204 results on '"Mononen, N"'
Search Results
2. Regulation of NC886 RNAs is associated with cardiometabolic risk factors, death and stroke
- Author
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Rajić, S., primary, Marttila, S., additional, Hutri-Kähönen, N., additional, Kähönen, M., additional, Lehtimäki, T., additional, Lyytikäinen, L.-P., additional, Mishra, P., additional, Mononen, N., additional, Raitakari, O., additional, Waldenberger, M., additional, Delerue, T., additional, März, W., additional, Kleber, M., additional, Harville, E., additional, Zhang, R., additional, and Raitoharju, E., additional
- Published
- 2023
- Full Text
- View/download PDF
3. Identification of blood modular genome-wide gene expression biomarkers of cardiovascular health and depression in the young finns study
- Author
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Mishra, B., primary, Raitoharju, E., additional, Mononen, N., additional, Viikari, J., additional, Juonala, M., additional, Hutri-Kähönen, N., additional, Kähönen, M., additional, Raitakari, O., additional, Lehtimäki, T., additional, and Mishra, P., additional
- Published
- 2023
- Full Text
- View/download PDF
4. Genetic insights into resting heart rate and its role in cardiovascular disease.
- Author
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Vegte, Y.J. van de, Eppinga, R.N., Ende, M.Y. van der, Hagemeijer, Y.P., Mahendran, Y., Salfati, E., Smith, A.V., Tan, V.Y., Arking, D.E., Ntalla, I., Appel, E.V., Schurmann, C., Brody, J.A., Rueedi, R., Polasek, O., Sveinbjornsson, G., Lecoeur, C., Ladenvall, C., Zhao, J.H., Isaacs, A., Wang, L., Luan, Jian'an, Hwang, S.J., Mononen, N., Auro, K., Jackson, A.U., Bielak, L.F., Zeng, L., Shah, N., Nethander, M., Campbell, A., Rankinen, T., Pechlivanis, S., Qi, L., Zhao, Wei, Rizzi, F., Tanaka, T., Robino, A., Cocca, M., Lange, L., Müller-Nurasyid, M., Roselli, C., Zhang, W, Kleber, M.E., Guo, X., Lin, H.J., Pavani, F., Galesloot, T.E., Noordam, R., Milaneschi, Y., Schraut, K.E., Hoed, M. den, Degenhardt, F., Trompet, S., Berg, M.E. van den, Pistis, G., Tham, Y.C., Weiss, S., Sim, X.S., Li, H.L., Most, P.J. van der, Nolte, I.M., Lyytikäinen, L.P., Said, M.A., Witte, D.R., Iribarren, C., Launer, L., Ring, S.M., Vries, P.S. de, Sever, P., Linneberg, A., Bottinger, E.P., Padmanabhan, S., Psaty, B.M., Sotoodehnia, N., Kolcic, I., Arnar, D.O., Gudbjartsson, D.F., Holm, H., Balkau, B., Silva, C.T., Newton-Cheh, C.H., Nikus, K., Salo, P., Mohlke, K.L., Peyser, P.A., Schunkert, H., Lorentzon, M., Lahti, J., Rao, D.C., Cornelis, M.C., Faul, J.D., Smith, J.A., Stolarz-Skrzypek, K., Bandinelli, S., Concas, M.P., Sinagra, G., Meitinger, T., Waldenberger, M., Sinner, M.F., Strauch, K., Delgado, G.E., Taylor, K.D., Yao, J., Foco, L., Melander, O., Graaf, J. de, Mutsert, R. de, Geus, E.J.C. de, Johansson, Å., Joshi, P.K., Lind, L., Franke, A., Macfarlane, P.W., Tarasov, K.V., Tan, N., Felix