, R.A. (Richard A.), Kähönen, M. (Mika), Kang, H.M. (Hyun Min), Kathiresan, S. (Sekar), Keating, J. (John), Khaw, K.T., Kim, Y.K. (Yun Kyoung), Kim, E. (Eric), Kivimaki, M. (Mika), Klopp, N. (Norman), Kolovou, G. (Genovefa), Komulainen, P. (Pirjo), Kooner, J.S. (Jaspal S.), Kosova, G. (Gulum), Krauss, R.M. (Ronald), Kuh, D. (Diana), Kutalik, Z. (Zoltán), Kuusisto, J. (Johanna), Kvaløy, K. (Kirsti), Lakka, T.A. (Timo), Lee, N.R. (Nanette), Lee, I.T., Lee, W.-J. (Wen-Jane), Levy, D. (Daniel), Li, X. (Xiaohui), Liang, K.-W. (Kae-Woei), Lin, H. (Honghuang), Lin, L. (Li), Lindström, J. (Jaana), Lobbens, S. (Stéphane), Männistö, S. (Satu), Müller, G. (Gabriele), Müller-Nurasyid, M. (Martina), MacH, F. (François), Markus, H.S. (Hugh), Marouli, E. (Eirini), McCarthy, M.I. (Mark), McKenzie, C.A. (Colin), Meneton, P. (Pierre), Menni, C. (Cristina), Metspalu, A. (Andres), Mijatovic, V. (Vladan), Moilanen, L. (Leena), Montasser, M.E. (May E.), Morris, A.D. (Andrew), Morrison, A.C. (Alanna), Mulas, A. (Antonella), Nagaraja, R. (Ramaiah), Narisu, N. (Narisu), Nikus, K. (Kjell), O'Donnell, C.J. (Christopher), O'Reilly, P.F. (Paul), Ong, K.K. (Ken), Paccaud, F. (Fred), Palmer, C. (Cameron), Parsa, A. (Afshin), Pedersen, N.L. (Nancy), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Peters, A. (Annette), Poulter, N.R. (Neil), Pramstaller, P.P. (Peter Paul), Psaty, B.M. (Bruce), Quertermous, T. (Thomas), Rao, D.C. (Dabeeru C.), Rasheed, A. (Asif), Rayner, N.W. (Nigel William), Renström, F. (Frida), Rettig, R. (Rainer), Rice, K.M. (Kenneth), Roberts, R. (Robert), Rose, L.M. (Lynda), Rossouw, J. (Jacques), Samani, N.J. (Nilesh), Sanna, S. (Serena), Saramies, J. (Jouko), Schunkert, H. (Heribert), Sebert, S. (Sylvain), Sheu, W.H.-H. (Wayne H.-H.), Shin, Y.-A. (Young-Ah), Sim, X. (Xueling), Smith, A.V. (Davey), Smith, A.V. (Albert Vernon), Sosa, M.X. (Maria X.), Spector, T.D. (Timothy), Stancáková, A. (Alena), Stanton, A. (Alice), Stirrups, K. (Kathy), Stringham, H.M. (Heather), Sundstrom, J. (Johan), Swift, A.J. (Amy), Syvänen, A.C., Tai, E.-S. (E-Shyong), Tanaka, T. (Toshiko), Tarasov, K.V. (Kirill), Teumer, A. (Alexander), Thorsteinsdottir, U. (Unnur), Tobin, M.D. (Martin), Tremoli, E. (Elena), Uitterlinden, A.G. (Andre G.), Uusitupa, M. (Matti), Vaez, A. (Ahmad), Vaidya, D. (Dhananjay), Van Duijn, C.M. (Cornelia M.), Iperen, E.P.A. (Erik) van, Vasan, R.S. (Ramachandran S.), Verwoert, G.C. (Germaine), Virtamo, J. (Jarmo), Vitart, V. (Veronique), Voight, B.F. (Benjamin), Vollenweider, P. (Peter), Wagner, A. (Aline), Wain, L.V. (Louise V.), Wareham, N.J. (Nick), Watkins, H. (Hugh), Weder, A.B. (Alan), Westra, H.J. (Harm-Jan), Wilks, R. (Rainford), Wilsgaard, T. (Tom), Wilson, J.F. (James F.), Wong, T.Y. (Tien Y.), Yang, T.-P. (Tsun-Po), Yao, J. (Jiefen), Yengo, L. (Loic), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Zhu, X. (Xiaofeng), Bovet, P. (Pascal), Cooper, R.S. (Richard S.), Mohlke, K.L. (Karen), Saleheen, D. (Danish), Lee, J.-Y. (Jong-Young), Elliott, P. (Paul), Gierman, L.M. (Lobke), Willer, C.J. (Cristen), Franke, L. (Lude), Hovingh, G.K. (Kees), Taylor, K.D. (Kent), Dedoussis, G.V. (George), Sever, P. (Peter), Wong, A. (Andrew), Kao, W.H.L. (Wen), Assimes, T.L. (Themistocles), Njølstad, I. (Inger), Schwarz, P.E.H. (Peter), Langenberg, C. (Claudia), Snieder, H. (Harold), Caulfield, M. (Mark), Melander, O. (Olle), Laakso, M. (Markku), Saltevo, J. (Juha), Rauramaa, R. (Rainer), Tuomilehto, J. (Jaakko), Ingelsson, E. (Erik), Lehtimäki, T. (Terho), Hveem, K. (Kristian), Palmas, W. (Walter), März, W. (Winfried), Kumari, M. (Meena), Salomaa, V. (Veikko), Chen, Y.D. (Y.), Rotter, J.I. (Jerome I.), Froguel, P. (Philippe), Jarvelin, M.-R. (Marjo-Riitta), Lakatta, E. (Edward), Kuulasmaa, K. (Kari), Franks, P.W. (Paul), Hamsten, A. (Anders), Wichmann, H.E. (Heinz Erich), Palmer, C.N.A. (Colin), Stefansson, K. (Kari), Ridker, P.M. (Paul), Loos, R.J.F. (Ruth), Chakravarti, A. (Aravinda), Deloukas, P. (Panagiotis), Morris, A.P. (Andrew), Newton-Cheh, C. (C.), and Munroe, P. (Patricia)
- Abstract
To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.