, S.B., Tai, E.S., Quek, D.Q., Snieder, H., Ormel, J., Ingelsson, M., Lindgren, C., Morris, A.P., Raitakari, O.T., Hansen, T., Assimes, T., Gudnason, V., Timpson, N.J., Morrison, A.C., Munroe, P.B., Strachan, D.P., Grarup, N., Loos, R.J.F., Heckbert, S.R., Vollenweider, P., Hayward, C., Stefansson, K., Froguel, P., Groop, L., Wareham, N.J., Duijn, C.M. van, Feitosa, M.F., O'Donnell, C.J., Kähönen, M., Perola, M., Boehnke, M., Kardia, S.L.R., Erdmann, J., Palmer, C.N.A., Ohlsson, C., Porteous, D.J., Eriksson, J.G., Bouchard, C., Moebus, S., Kraft, P., Weir, D.R., Cusi, D., Ferrucci, L., Ulivi, S., Girotto, G., Correa, A., Kääb, S., Peters, A., Chambers, J.C., Kooner, J.S., März, W., Rotter, J.I., Hicks, A.A., Smith, J.G., Kiemeney, L.A.L.M., Mook-Kanamori, D.O., Penninx, B.W.J.H., Gyllensten, U., Wilson, J.F., Burgess, S., Sundström, J., Lieb, W., Jukema, J.W., Eijgelsheim, M., Lakatta, E.L.M., Cheng, C.Y., Dörr, M., Wong, T.Y., Sabanayagam, C., Oldehinkel, A.J., Riese, H., Lehtimäki, T., Verweij, N., Harst, P. van der, Vegte, Y.J. van de, Eppinga, R.N., Ende, M.Y. van der, Hagemeijer, Y.P., Mahendran, Y., Salfati, E., Smith, A.V., Tan, V.Y., Arking, D.E., Ntalla, I., Appel, E.V., Schurmann, C., Brody, J.A., Rueedi, R., Polasek, O., Sveinbjornsson, G., Lecoeur, C., Ladenvall, C., Zhao, J.H., Isaacs, A., Wang, L., Luan, Jian'an, Hwang, S.J., Mononen, N., Auro, K., Jackson, A.U., Bielak, L.F., Zeng, L., Shah, N., Nethander, M., Campbell, A., Rankinen, T., Pechlivanis, S., Qi, L., Zhao, Wei, Rizzi, F., Tanaka, T., Robino, A., Cocca, M., Lange, L., Müller-Nurasyid, M., Roselli, C., Zhang, W, Kleber, M.E., Guo, X., Lin, H.J., Pavani, F., Galesloot, T.E., Noordam, R., Milaneschi, Y., Schraut, K.E., Hoed, M. den, Degenhardt, F., Trompet, S., Berg, M.E. van den, Pistis, G., Tham, Y.C., Weiss, S., Sim, X.S., Li, H.L., Most, P.J. van der, Nolte, I.M., Lyytikäinen, L.P., Said, M.A., Witte, D.R., Iribarren, C., Launer, L., Ring, S.M., Vries, P.S. de, Sever, P., Linneberg, A., Bottinger, E.P., Padmanabhan, S., Psaty, B.M., Sotoodehnia, N., Kolcic, I., Arnar, D.O., Gudbjartsson, D.F., Holm, H., Balkau, B., Silva, C.T., Newton-Cheh, C.H., Nikus, K., Salo, P., Mohlke, K.L., Peyser, P.A., Schunkert, H., Lorentzon, M., Lahti, J., Rao, D.C., Cornelis, M.C., Faul, J.D., Smith, J.A., Stolarz-Skrzypek, K., Bandinelli, S., Concas, M.P., Sinagra, G., Meitinger, T., Waldenberger, M., Sinner, M.F., Strauch, K., Delgado, G.E., Taylor, K.D., Yao, J., Foco, L., Melander, O., Graaf, J. de, Mutsert, R. de, Geus, E.J.C. de, Johansson, Å., Joshi, P.K., Lind, L., Franke, A., Macfarlane, P.W., Tarasov, K.V., Tan, N., Felix, S.B., Tai, E.S., Quek, D.Q., Snieder, H., Ormel, J., Ingelsson, M., Lindgren, C., Morris, A.P., Raitakari, O.T., Hansen, T., Assimes, T., Gudnason, V., Timpson, N.J., Morrison, A.C., Munroe, P.B., Strachan, D.P., Grarup, N., Loos, R.J.F., Heckbert, S.R., Vollenweider, P., Hayward, C., Stefansson, K., Froguel, P., Groop, L., Wareham, N.J., Duijn, C.M. van, Feitosa, M.F., O'Donnell, C.J., Kähönen, M., Perola, M., Boehnke, M., Kardia, S.L.R., Erdmann, J., Palmer, C.N.A., Ohlsson, C., Porteous, D.J., Eriksson, J.G., Bouchard, C., Moebus, S., Kraft, P., Weir, D.R., Cusi, D., Ferrucci, L., Ulivi, S., Girotto, G., Correa, A., Kääb, S., Peters, A., Chambers, J.C., Kooner, J.S., März, W., Rotter, J.I., Hicks, A.A., Smith, J.G., Kiemeney, L.A.L.M., Mook-Kanamori, D.O., Penninx, B.W.J.H., Gyllensten, U., Wilson, J.F., Burgess, S., Sundström, J., Lieb, W., Jukema, J.W., Eijgelsheim, M., Lakatta, E.L.M., Cheng, C.Y., Dörr, M., Wong, T.Y., Sabanayagam, C., Oldehinkel, A.J., Riese, H., Lehtimäki, T., Verweij, N., and Harst, P. van der
- Abstract
Contains fulltext : 296013.pdf (Publisher’s version ) (Open Access), Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.
- Published
- 2023
5. Association study of the HTR2C, leptin and adiponectin genes and serum marker analyses in clozapine treated long-term patients with schizophrenia
- Author
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Klemettilä, J.-P., Kampman, O., Seppälä, N., Viikki, M., Hämäläinen, M., Moilanen, E., Mononen, N., Lehtimäki, T., and Leinonen, E.
- Published
- 2015
- Full Text
- View/download PDF
6. The effect of nuclear factor 1B polymorphisms and valproate use on clozapine metabolism
- Author
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Rask, S.M., primary, Solismaa, A., additional, Ahola-Olli, A., additional, Lyytikäinen, L.P., additional, Mononen, N., additional, Lehtimäki, T., additional, and Kampman, O., additional
- Published
- 2023
- Full Text
- View/download PDF
7. Genetic and epigenetic regulation of nc886 RNA levels and their association to cardiometabolic phenotypes
- Author
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Rajic, S., Marttila, S., Mishra, P., Mononen, N., Raitakari, O., Lyytikäinen, L.-P., Kähönen, M., Hutri-Kähönen, N., Waldenberger, M., Lehtimäki, T., and Raitoharju, E.
- Published
- 2022
- Full Text
- View/download PDF
8. Neuropeptide Y polymorphism increases the risk for asthma in overweight subjects; protection from atherosclerosis in asthmatic subjects – The cardiovascular risk in young Finns study
- Author
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Jaakkola, U., Kakko, T., Juonala, M., Lehtimäki, T., Viikari, J., Jääskeläinen, A.E., Mononen, N., Kähönen, M., Koskinen, T., Keltikangas-Järvinen, L., Raitakari, O., and Kallio, J.
- Published
- 2012
- Full Text
- View/download PDF
9. The trajectory of the blood DNA methylome ageing rate is largely set before adulthood: evidence from two longitudinal studies
- Author
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Kananen, L., Marttila, S., Nevalainen, T., Kummola, L., Junttila, I., Mononen, N., Kähönen, M., Raitakari, O. T., Hervonen, A., Jylhä, M., Lehtimäki, T., Hurme, M., and Jylhävä, J.