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- 2016
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9. Investigating the Causal Relationship of C-Reactive Protein with 32 Complex Somatic and Psychiatric Outcomes: A Large-Scale Cross-Consortium Mendelian Randomization Study
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Prins, B.P. (Bram. P.), Abbasi, A. (Ali), Wong, A. (Anson), Vaez, A. (Ahmad), Nolte, I.M. (Ilja), Franceschini, N. (Nora), Stuart, P.E. (Philip E.), Guterriez Achury, J. (Javier), Mistry, V. (Vanisha), Bradfield, J.P. (Jonathan), Valdes, A.M. (Ana Maria), Bras, J. (Jose), Shatunov, A. (Aleksey), Lu, C. (Chao), Han, B. (Buhm), Raychaudhuri, S. (Soumya), Bevan, S. (Steve), Mayes, M.D. (Maureen D.), Tsoi, L.C. (Lam C.), Evangelou, E. (Evangelos), Nair, R.P. (Rajan P.), Grant, S.F.A. (Struan), Polychronakos, C. (Constantin), Radstake, T.R.D.J. (Timothy), Heel, D.A. (David) van, Dunstan, M.L., Wood, N.W. (Nicholas), Al-Chalabi, A. (Ammar), Dehghan, A. (Abbas), Hakonarson, H. (Hakon), Markus, H.S. (Hugh S.), Elder, J.T. (James), Knight, J. (Jo), Arking, D.E. (Dan), Spector, T.D. (Timothy), Koeleman, B.P.C. (Bobby), Duijn, C.M. (Cornelia) van, Martín, J. (Javier), Morris, A.P. (Andrew), Weersma, R.K. (Rinse K.), Wijmenga, C. (Cisca), Munroe, P. (Patricia), Perry, J.R.B. (John), Pouget, J.G. (Jennie G.), Jamshidi, Y. (Yalda), Snieder, H. (Harold), Alizadeh, B.Z. (Behrooz), Prins, B.P. (Bram. P.), Abbasi, A. (Ali), Wong, A. (Anson), Vaez, A. (Ahmad), Nolte, I.M. (Ilja), Franceschini, N. (Nora), Stuart, P.E. (Philip E.), Guterriez Achury, J. (Javier), Mistry, V. (Vanisha), Bradfield, J.P. (Jonathan), Valdes, A.M. (Ana Maria), Bras, J. (Jose), Shatunov, A. (Aleksey), Lu, C. (Chao), Han, B. (Buhm), Raychaudhuri, S. (Soumya), Bevan, S. (Steve), Mayes, M.D. (Maureen D.), Tsoi, L.C. (Lam C.), Evangelou, E. (Evangelos), Nair, R.P. (Rajan P.), Grant, S.F.A. (Struan), Polychronakos, C. (Constantin), Radstake, T.R.D.J. (Timothy), Heel, D.A. (David) van, Dunstan, M.L., Wood, N.W. (Nicholas), Al-Chalabi, A. (Ammar), Dehghan, A. (Abbas), Hakonarson, H. (Hakon), Markus, H.S. (Hugh S.), Elder, J.T. (James), Knight, J. (Jo), Arking, D.E. (Dan), Spector, T.D. (Timothy), Koeleman, B.P.C. (Bobby), Duijn, C.M. (Cornelia) van, Martín, J. (Javier), Morris, A.P. (Andrew), Weersma, R.K. (Rinse K.), Wijmenga, C. (Cisca), Munroe, P. (Patricia), Perry, J.R.B. (John), Pouget, J.G. (Jennie G.), Jamshidi, Y. (Yalda), Snieder, H. (Harold), and Alizadeh, B.Z. (Behrooz)
- Abstract
Background: C-reactive protein (CRP) is associated with immune, cardiometabolic, and psychiatric traits and diseases. Yet it is inconclusive whether these associations are causal. Methods and Findings: We performed Mendelian randomization (MR) analyses using two genetic risk scores (GRSs) as instrumental variables (IVs). The first GRS consisted of four single nucleotide polymorphisms (SNPs) in the CRP gene (GRSCRP), and the second consisted of 18 SNPs that were significantly associated with CRP levels in the largest genome-wide association study (GWAS) to date (GRSGWAS). To optimize power, we used summ
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- 2016
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10. Bivariate genome-wide association study identifies novel pleiotropic loci for lipids and inflammation
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Ligthart, S. (Symen), Vaez, A. (Ahmad), Hsu, Y.-H. (Yi-Hsiang), Stolk, R.P. (Ronald), Uitterlinden, A.G. (André), Hofman, A. (Albert), Alizadeh, B.Z. (Behrooz), Franco, O.H. (Oscar), Dehghan, A. (Abbas), Ligthart, S. (Symen), Vaez, A. (Ahmad), Hsu, Y.-H. (Yi-Hsiang), Stolk, R.P. (Ronald), Uitterlinden, A.G. (André), Hofman, A. (Albert), Alizadeh, B.Z. (Behrooz), Franco, O.H. (Oscar), and Dehghan, A. (Abbas)
- Abstract
Background: Genome-wide association studies (GWAS) have identified multiple genetic loci for C-reactive protein (CRP) and lipids, of which some overlap. We aimed to identify genetic pleiotropy among CRP and lipids in order to better understand the shared biology of chronic inflammation and lipid metabolism. Results: In a bivariate GWAS, we combined summary statistics of published GWAS on CRP (n = 66,185) and lipids, including LDL-cholesterol, HDL-cholesterol, triglycerides, and total cholesterol (n = 100,184), using an empirical weighted linear-combined test statistic. We sought replication for novel CRP associations in an independent sample of 17,743 genotyped individuals, and performed in silico replication of novel lipid variants in 93,982 individuals. Fifty potentially pleiotropic SNPs were identified among CRP and lipids: 21 for LDL-cholesterol and CRP, 20 for HDL-cholesterol and CRP, 21 for triglycerides, and CRP and 20 for total cholesterol and CRP. We identified and significantly replicated three novel SNPs for CRP in or near CTSB/FDFT1 (rs10435719, Preplication: 2.6 × 10-5), STAG1/PCCB (rs7621025, Preplication: 1.4 × 10-3) and FTO (rs1558902, Preplication: 2.7 × 10-5). Seven pleiotropic lipid loci were replicated in the independent set of MetaboChip samples of the Global Lipids Genetics Consortium. Annotating the effect of replicated CRP SNPs to the expression of nearby genes, we observed an effect of rs10435719 on gene expression of FDFT1, and an effect of rs7621025 on PCCB. Conclusions: Our large scale combined GWAS analysis identified numerous pleiotropic loci for CRP and lipids providing further insight in the genetic interrelation between lipids and inflammation. In addition, we provide evidence for FDFT1, PCCB and FTO to be associated with CRP levels.
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- 2016
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11. DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide Consortium Meta-analysis