- Published
- 2016
- Full Text
- View/download PDF
10. Association of C-reactive protein (CRP) gene allelic variants with serum CRP levels and hypertension in Turkish adults
- Author
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Komurcu-Bayrak, E., Erginel-Unaltuna, N., Onat, A., Ozsait, B., Eklund, C., Hurme, M., Mononen, N., Laaksonen, R., Hergenc, G., and Lehtimäki, T.
- Published
- 2009
- Full Text
- View/download PDF
11. Medicines Information Research in Finland in 2000-2013: A Systematic Review
- Author
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Mononen, N. M., Järvinen, R., Enlund, H., Airaksinen, M. S., Kleme, J., and Hämeen-Anttila, K.
- Published
- 2014
- Full Text
- View/download PDF
12. Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline
- Author
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Gorski, M. (Mathias), Jung, B. (Bettina), Li, Y. (Yong), Matias-Garcia, P.R. (Pamela R.), Wuttke, M. (Matthias), Coassin, S. (Stefan), Thio, C.H.L. (Chris H.L.), Kleber, M.E. (Marcus E.), Winkler, T.W. (Thomas W.), Wanner, V. (Veronika), Chai, J.-F. (Jin-Fang), Chu, A.Y. (Audrey Y), Cocca, M. (Massimiliano), Feitosa, M.F. (Mary Furlan), Ghasemi, S. (Sahar), Hoppmann, A. (Anselm), Horn, K. (Katrin), Li, M. (Man), Nutile, T. (Teresa), Scholz, M. (Markus), Sieber, K.B. (Karsten B.), Teumer, A. (Alexander), Tin, A. (Adrienne), Wang, J. (Judy), Tayo, B. (Bamidele), Ahluwalia, T.S. (Tarunveer Singh), Almgren, P. (Peter), Bakker, S.J.L. (Stephan), Banas, B. (Bernhard), Bansal, N. (Nisha), Biggs, M.L. (M.), Boerwinkle, E.A. (Eric), Bottinger, E.P. (Erwin), Brenner, H. (Hermann), Carroll, R.J. (Robert J.), Chalmers, J. (John), Chee, M.-L. (Miao-Li), Chee, M.-L. (Miao-Ling), Cheng, C.-Y. (Ching-Yu), Coresh, J. (Josef), de Borst, M.H. (Martin H.), Degenhardt, F. (Frauke), Eckardt, K.-U. (Kai-Uwe), Endlich, K. (Karlhans), Franke, A. (Andre), Freitag-Wolf, S. (Sandra), Gampawar, P. (Piyush), Gansevoort, R.T. (Ron), Ghanbari, M. (Mohsen), Gieger, C. (Christian), Hamet, P. (Pavel), Ho, K. (Kevin), Hofer, E. (Edith), Holleczek, B. (B.), Xian Foo, V.H. (Valencia Hui), Hutri-Kähönen, N. (Nina), Hwang, S.-J. (Shih-Jen), Ikram, M.A. (Arfan), Josyula, N.S. (Navya Shilpa), Kähönen, M. (Mika), Khor, C.C., Koenig, W. (Wolfgang), Kramer, H. (Holly), Krämer, B.K. (Bernhard), Kuhnel, B. (Brigitte), Lange, L.A. (Leslie A.), Lehtimäki, T. (Terho), Lieb, W. (Wolfgang), Alizadeh, B.Z. (Behrooz), Boezen, H.M. (H. Marike), Franke, L. (Lude), van der Harst, P. (Pim), Matullo, G., Rots, M.G. (M.), Snieder, H. (Harold), Swertz, M. (Morris), Wolffenbuttel, B.H.R. (Bruce), Wijmenga, C. (Cisca), Abecasis, G.R. (Gonçalo), Baras, A. (Aris), Cantor, M. (Michael), Coppola, G. (Giovanni), Economides, A. (Aris), Lotta, L.A. (Luca A.), Overton, J.D. (John D.), Reid, J.G. (Jeffrey G.), Shuldiner, A. (Alan), Beechert, C. (Christina), Forsythe, C. (Caitlin), Fuller, E.D. (Erin D.), Gu, Z. (Zhenhua), Lattari, M. (Michael), Lopez, A. (Alexander), Schleicher, T.D. (Thomas D.), Padilla, M.S. (Maria Sotiropoulos), Toledo, K. (Karina), Widom, L. (Louis), Wolf, S.E. (Sarah E.), Pradhan, M. (Manasi), Manoochehri, K. (Kia), Ulloa, R.H. (Ricardo H.), Bai, X. (Xiaodong), Balasubramanian, S. (Suganthi), Barnard, L. (Leland), Blumenfeld, A. (Andrew), Eom, G. (Gisu), Habegger, L. (Lukas), Hawes, A. (Alicia), Khalid, S. (Shareef), Maxwell, E.K. (Evan K.), Salerno, W. (William), Staples, J.C. (Jeffrey C.), Jones, M.B. (Marcus B.), Mitnaul, L.J. (Lyndon), Loos, R.J.F. (Ruth J.F.), Lukas, M.A. (Mary Ann), Lyytikäinen, L.-P. (Leo-Pekka), Meisinger, C. (Christa), Meitinger, T. (Thomas), Melander, O. (Olle), Milaneschi, Y. (Yuri), Mishra, P.P. (Pashupati P.), Mononen, N. (Nina), Mychaleckyj, J.C. (Josyf), Nadkarni, G. (Girish), Nauck, M. (Matthias), Nikus, K. (Kjell), Ning, B. (Boting), Nolte, I.M. (Ilja), O'Donoghue, M.L. (Michelle L.), Orho-Melander, M. (Marju), Pendergrass, S.A. (Sarah), Penninx, B.W.J.H. (Brenda), Preuss, M. (Michael), Psaty, B.M. (Bruce M.), Raffield, L.M. (Laura M.), Raitakari, O. (Olli), Rettig, R. (Rainer), Rheinberger, M. (Myriam), Rice, K.M. (Kenneth M.), Rosenkranz, A.R. (Alexander R.), Rossing, K., Rotter, J.I. (Jerome I.), Sabanayagam, C. (Charumathi), Schmidt, H. (Helena), Schmidt, R. (Reinhold), Schöttker, B. (Ben), Schulz, C.A. (Christina Alexandra), Sedaghat, S. (Sanaz), Shaffer, C.M. (Christian M.), Strauch, K. (Konstantin), Szymczak, S. (Silke), Taylor, K.D. (Kent D.), Tremblay, J. (Johanne), Chaker, L. (Layal), Most, P.J. (Peter) van der, Verweij, N. (Niek), Völker, U. (Uwe), Waldenberger, M. (Melanie), Wallentin, L.C. (Lars), Waterworth, D.M. (Dawn M.), White, H.D. (Harvey), Wilson, J.G. (James G.), Wong, T.-Y. (Tien-Yin), Woodward, M. (Mark), Yang, Q. (Qiong), Yasuda, M. (Masayuki), Yerges-Armstrong, L.M. (Laura), Zhang, Y. (Yan), Wanner, C. (Christoph), Böger, C.A. (Carsten), Köttgen, A. (Anna), Kronenberg, F. (Florian), Penninx, B.W.J.H., Heid, I.M. (Iris), Gorski, M. (Mathias), Jung, B. (Bettina), Li, Y. (Yong), Matias-Garcia, P.R. (Pamela R.), Wuttke, M. (Matthias), Coassin, S. (Stefan), Thio, C.H.L. (Chris H.L.), Kleber, M.E. (Marcus E.), Winkler, T.W. (Thomas W.), Wanner, V. (Veronika), Chai, J.