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Joubert, B.R. (Bonnie), Felix, J.F. (Janine), Yousefi, P. (Paul), Bakulski, K.M. (Kelly M.), Just, A.C. (Allan C.), Breton, C. (Carrie), Reese, S.E. (Sarah E.), Markunas, C.A. (Christina A.), Richmond, R.C. (Rebecca C.), Xu, C.-J. (Cheng-Jian), Küpers, L.K. (Leanne), Oh, S.S. (Sam S.), Hoyo, C. (Cathrine), Gruzieva, O. (Olena), Söderhäll, C. (Cilla), Salas, L.A. (Lucas A.), Baïz, N. (Nour), Zhang, H. (Hongmei), Lepeule, J. (Johanna), Ruiz, C. (Carlos), Ligthart, S. (Symen), Wang, T. (Tianyuan), Taylor, J.A. (Jack A.), Duijts, L. (Liesbeth), Sharp, G.C. (Gemma C.), Jankipersadsing, S.A. (Soesma A.), Nilsen, R.M. (Roy M.), Vaez, A. (Ahmad), Fallin, M.D. (M. Daniele), Hu, D. (Donglei), Litonjua, A.A. (Augusto), Fuemmeler, B.F. (Bernard F.), Huen, K. (Karen), Kere, J. (Juha), Kull, C.A. (Christian), Munthe-Kaas, M.C. (Monica Cheng), Gehring, U. (Ulrike), Bustamante, M. (Mariona), Saurel-Coubizolles, M.J. (Marie José), Quraishi, B.M. (Bilal M.), Ren, J. (Jie), Tost, J. (Jörg), Gonzalez, J.R. (Juan R.), Peters, M.J. (Marjolein), Håberg, S.E. (Siri E), Xu, Z. (Zongli), Meurs, J.B.J. (Joyce) van, Gaunt, T.R. (Tom), Kerkhof, M. (Marjan), Corpeleijn, W.E. (Willemijn), Feinberg, A.P. (Andrew P.), Eng, C. (Celeste), Baccarelli, A.A. (Andrea), Benjamin Neelon, S.E. (Sara E.), Bradman, A. (Asa), Merid, S.K. (Simon Kebede), Bergström, A. (Anna), Herceg, Z. (Zdenko), Hernandez-Vargas, H. (Hector), Brunekreef, B. (Bert), Pinart, M. (Mariona), Heude, B. (Barbara), Ewart, S. (Susan), Yao, J. (Jin), Lemonnier, N. (Nathanaël), Franco, O.H. (Oscar), Wu, M.C. (Michael), Hofman, A. (Albert), McArdle, W.L. (Wendy), Vlies, P. (P.) van der, Falahi, F. (Fahimeh), Gillman, M.W. (Matthew W.), Barcellos, L.F. (Lisa), Kumar, A. (Ashish), Wickman, M. (Magnus), Guerra, S. (S.), Charles, M.-A. (Marie-Aline), Holloway, J. (John), Auffray, C. (C.), Tiemeier, H.W. (Henning), Smith, A.V. (Davey), Postma, D.S. (Dirkje), Hivert, M.-F. (Marie-France), Eskenazi, B. (Brenda), Vrijheid, M. (Martine), Arshad, H. (Hasan), Anto, J.M. (Josep), Dehghan, A. (Abbas), Karmaus, W. (Wilfried), Annesi-Maesano, I. (Isabella), Sunyer, J. (Jordi), Ghantous, A. (Akram), Pershagen, G. (Göran), Holland, N. (Nina), Murphy, S.K. (Susan K.), Demeo, D.L. (Dawn), Burchard, E.G. (Esteban), Ladd-Acosta, C. (Christine), Snieder, H. (Harold), Nystad, W. (Wenche), Koppelman, G.H. (Gerard), Relton, C.L. (Caroline), Jaddoe, V.W.V. (Vincent), Wilcox, A.J. (Allen), Melén, E. (Erik), London, S.J. (Stephanie J.), Joubert, B.R. (Bonnie), Felix, J.F. (Janine), Yousefi, P. (Paul), Bakulski, K.M. (Kelly M.), Just, A.C. (Allan C.), Breton, C. (Carrie), Reese, S.E. (Sarah E.), Markunas, C.A. (Christina A.), Richmond, R.C. (Rebecca C.), Xu, C.-J. (Cheng-Jian), Küpers, L.K. (Leanne), Oh, S.S. (Sam S.), Hoyo, C. (Cathrine), Gruzieva, O. (Olena), Söderhäll, C. (Cilla), Salas, L.A. (Lucas A.), Baïz, N. (Nour), Zhang, H. (Hongmei), Lepeule, J. (Johanna), Ruiz, C. (Carlos), Ligthart, S. (Symen), Wang, T. (Tianyuan), Taylor, J.A. (Jack A.), Duijts, L. (Liesbeth), Sharp, G.C. (Gemma C.), Jankipersadsing, S.A. (Soesma A.), Nilsen, R.M. (Roy M.), Vaez, A. (Ahmad), Fallin, M.D. (M. Daniele), Hu, D. (Donglei), Litonjua, A.A. (Augusto), Fuemmeler, B.F. (Bernard F.), Huen, K. (Karen), Kere, J. (Juha), Kull, C.A. (Christian), Munthe-Kaas, M.C. (Monica Cheng), Gehring, U. (Ulrike), Bustamante, M. (Mariona), Saurel-Coubizolles, M.J. (Marie José), Quraishi, B.M. (Bilal M.), Ren, J. (Jie), Tost, J. (Jörg), Gonzalez, J.R. (Juan R.), Peters, M.J. (Marjolein), Håberg, S.E. (Siri E), Xu, Z. (Zongli), Meurs, J.B.J. (Joyce) van, Gaunt, T.R. (Tom), Kerkhof, M. (Marjan), Corpeleijn, W.E. (Willemijn), Feinberg, A.P. (Andrew P.), Eng, C. (Celeste), Baccarelli, A.A. (Andrea), Benjamin Neelon, S.E. (Sara E.), Bradman, A. (Asa), Merid, S.K. (Simon Kebede), Bergström, A. (Anna), Herceg, Z. (Zdenko), Hernandez-Vargas, H. (Hector), Brunekreef, B. (Bert), Pinart, M. (Mariona), Heude, B. (Barbara), Ewart, S. (Susan), Yao, J. (Jin), Lemonnier, N. (Nathanaël), Franco, O.H. (Oscar), Wu, M.C. (Michael), Hofman, A. (Albert), McArdle, W.L. (Wendy), Vlies, P. (P.) van der, Falahi, F. (Fahimeh), Gillman, M.W. (Matthew W.), Barcellos, L.F. (Lisa), Kumar, A. (Ashish), Wickman, M. (Magnus), Guerra, S. (S.), Charles, M.-A. (Marie-Aline), Holloway, J. (John), Auffray, C. (C.), Tiemeier, H.W. (Henning), Smith, A.V. (Davey), Postma, D.S. (Dirkje), Hivert, M.-F. (Marie-France), Eskenazi, B. (Brenda), Vrijheid, M. (Martine), Arshad, H. (Hasan), Anto, J.M. (Josep), Dehghan, A. (Abbas), Karmaus, W. (Wilfried), Annesi-Maesano, I. (Isabella), Sunyer, J. (Jordi), Ghantous, A. (Akram), Pershagen, G. (Göran), Holland, N. (Nina), Murphy, S.K. (Susan K.), Demeo, D.L. (Dawn), Burchard, E.G. (Esteban), Ladd-Acosta, C. (Christine), Snieder, H. (Harold), Nystad, W. (Wenche), Koppelman, G.H. (Gerard), Relton, C.L. (Caroline), Jaddoe, V.W.V. (Vincent), Wilcox, A.J. (Allen), Melén, E. (Erik), and London, S.J. (Stephanie J.)
- Abstract
Epigenetic modifications, including DNA methylation, represent a potential mechanism for environmental impacts on human disease. Maternal smoking in pregnancy remains an important public health problem that impacts child health in a myriad of ways and has potential lifelong consequences. The mechanisms are largely unknown, but epigenetics most likely plays a role. We formed the Pregnancy And Childhood Epigenetics (PACE) consortium and meta-analyzed, across 13 cohorts (n = 6,685), the association between maternal smoking in pregnancy and newborn blood DNA methylation at over 450,000 CpG sites (CpGs) by using the Illumina 450K BeadChip. Over 6,000 CpGs were differentially methylated in relation to maternal smoking at genome-wide statistical significance (false discovery rate, 5%), including 2,965 CpGs corresponding to 2,017 genes not previously related to smoking and methylation in either newborns or adults. Several genes are relevant to diseases that can be caused by maternal smoking (e.g., orofacial clefts and asthma) or adult smoking (e.g., certain cancers). A number of differentially methylated CpGs were associated with gene expression. We observed enrichment in pathwa
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- 2016
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12. The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals
- Author
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Ehret, G. B. (Georg B.), Ferreira, T. (Teresa), Chasman, D. I. (Daniel I.), Jackson, A. U. (Anne U.), Schmidt, E. M. (Ellen M.), Johnson, T. (Toby), Thorleifsson, G. (Gudmar), Luan, J. (Jian'an), Donnelly, L. A. (Louise A.), Kanoni, S. (Stavroula), Petersen, A. -. (Ann -Kristin), Pihurl, V. (Vasyl), Strawbridge, R. J. (Rona J.), Shungin, D. (Dmitry), Hughes, M. F. (Maria F.), Meirelles, O. (Osorio), Kaakinen, M. (Marika), Bouatia-Naji, N. (Nabila), Kristiansson, K. (Kati), Shah, S. (Sonia), Kleber, M. E. (Marcus E.), Guo, X. (Xiuqing), Lyytikainen, L.-P. (Leo-Pekka), Fava, C. (Cristiano), Eriksson, N. (Nidas), Nolte, I. M. (Ilja M.), Magnusson, P. K. (Patrik K.), Salfati, E. L. (Elias L.), Rallidis, L. S. (Loukianos S.), Theusch, E. (Elizabeth), Smith, A. J. (Andrew J. P.), Folkersen, L. (Lasse), Witkowska, K. (Kate), Pers, T. H. (Tune H.), Joehanes, R. (Roby), Kim, S. K. (Stuart K.), Lataniotis, L. (Lazaros), Jansen, R. (Rick), Johnson, A. D. (Andrew D.), Warren, H. (Helen), Kim, Y. J. (Young Jin), Zhao, W. (Wei), Wu, Y. (Ying), Tayo, B. O. (Bamidele O.), Bochud, M. (Murielle), Absher, D. (Devin), Adair, L. S. (Linda S.), Amin, N. (Najaf), Arkingl, D. E. (Dan E.), Axelsson, T. (Tomas), Baldassarre, D. (Damian), Balkau, B. (Beverley), Bandinelli, S. (Stefania), Barnes, M. R. (Michael R.), Barroso, I. (Ines), Bevan, S. (Stephen), Bis, J. C. (Joshua C.), Bjornsdottir, G. (Gyda), Boehnke, M. (Michael), Boerwinkle, E. (Eric), Bonnycastle, L. L. (Lori L.), Boomsma, D. I. (Dorret I.), Bornstein, S. R. (Stefan R.), Brown, M. J. (Morris J.), Burnier, M. (Michel), Cabrera, C. P. (Claudia P.), Chambers, J. C. (John C.), Chang, I.-S. (I-Shou), Cheng, C.-Y. (Ching-Yu), Chines, P. S. (Peter S.), Chung, R.-H. (Ren-Hua), Collins, F. S. (Francis S.), Connell, J. M. (John M.), Doring, A. (Angela), Dallongeville, J. (Jean), Danesh, J. (John), de Faire, U. (Ulf), Delgado, G. (Graciela), Dominiczak, A. F. (Anna F.), Doney, A. S. (Alex S. F.), Drenos, F. (Fotios), Edkins, S. (Sarah), Eicher, J. D. (John D.), Elosua, R. (Roberto), Enroth, S. (Stefan), Erdmann, J. (Jeanette), Eriksson, P. (Per), Esko, T. (Tonu), Evangelou, E. (Evangelos), Evans, A. (Alun), Fai, T. (Tove), Farra, M. (Martin), Felixl, J. F. (Janine F.), Ferrieres, J. (Jean), Ferrucci, L. (Luigi), Fornage, M. (Myriam), Forrester, T. (Terrence), Franceschinil, N. (Nora), Franco, O. H. (Oscar H.), Franco-Cereceda, A. (Anders), Fraser, R. M. (Ross M.), Ganesh, S. K. (Santhi K.), Gao, H. (He), Gertow, K. (Karl), Gianfagna, F. (Francesco), Gigante, B. (Bruna), Giulianini, F. (Franco), Goe, A. (Anuj), Goodall, A. H. (Alison H.), Goodarzi, M. (Mark), Gorski, M. (Mathias), Grassler, J. (Jurgen), Groves, C. J. (Christopher J.), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hallmans, G. (Goran), Hartikainen, A.-L. (Anna-Liisa), Hassinen, M. (Maija), Havulinna, A. S. (Aki S.), Hayward, C. (Caroline), Hercberg, S. (Serge), Herzig, K.-H. (Karl-Heinz), Hicks, A. A. (Andrew A.), Hingorani, A. D. (Aroon D.), Hirschhorn, J. N. (Joel N.), Hofmanl, A. (Albert), Holmen, J. (Jostein), Holmen, O. L. (Oddgeir Lingaas), Hottenga, J.-J. (Jouke-Jan), Howard, P. (Phil), Hsiung, C. A. (Chao A.), Hunt, S. C. (Steven C.), Ikram, M. A. (M. Arfan), Illig, T. (Thomas), Iribarren, C. (Carlos), Jensen, R. A. (Richard A.), Kahonen, M. (Mika), Kang, H. M. (Hyun Min), Kathiresan, S. (Sekar), Keating, B. J. (Brendan J.), Khaw, K.-T. (Kay-Tee), Kim, Y. K. (Yun Kyoung), Kim, E. (Eric), Kivimaki, M. (Mika), Klopp, N. (Norman), Kolovou, G. (Genovefa), Komulainen, P. (Pirjo), Kooner, J. S. (Jaspal S.), Kosova, G. (Gulum), Krauss, R. M. (Ronald M.), Kuh, D. (Diana), Kutalik, Z. (Zoltan), Kuusisto, J. (Johanna), Kvaloy, K. (Kirsti), Lakka, T. A. (Timo A.), Lee, N. R. (Nanette R.), Lee, I.-T. (I-Te), Lee, W.-J. (Wen-Jane), Levy, D. (Daniel), Li, X. (Xiaohui), Liang, K.-W. (Kae-Woei), Lin, H. (Honghuang), Lin, L. (Li), Lindstrom, J. (Jaana), Lobbens, S. (Stephane), Mannisto, S. (Satu), Muller, G. (Gabriele), Muller-Nurasyid, M. (Martina), Mach, F. (Francois), Markus, H. S. (Hugh S.), Marouli, E. (Eirini), McCarthy, M. I. (Mark I.), McKenzie, C. A. (Colin A.), Meneton, P. (Pierre), Menni, C. (Cristina), Metspalu, A. (Andres), Mijatovic, V. (Vladan), Moilanen, L. (Leena), Montasser, M. E. (May E.), Morris, A. D. (Andrew D.), Morrison, A. C. (Alanna C.), Mulas, A. (Antonella), Nagaraja, R. (Ramaiah), Narisu, N. (Narisu), Nikus, K. (Kjell), O'Donnell, C. J. (Christopher J.), O'Reilly, P. F. (Paul F.), Ong, K. K. (Ken K.), Paccaud, F. (Fred), Palmer, C. D. (Cameron D.), Parsa, A. (Afshin), Pedersen, N. L. (Nancy L.), Penninx, B. W. (Brenda W.), Perola, M. (Markus), Peters, A. (Annette), Poulter, N. (Neil), Pramstaller, P. P. (Peter P.), Psaty, B. M. (Bruce M.), Quertermous, T. (Thomas), Rao, D. C. (Dabeeru C.), Rasheed, A. (Asif), Rayner, N. W. (N. William), Renstrom, F. (Frida), Rettig, R. (Rainer), Rice, K. M. (Kenneth M.), Roberts, R. (Robert), Rose, L. M. (Lynda M.), Rossouw, J. (Jacques), Samani, N. J. (Nilesh J.), Sanna, S. (Serena), Saramies, J. (Jouko), Schunkert, H. (Heribert), Sebert, S. (Sylvain), Sheu, W. H. (Wayne H-H), Shin, Y.-A. (Young-Ah), Sim, X. (Xueling), Smit, J. H. (Johannes H.), Smith, A. V. (Albert V.), Sosa, M. X. (Maria X.), Spector, T. D. (Tim D.), Stancakova, A. (Alena), Stanton, A. V. (Alice V.), Stirrups, K. E. (Kathleen E.), Stringham, H. M. (Heather M.), Sundstrom, J. (Johan), Swift, A. J. (Amy J.), Syvanen, A.-C. (Ann-Christine), Tai, E.-S. (E-Shyong), Tanaka, T. (Toshiko), Tarasov, K. V. (Kirill V.), Teumer, A. (Alexander), Thorsteinsdottir, U. (Unnur), Tobin, M. D. (Martin D.), Tremoli, E. (Elena), Uitterlinden, A. G. (Andre G.), Uusitupa, M. (Matti), Vaez, A. (Ahmad), Vaidya, D. (Dhananjay), van Duijn, C. M. (Cornelia M.), van Iperen, E. P. (Erik P. A.), Vasan, R. S. (Ramachandran S.), Verwoert, G. C. (Germaine C.), Virtamo, J. (Jarmo), Vitart, V. (Veronique), Voight, B. F. (Benjamin F.), Vollenweider, P. (Peter), Wagner, A. (Aline), Wain, L. V. (Louise V.), Wareham, N. J. (Nicholas J.), Watldns, H. (Hugh), Weder, A. B. (Alan B.), Westra, H. J. (Harm Jan), Wilks, R. (Rainford), Wilsgaard, T. (Tom), Wilson, J. F. (James F.), Wong, T. Y. (Tien Y.), Yang, T.-P. (Tsun-Po), Yao, J. (Jie), Yengo, L. (Loic), Zhang, W. (Weihua), Zhao, J. H. (Jing Hua), Zhu, X. (Xiaofeng), Bovet, P. (Pascal), Cooper, R. S. (Richard S.), Mohlke, K. L. (Karen L.), Saleheen, D. (Danish), Lee, J.-Y. (Jong-Young), Elliott, P. (Paul), Gierman, H. J. (Hinco J.), Willer, C. J. (Cristen J.), Franke, L. (Lude), Hovingh, G. K. (G. Kees), Taylor, K. D. (Kent D.), Dedoussis, G. (George), Sever, P. (Peter), Wong, A. (Andrew), Lind, L. (Lars), Assimes, T. L. (Themistocles L.), Njolstad, I. (Inger), Schwarz, P. E. (Peter E. H.), Langenberg, C. (Claudia), Snieder, H. (Harold), Caulfield, M. J. (Mark J.), Melander, E. (E.), Laakso, M. (Markku), Saltevo, J. (Juha), Rauramaa, R. (Rainer), Tuomilehto, J. (Jaakko), Ingelsson, E. (Erik), Lehtimaki, T. (Terho), Hveem, K. (Kristian), Palmas, W. (Walter), Marz, W. (Winfried), Kumar, M. (Meena), Salomaa, V. (Veikko), Chen, Y. I. (Yii-Der I.), Rotter, J. I. (Jerome I.), Froguel, P. (Philippe), Jarvelin, M.-R. (Marjo-Riitta), Lakatta, E. G. (Edward G.), Kuulasmaa, K. (Kari), Franks, P. W. (Paul W.), Hamsten, A. (Anders), Wichmann, H.-E. (H-Erich), Palmer, C. N. (Colin N. A.), Stefansson, K. (Kari), Ridker, P. M. (Paul M.), Loos, R. J. (Ruth J. F.), Chalcravarti, A. (Aravinda), Deloukas, P. (Panos), Morris, A. P. (Andrew P.), Newton-Cheh, C. (Christopher), Munroe, P. B. (Patricia B.), Ehret, G. B. (Georg B.), Ferreira, T. (Teresa), Chasman, D. I. (Daniel I.), Jackson, A. U. (Anne U.), Schmidt, E. M. (Ellen M.), Johnson, T. (Toby), Thorleifsson, G. (Gudmar), Luan, J. (Jian'an), Donnelly, L. A. (Louise A.), Kanoni, S. (Stavroula), Petersen, A. -. (Ann -Kristin), Pihurl, V. (Vasyl), Strawbridge, R. J. (Rona J.), Shungin, D. (Dmitry), Hughes, M. F. (Maria F.), Meirelles, O. (Osorio), Kaakinen, M. (Marika), Bouatia-Naji, N. (Nabila), Kristiansson, K. (Kati), Shah, S. (Sonia), Kleber, M. E. (Marcus E.), Guo, X. (Xiuqing), Lyytikainen, L.-P. (Leo-Pekka), Fava, C. (Cristiano), Eriksson, N. (Nidas), Nolte, I. M. (Ilja M.), Magnusson, P. K. (Patrik K.), Salfati, E. L. (Elias L.), Rallidis, L. S. (Loukianos S.), Theusch, E. (Elizabeth), Smith, A. J. (Andrew J. P.), Folkersen, L. (Lasse), Witkowska, K. (Kate), Pers, T. H. (Tune H.), Joehanes, R. (Roby), Kim, S. K. (Stuart K.), Lataniotis, L. (Lazaros), Jansen, R. (Rick), Johnson, A. D. (Andrew D.), Warren, H. (Helen), Kim, Y. J. (Young Jin), Zhao, W. (Wei), Wu, Y. (Ying), Tayo, B. O. (Bamidele O.), Bochud, M. (Murielle), Absher, D. (Devin), Adair, L. S. (Linda S.), Amin, N. (Najaf), Arkingl, D. E. (Dan E.), Axelsson, T. (Tomas), Baldassarre, D. (Damian), Balkau, B. (Beverley), Bandinelli, S. (Stefania), Barnes, M. R. (Michael R.), Barroso, I. (Ines), Bevan, S. (Stephen), Bis, J. C. (Joshua C.), Bjornsdottir, G. (Gyda), Boehnke, M. (Michael), Boerwinkle, E. (Eric), Bonnycastle, L. L. (Lori L.), Boomsma, D. I. (Dorret I.), Bornstein, S. R. (Stefan R.), Brown, M. J. (Morris J.), Burnier, M. (Michel), Cabrera, C. P. (Claudia P.), Chambers, J. C. (John C.), Chang, I.-S. (I-Shou), Cheng, C.-Y. (Ching-Yu), Chines, P. S. (Peter S.), Chung, R.-H. (Ren-Hua), Collins, F. S. (Francis S.), Connell, J. M. (John M.), Doring, A. (Angela), Dallongeville, J. (Jean), Danesh, J. (John), de Faire, U. (Ulf), Delgado, G. (Graciela), Dominiczak, A. F. (Anna F.), Doney, A. S. (Alex S. F.), Drenos, F. (Fotios), Edkins, S. (Sarah), Eicher, J. D. (John D.), Elosua, R. (Roberto), Enroth, S. (Stefan), Erdmann, J. (Jeanette), Eriksson, P. (Per), Esko, T. (Tonu), Evangelou, E. (Evangelos), Evans, A. (Alun), Fai, T. (Tove), Farra, M. (Martin), Felixl, J. F. (Janine F.), Ferrieres, J. (Jean), Ferrucci, L. (Luigi), Fornage, M. (Myriam), Forrester, T. (Terrence), Franceschinil, N. (Nora), Franco, O. H. (Oscar H.), Franco-Cereceda, A. (Anders), Fraser, R. M. (Ross M.), Ganesh, S. K. (Santhi K.), Gao, H. (He), Gertow, K. (Karl), Gianfagna, F. (Francesco), Gigante, B. (Bruna), Giulianini, F. (Franco), Goe, A. (Anuj), Goodall, A. H. (Alison H.), Goodarzi, M. (Mark), Gorski, M. (Mathias), Grassler, J. (Jurgen), Groves, C. J. (Christopher J.), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hallmans, G. (Goran), Hartikainen, A.-L. (Anna-Liisa), Hassinen, M. (Maija), Havulinna, A. S. (Aki S.), Hayward, C. (Caroline), Hercberg, S. (Serge), Herzig, K.-H. (Karl-Heinz), Hicks, A. A. (Andrew A.), Hingorani, A. D. (Aroon D.), Hirschhorn, J. N. (Joel N.), Hofmanl, A. (Albert), Holmen, J. (Jostein), Holmen, O. L. (Oddgeir Lingaas), Hottenga, J.-J. (Jouke-Jan), Howard, P. (Phil), Hsiung, C. A. (Chao A.), Hunt, S. C. (Steven C.), Ikram, M. A. (M. Arfan), Illig, T. (Thomas), Iribarren, C. (Carlos), Jensen, R. A. (Richard A.), Kahonen, M. (Mika), Kang, H. M. (Hyun Min), Kathiresan, S. (Sekar), Keating, B. J. (Brendan J.), Khaw, K.-T. (Kay-Tee), Kim, Y. K. (Yun Kyoung), Kim, E. (Eric), Kivimaki, M. (Mika), Klopp, N. (Norman), Kolovou, G. (Genovefa), Komulainen, P. (Pirjo), Kooner, J. S. (Jaspal S.), Kosova, G. (Gulum), Krauss, R. M. (Ronald M.), Kuh, D. (Diana), Kutalik, Z. (Zoltan), Kuusisto, J. (Johanna), Kvaloy, K. (Kirsti), Lakka, T. A. (Timo A.), Lee, N. R. (Nanette R.), Lee, I.-T. (I-Te), Lee, W.-J. (Wen-Jane), Levy, D. (Daniel), Li, X. (Xiaohui), Liang, K.-W. (Kae-Woei), Lin, H. (Honghuang), Lin, L. (Li), Lindstrom, J. (Jaana), Lobbens, S. (Stephane), Mannisto, S. (Satu), Muller, G. (Gabriele), Muller-Nurasyid, M. (Martina), Mach, F. (Francois), Markus, H. S. (Hugh S.), Marouli, E. (Eirini), McCarthy, M. I. (Mark I.), McKenzie, C. A. (Colin A.), Meneton, P. (Pierre), Menni, C. (Cristina), Metspalu, A. (Andres), Mijatovic, V. (Vladan), Moilanen, L. (Leena), Montasser, M. E. (May E.), Morris, A. D. (Andrew D.), Morrison, A. C. (Alanna C.), Mulas, A. (Antonella), Nagaraja, R. (Ramaiah), Narisu, N. (Narisu), Nikus, K. (Kjell), O'Donnell, C. J. (Christopher J.), O'Reilly, P. F. (Paul F.), Ong, K. K. (Ken K.), Paccaud, F. (Fred), Palmer, C. D. (Cameron D.), Parsa, A. (Afshin), Pedersen, N. L. (Nancy L.), Penninx, B. W. (Brenda W.), Perola, M. (Markus), Peters, A. (Annette), Poulter, N. (Neil), Pramstaller, P. P. (Peter P.), Psaty, B. M. (Bruce M.), Quertermous, T. (Thomas), Rao, D. C. (Dabeeru C.), Rasheed, A. (Asif), Rayner, N. W. (N. William), Renstrom, F. (Frida), Rettig, R. (Rainer), Rice, K. M. (Kenneth M.), Roberts, R. (Robert), Rose, L. M. (Lynda M.), Rossouw, J. (Jacques), Samani, N. J. (Nilesh J.), Sanna, S. (Serena), Saramies, J. (Jouko), Schunkert, H. (Heribert), Sebert, S. (Sylvain), Sheu, W. H. (Wayne H-H), Shin, Y.-A. (Young-Ah), Sim, X. (Xueling), Smit, J. H. (Johannes H.), Smith, A. V. (Albert V.), Sosa, M. X. (Maria X.), Spector, T. D. (Tim D.), Stancakova, A. (Alena), Stanton, A. V. (Alice V.), Stirrups, K. E. (Kathleen E.), Stringham, H. M. (Heather M.), Sundstrom, J. (Johan), Swift, A. J. (Amy J.), Syvanen, A.-C. (Ann-Christine), Tai, E.-S. (E-Shyong), Tanaka, T. (Toshiko), Tarasov, K. V. (Kirill V.), Teumer, A. (Alexander), Thorsteinsdottir, U. (Unnur), Tobin, M. D. (Martin D.), Tremoli, E. (Elena), Uitterlinden, A. G. (Andre G.), Uusitupa, M. (Matti), Vaez, A. (Ahmad), Vaidya, D. (Dhananjay), van Duijn, C. M. (Cornelia M.), van Iperen, E. P. (Erik P. A.), Vasan, R. S. (Ramachandran S.), Verwoert, G. C. (Germaine C.), Virtamo, J. (Jarmo), Vitart, V. (Veronique), Voight, B. F. (Benjamin F.), Vollenweider, P. (Peter), Wagner, A. (Aline), Wain, L. V. (Louise V.), Wareham, N. J. (Nicholas J.), Watldns, H. (Hugh), Weder, A. B. (Alan B.), Westra, H. J. (Harm Jan), Wilks, R. (Rainford), Wilsgaard, T. (Tom), Wilson, J. F. (James F.), Wong, T. Y. (Tien Y.), Yang, T.-P. (Tsun-Po), Yao, J. (Jie), Yengo, L. (Loic), Zhang, W. (Weihua), Zhao, J. H. (Jing Hua), Zhu, X. (Xiaofeng), Bovet, P. (Pascal), Cooper, R. S. (Richard S.), Mohlke, K. L. (Karen L.), Saleheen, D. (Danish), Lee, J.-Y. (Jong-Young), Elliott, P. (Paul), Gierman, H. J. (Hinco J.), Willer, C. J. (Cristen J.), Franke, L. (Lude), Hovingh, G. K. (G. Kees), Taylor, K. D. (Kent D.), Dedoussis, G. (George), Sever, P. (Peter), Wong, A. (Andrew), Lind, L. (Lars), Assimes, T. L. (Themistocles L.), Njolstad, I. (Inger), Schwarz, P. E. (Peter E. H.), Langenberg, C. (Claudia), Snieder, H. (Harold), Caulfield, M. J. (Mark J.), Melander, E. (E.), Laakso, M. (Markku), Saltevo, J. (Juha), Rauramaa, R. (Rainer), Tuomilehto, J. (Jaakko), Ingelsson, E. (Erik), Lehtimaki, T. (Terho), Hveem, K. (Kristian), Palmas, W. (Walter), Marz, W. (Winfried), Kumar, M. (Meena), Salomaa, V. (Veikko), Chen, Y. I. (Yii-Der I.), Rotter, J. I. (Jerome I.), Froguel, P. (Philippe), Jarvelin, M.-R. (Marjo-Riitta), Lakatta, E. G. (Edward G.), Kuulasmaa, K. (Kari), Franks, P. W. (Paul W.), Hamsten, A. (Anders), Wichmann, H.-E. (H-Erich), Palmer, C. N. (Colin N. A.), Stefansson, K. (Kari), Ridker, P. M. (Paul M.), Loos, R. J. (Ruth J. F.), Chalcravarti, A. (Aravinda), Deloukas, P. (Panos), Morris, A. P. (Andrew P.), Newton-Cheh, C. (Christopher), and Munroe, P. B. (Patricia B.)
- Abstract
To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure–associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure–related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.
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- 2016
13. DNA methylation mediates the effect of maternal smoking during pregnancy on birthweight of the offspring
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Küpers, L.K. (Leanne), Xu, X. (Xiaojing), Jankipersadsing, S.A. (Soesma A.), Vaez, A. (Ahmad), La Bastide-van Gemert, S. (Sacha), Scholtens, S. (Salome), Nolte, I.M. (Ilja M.), Richmond, R.C. (Rebecca C.), Relton, C.L. (Caroline), Felix, J.F. (Janine), Duijts, L. (Liesbeth), Meurs, J.B.J. (Joyce) van, Tiemeier, H.W. (Henning), Jaddoe, V.W.V. (Vincent), Wang, X. (Xiaoling), Corpeleijn, W.E. (Willemijn), Snieder, H. (Harold), Küpers, L.K. (Leanne), Xu, X. (Xiaojing), Jankipersadsing, S.A. (Soesma A.), Vaez, A. (Ahmad), La Bastide-van Gemert, S. (Sacha), Scholtens, S. (Salome), Nolte, I.M. (Ilja M.), Richmond, R.C. (Rebecca C.), Relton, C.L. (Caroline), Felix, J.F. (Janine), Duijts, L. (Liesbeth), Meurs, J.B.J. (Joyce) van, Tiemeier, H.W. (Henning), Jaddoe, V.W.V. (Vincent), Wang, X. (Xiaoling), Corpeleijn, W.E. (Willemijn), and Snieder, H. (Harold)
- Abstract
Background: We examined whether the effect of maternal smoking during pregnancy on birthweight of the offspring was mediated by smoking-induced changes to DNA methylation in cord blood. Methods: First, we used cord blood of 129 Dutch children exposed to maternal smoking vs 126 unexposed to maternal and paternal smoking (53% male) participating in the GECKO Drenthe birth cohort. DNA methylation was measured using the Illumina HumanMethylation450 Beadchip. We performed an epigenome-wide association study for the association between maternal smoking and methylation followed by a mediation analysis of the top signals [false-discovery rate (FDR)<0.05]. We adjusted both analyses for maternal age, education, pre-pregnancy BMI, offspring's sex, gestational age and white blood cell composition. Secondly, in 175 exposed and 1248 unexposed newborns from two independent birth cohorts, we replicated and meta-analysed results of eight cytosine-phosphate-guanine (CpG) sites in the GFI1 gene, which showed the most robust mediation. Finally, we performed functional network and enrichment analysis. Results: We found 35 differentially methylated CpGs (FDR<0.05) in newborns exposed vs unexposed to smoking, of which 23 survived Bonferroni correction (P<1×10-7). These 23 CpGs mapped to eight genes: AHRR, GFI1, MYO1G, CYP1A1, NEUROG1, CNTNAP2, FRMD4A and LRP5. We observed partial confirmation as three of the eight CpGs in GFI1 replicated. These CpGs partly mediated the effect of maternal smoking on birthweight (Sobel P<0.05) in meta-analysis of GECKO and the two replication cohorts. Differential methylation of these three GFI1 CpGs explained 12-19% of the 202 g lower birthweight in smoking mothers. Functional enrichment analysis pointed towards activation of cell-mediated immunity. Conclusions: Maternal smoking during pregnancy was associated with cord blood methylation differences. We observed a potentially mediating role of methylation in the association between maternal smoking during
- Published
- 2015
- Full Text
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14. THE CARDIAC NICHE ROLE IN CARDIOMYOCYTE DIFFERENTIATION OF RAT BONE MARROW-DERIVED STROMAL CELLS: COMPARISON BETWEEN STATIC AND MICROFLUIDIC CELL CULTURE METHODS.
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Vaez, Seyed Ahmad, Ebrahimi-Barough, Somayeh, Soleimani, Masoud, Kolivand, Sedighe, Farzamfar, Saeed, Tafti, Seyed Hossein Ahmadi, Azami, Mahmoud, Noorbakhsh, Farshid, and Ai, Jafar
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HEART cells , *CELL differentiation , *LABORATORY rats , *STROMAL cells , *MICROFLUIDICS , *CELL culture - Abstract
Due to the restricted potential of the heart to regenerate its damaged region, stem cell therapy is a promising treatment modality for myocardial infarction. It has been shown that incubation of bone marrow-derived stromal cells (BMSCs) with initial steps of cardiac differentiation in vitro, can have a significant effect on their therapeutic potential to treat myocardial infarction. Based on these well-established principals we were encouraged to study the direct co-culture of rat BMSCs with neonatal mouse almost pure cardiomyocytes (APCs) and cardiac niche cells (CNCs) in static 2D and microfluidic cell culture systems. Our results showed that the difference regarding the beating rate in isolated APCs and CNCs in both 2D and the microfluidic system was not statistically significant for 30 days. No beat rate could be observed in induced BMSCs in all groups during experiment time. Except for BMSCs cultured alone in both experimental culture conditions, data obtained from Real-time PCR analysis showed that differentiated BMSCs in all co-cultured groups expressed GATA4, Nkx2.5, CX43, cTnI, cTnT, and ß-MHC during 4 weeks. BMSCs demonstrated a higher expression of these cardiac factors in microfluidic chips than those co-cultured in 24 well plates. Moreover, immunocytochemistry (ICC), also revealed the GATA4 expression in differentiated BMSCs in all co-cultured groups. It was found that, when combined with shear stress, co-culture with cardiomyocyte can differentiate BMSCs significantly toward cardiomyocyte rather than co-culture alone. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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15. Pleiotropic genes for metabolic syndrome and inflammation
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Kraja, A. (Aldi), Chasman, D.I. (Daniel), North, K.E. (Kari), Reiner, A. (Alexander), Yanek, L.R. (Lisa), Kilpeläinen, T.O. (Tuomas), Smith, J.A. (Jennifer), Dehghan, A. (Abbas), Dupuis, J. (Josée), Johnson, A.D. (Andrew), Feitosa, M.F. (Mary Furlan), Tekola-Ayele, F. (Fasil), Chu, A.Y. (Audrey), Nolte, I.M. (Ilja), Dastani, Z. (Zari), Morris, A.P. (Andrew), Pendergrass, S.A. (Sarah), Sun, Y.V. (Yan), Ritchie, M.D. (Marylyn), Vaez, A. (Ahmad), Lin, H. (Honghuang), Ligthart, S. (Symen), Marullo, L. (Letizia), Rohde, R. (Rebecca), Shao, Y. (Yaming), Ziegler, M.A. (Mark), Im, K.M. (Kate), Schnabel, R.B. (Renate), Jorgensen, T. (Torben), Jørgensen, M.E. (Marit), Hansen, T. (T.), Pedersen, O. (Oluf), Stolk, R.P. (Ronald), Snieder, H. (Harold), Hofman, A. (Albert), Uitterlinden, A.G. (André), Franco, O.H. (Oscar), Ikram, M.A. (Arfan), Richards, J.B. (Brent), Rotimi, C. (Charles), Wilson, J.G. (James), Lange, L.A. (Leslie), Ganesh, S.K. (Santhi), Nalls, M.A. (Michael), Rasmussen-Torvik, L.J. (Laura), Pankow, J.S. (James), Coresh, J. (Josef), Tang, W. (Weihong), Kao, W.-H.L. (Linda), Boerwinkle, E.A. (Eric), Morrison, A.C. (Alanna), Ridker, P.M. (Paul), Becker, D.M. (Diane), Rotter, J.I. (Jerome), Kardia, S.L.R. (Sharon), Loos, R.J.F. (Ruth), Larson, M.G. (Martin), Hsu, Y.-H. (Yi-Hsiang), Province, M.A. (Mike), Tracy, R.P. (Russell), Voight, B.F. (Benjamin), Vaidya, D. (Dhananjay), O'Donnell, C.J. (Christopher), Benjamin, E.J. (Emelia), Alizadeh, B.Z. (Behrooz), Prokopenko, I. (Inga), Meigs, J.B. (James), Borecki, I.B. (Ingrid), Kraja, A. (Aldi), Chasman, D.I. (Daniel), North, K.E. (Kari), Reiner, A. (Alexander), Yanek, L.R. (Lisa), Kilpeläinen, T.O. (Tuomas), Smith, J.A. (Jennifer), Dehghan, A. (Abbas), Dupuis, J. (Josée), Johnson, A.D. (Andrew), Feitosa, M.F. (Mary Furlan), Tekola-Ayele, F. (Fasil), Chu, A.Y. (Audrey), Nolte, I.M. (Ilja), Dastani, Z. (Zari), Morris, A.P. (Andrew), Pendergrass, S.A. (Sarah), Sun, Y.V. (Yan), Ritchie, M.D. (Marylyn), Vaez, A. (Ahmad), Lin, H. (Honghuang), Ligthart, S. (Symen), Marullo, L. (Letizia), Rohde, R. (Rebecca), Shao, Y. (Yaming), Ziegler, M.A. (Mark), Im, K.M. (Kate), Schnabel, R.B. (Renate), Jorgensen, T. (Torben), Jørgensen, M.E. (Marit), Hansen, T. (T.), Pedersen, O. (Oluf), Stolk, R.P. (Ronald), Snieder, H. (Harold), Hofman, A. (Albert), Uitterlinden, A.G. (André), Franco, O.H. (Oscar), Ikram, M.A. (Arfan), Richards, J.B. (Brent), Rotimi, C. (Charles), Wilson, J.G. (James), Lange, L.A. (Leslie), Ganesh, S.K. (Santhi), Nalls, M.A. (Michael), Rasmussen-Torvik, L.J. (Laura), Pankow, J.S. (James), Coresh, J. (Josef), Tang, W. (Weihong), Kao, W.-H.L. (Linda), Boerwinkle, E.A. (Eric), Morrison, A.C. (Alanna), Ridker, P.M. (Paul), Becker, D.M. (Diane), Rotter, J.I. (Jerome), Kardia, S.L.R. (Sharon), Loos, R.J.F. (Ruth), Larson, M.G. (Martin), Hsu, Y.-H. (Yi-Hsiang), Province, M.A. (Mike), Tracy, R.P. (Russell), Voight, B.F. (Benjamin), Vaidya, D. (Dhananjay), O'Donnell, C.J. (Christopher), Benjamin, E.J. (Emelia), Alizadeh, B.Z. (Behrooz), Prokopenko, I. (Inga), Meigs, J.B. (James), and Borecki, I.B. (Ingrid)
- Abstract
Metabolic syndrome (MetS) has become a health and financial burden worldwide. The MetS definition captures clustering of risk factors that predict higher risk for diabetes mellitus and cardiovascular disease. Our study hypothesis is that additional to genes influencing individual MetS risk factors, genetic variants exist that influence MetS and inflammatory markers forming a predisposing MetS genetic network. To test this hypothesis a staged approach was undertaken. (a) We analyzed 17 metabolic and inflammatory traits in more than 85,500 participants from 14 large epidemiological studies within the Cross Consortia Pleiotropy Group. Individuals classified with MetS (NCEP definition), versus those without, showed on average significantly different levels for most inflammatory markers studied. (b) Paired average correlations between 8 metabolic traits and 9 inflammatory markers from the same studies as above, estimated with two methods, and factor analyses on large simulated data, helped in identifying 8 combinations of traits for follow-up
- Published
- 2014
- Full Text
- View/download PDF
16. Discovery and fine mapping of serum protein loci through transethnic meta-analysis
- Author
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Franceschini, N. (Nora), Rooij, F.J.A. (Frank) van, Prins, B.P. (Bram), Feitosa, M.F. (Mary Furlan), Karakas, M. (Mahir), Eckfeldt, J.H. (John), Folsom, A.R. (Aaron), Kopp, J. (Jeffrey), Vaez, A. (Ahmad), Andrews, J.S. (Jeanette), Baumert, J. (Jens), Boraska, V. (Vesna), Broer, L. (Linda), Hayward, C. (Caroline), Ngwa, J.S., Okada, Y. (Yukinori), Polasek, O. (Ozren), Westra, H.J. (Harm-Jan), Wang, Y.A. (Ying), Del Greco, F. (Fabiola), Glazer, N.L. (Nicole), Kapur, K. (Karen), Kema, I.P. (Ido), Lopez, L.M. (Lorna), Schillert, A. (Arne), Smith, A.V. (Davey), Winkler, C.A. (Cheryl), Zgaga, L. (Lina), Bandinelli, S. (Stefania), Bergmann, S.M. (Sven), Boban, M. (Mladen), Bochud, M. (Murielle), Chen, Y.D. (Y.), Davies, G. (Gail), Dehghan, A. (Abbas), Ding, J. (Jingzhong), Doering, A. (Angela), Durda, J.P. (J. Peter), Ferrucci, L. (Luigi), Franco, O.H. (Oscar), Franke, L. (Lude), Gunjaca, G. (Grog), Hofman, A. (Albert), Hsu, F.-C. (Fang-Chi), Kolcic, I. (Ivana), Kraja, A. (Aldi), Kubo, M. (Michiaki), Lackner, K.J. (Karl), Launer, L.J. (Lenore), Loehr, L.R. (Laura), Li, G. (Guo), Meisinger, C. (Christa), Nakamura, Y. (Yusuke), Schwienbacher, C. (Christine), Starr, J.M. (John), Takahashi, A. (Atsushi), Torlak, V. (Vesela), Uitterlinden, A.G. (André), Vitart, V. (Veronique), Waldenberger, M. (Melanie), Wild, P.S. (Philipp), Kirin, M. (Mirna), Zeller, T. (Tanja), Zemunik, T. (Tatijana), Zhang, Q. (Qunyuan), Ziegler, A. (Andreas), Blankenberg, S. (Stefan), Boerwinkle, E.A. (Eric), Borecki, I.B. (Ingrid), Campbell, H. (Harry), Deary, I.J. (Ian), Frayling, T.M. (Timothy), Gieger, C. (Christian), Harris, T.B. (Tamara), Hicks, A.A. (Andrew), Koenig, W. (Wolfgang), O'Donnell, C.J. (Christopher), Fox, C. (Craig), Pramstaller, P.P. (Peter Paul), Psaty, B.M. (Bruce), Reiner, A. (Alexander), Rotter, J.I. (Jerome), Rudan, I. (Igor), Snieder, H. (Harold), Tanaka, T. (Toshiko), Duijn, C.M. (Cornelia) van, Vollenweider, P. (Peter), Waeber, G. (Gérard), Wilson, J.F. (James), Witteman, J.C.M. (Jacqueline), Wolffenbuttel, B.H.R. (Bruce), Wright, A.F. (Alan), Wu, Q. (Qingyu), Liu, Y. (YongMei), Jenny, N.S. (Nancy), North, K.E. (Kari), Felix, J.F. (Janine), Alizadeh, B.Z. (Behrooz), Cupples, L.A. (Adrienne), Perry, J.R.B. (John), Morris, A.P. (Andrew), Franceschini, N. (Nora), Rooij, F.J.A. (Frank) van, Prins, B.P. (Bram), Feitosa, M.F. (Mary Furlan), Karakas, M. (Mahir), Eckfeldt, J.H. (John), Folsom, A.R. (Aaron), Kopp, J. (Jeffrey), Vaez, A. (Ahmad), Andrews, J.S. (Jeanette), Baumert, J. (Jens), Boraska, V. (Vesna), Broer, L. (Linda), Hayward, C. (Caroline), Ngwa, J.S., Okada, Y. (Yukinori), Polasek, O. (Ozren), Westra, H.J. (Harm-Jan), Wang, Y.A. (Ying), Del Greco, F. (Fabiola), Glazer, N.L. (Nicole), Kapur, K. (Karen), Kema, I.P. (Ido), Lopez, L.M. (Lorna), Schillert, A. (Arne), Smith, A.V. (Davey), Winkler, C.A. (Cheryl), Zgaga, L. (Lina), Bandinelli, S. (Stefania), Bergmann, S.M. (Sven), Boban, M. (Mladen), Bochud, M. (Murielle), Chen, Y.D. (Y.), Davies, G. (Gail), Dehghan, A. (Abbas), Ding, J. (Jingzhong), Doering, A. (Angela), Durda, J.P. (J. Peter), Ferrucci, L. (Luigi), Franco, O.H. (Oscar), Franke, L. (Lude), Gunjaca, G. (Grog), Hofman, A. (Albert), Hsu, F.-C. (Fang-Chi), Kolcic, I. (Ivana), Kraja, A. (Aldi), Kubo, M. (Michiaki), Lackner, K.J. (Karl), Launer, L.J. (Lenore), Loehr, L.R. (Laura), Li, G. (Guo), Meisinger, C. (Christa), Nakamura, Y. (Yusuke), Schwienbacher, C. (Christine), Starr, J.M. (John), Takahashi, A. (Atsushi), Torlak, V. (Vesela), Uitterlinden, A.G. (André), Vitart, V. (Veronique), Waldenberger, M. (Melanie), Wild, P.S. (Philipp), Kirin, M. (Mirna), Zeller, T. (Tanja), Zemunik, T. (Tatijana), Zhang, Q. (Qunyuan), Ziegler, A. (Andreas), Blankenberg, S. (Stefan), Boerwinkle, E.A. (Eric), Borecki, I.B. (Ingrid), Campbell, H. (Harry), Deary, I.J. (Ian), Frayling, T.M. (Timothy), Gieger, C. (Christian), Harris, T.B. (Tamara), Hicks, A.A. (Andrew), Koenig, W. (Wolfgang), O'Donnell, C.J. (Christopher), Fox, C. (Craig), Pramstaller, P.P. (Peter Paul), Psaty, B.M. (Bruce), Reiner, A. (Alexander), Rotter, J.I. (Jerome), Rudan, I. (Igor), Snieder, H. (Harold), Tanaka, T. (Toshiko), Duijn, C.M. (Cornelia) van, Vollenweider, P. (Peter), Waeber, G. (Gérard), Wilson, J.F. (James), Witteman, J.C.M. (Jacqueline), Wolffenbuttel, B.H.R. (Bruce), Wright, A.F. (Alan), Wu, Q. (Qingyu), Liu, Y. (YongMei), Jenny, N.S. (Nancy), North, K.E. (Kari), Felix, J.F. (Janine), Alizadeh, B.Z. (Behrooz), Cupples, L.A. (Adrienne), Perry, J.R.B. (John), and Morris, A.P. (Andrew)
- Abstract
Many disorders are associated with altered serum protein concentrations, including malnutrition, cancer, and cardiovascular, kidney, and inflammatory diseases. Although these protein concentrations are highly heritable, relatively little is known about their underlying genetic determinants. Through transethnic meta-analysis of European-ancestry and Japanese genome-wide association studies, we identified six loci at genome-wide significance (p < 5 × 10-8) for serum albumin (HPN-SCN1B, GCKR-FNDC4, SERPINF2-WDR81, TNFRSF11A-ZCCHC2, FRMD5-WDR76, and RPS11-FCGRT, in up to 53,190 European-ancestry and 9,380 Japanese individuals) and three loci for total protein (TNFRS13B, 6q21.3, and ELL2, in up to 25,539 European-ancestry and 10,168 Japanese individuals). We observed little evidence of heterogeneity in allelic effects at these loci between groups of European and Japanese ancestry but obtained substantial improvements in the resolution of fine mapping of potential causal variants by leveraging transethnic differences in the distribution of linkage disequilibrium. We demonstrated a functional role for the most strongly associated serum albumin locus, HPN, for which Hpn knockout mice manifest low plasma albumin concentrations.
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- 2012
- Full Text
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17. Effect of Cholesterol, Iron and Vitamin E on Protamine Deficiency and DNA Fragmentation of Male Rabbit Sperm.
- Author
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Ghasemi, Nazem, Dashti, Gholam-Reza, Amoozgar, Fatimah, and Vaez, Seyed-Ahmad
- Abstract
Background: The role of vitamin E as an antioxidant and iron-containing compounds on DNA is not well defined. So, recent study was carried out to determine the role of vitamin E and iron, as both separate and combined effect on sperm protamine deficiency and DNA fragmentation in male rabbits. Methods: This study included 42 male rabbits which were randomly divided into seven groups each containing six rabbits.They were all treated under special diets for 6 weeks. After this period the animals were anesthetized and sacrificed .The epididymis duct and vas deferens were dissected and their sperms were extracted from it by Ham's f10 solution. Sperm DNA fragmentation and protamine deficiency were evaluated by the acridine orange and chromomycin A3 staining, respectively. Findings: The mean values of protamine deficiency and DNA fragmentation were significantly higher in group that concomitant use of cholesterol and iron. In addition, Vitamin E as an antioxidant agent has a significant effect in reducing these damages. Conclusion: Vitamin E as an antioxidant, decrease sperm DNA damage resulting from the consumption of foods high in cholesterol and iron. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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