-F. (Jin-Fang), Chu, A.Y. (Audrey Y), Cocca, M. (Massimiliano), Feitosa, M.F. (Mary Furlan), Ghasemi, S. (Sahar), Hoppmann, A. (Anselm), Horn, K. (Katrin), Li, M. (Man), Nutile, T. (Teresa), Scholz, M. (Markus), Sieber, K.B. (Karsten B.), Teumer, A. (Alexander), Tin, A. (Adrienne), Wang, J. (Judy), Tayo, B. (Bamidele), Ahluwalia, T.S. (Tarunveer Singh), Almgren, P. (Peter), Bakker, S.J.L. (Stephan), Banas, B. (Bernhard), Bansal, N. (Nisha), Biggs, M.L. (M.), Boerwinkle, E.A. (Eric), Bottinger, E.P. (Erwin), Brenner, H. (Hermann), Carroll, R.J. (Robert J.), Chalmers, J. (John), Chee, M.-L. (Miao-Li), Chee, M.-L. (Miao-Ling), Cheng, C.-Y. (Ching-Yu), Coresh, J. (Josef), de Borst, M.H. (Martin H.), Degenhardt, F. (Frauke), Eckardt, K.-U. (Kai-Uwe), Endlich, K. (Karlhans), Franke, A. (Andre), Freitag-Wolf, S. (Sandra), Gampawar, P. (Piyush), Gansevoort, R.T. (Ron), Ghanbari, M. (Mohsen), Gieger, C. (Christian), Hamet, P. (Pavel), Ho, K. (Kevin), Hofer, E. (Edith), Holleczek, B. (B.), Xian Foo, V.H. (Valencia Hui), Hutri-Kähönen, N. (Nina), Hwang, S.-J. (Shih-Jen), Ikram, M.A. (Arfan), Josyula, N.S. (Navya Shilpa), Kähönen, M. (Mika), Khor, C.C., Koenig, W. (Wolfgang), Kramer, H. (Holly), Krämer, B.K. (Bernhard), Kuhnel, B. (Brigitte), Lange, L.A. (Leslie A.), Lehtimäki, T. (Terho), Lieb, W. (Wolfgang), Alizadeh, B.Z. (Behrooz), Boezen, H.M. (H. Marike), Franke, L. (Lude), van der Harst, P. (Pim), Matullo, G., Rots, M.G. (M.), Snieder, H. (Harold), Swertz, M. (Morris), Wolffenbuttel, B.H.R. (Bruce), Wijmenga, C. (Cisca), Abecasis, G.R. (Gonçalo), Baras, A. (Aris), Cantor, M. (Michael), Coppola, G. (Giovanni), Economides, A. (Aris), Lotta, L.A. (Luca A.), Overton, J.D. (John D.), Reid, J.G. (Jeffrey G.), Shuldiner, A. (Alan), Beechert, C. (Christina), Forsythe, C. (Caitlin), Fuller, E.D. (Erin D.), Gu, Z. (Zhenhua), Lattari, M. (Michael), Lopez, A. (Alexander), Schleicher, T.D. (Thomas D.), Padilla, M.S. (Maria Sotiropoulos), Toledo, K. (Karina), Widom, L. (Louis), Wolf, S.E. (Sarah E.), Pradhan, M. (Manasi), Manoochehri, K. (Kia), Ulloa, R.H. (Ricardo H.), Bai, X. (Xiaodong), Balasubramanian, S. (Suganthi), Barnard, L. (Leland), Blumenfeld, A. (Andrew), Eom, G. (Gisu), Habegger, L. (Lukas), Hawes, A. (Alicia), Khalid, S. (Shareef), Maxwell, E.K. (Evan K.), Salerno, W. (William), Staples, J.C. (Jeffrey C.), Jones, M.B. (Marcus B.), Mitnaul, L.J. (Lyndon), Loos, R.J.F. (Ruth J.F.), Lukas, M.A. (Mary Ann), Lyytikäinen, L.-P. (Leo-Pekka), Meisinger, C. (Christa), Meitinger, T. (Thomas), Melander, O. (Olle), Milaneschi, Y. (Yuri), Mishra, P.P. (Pashupati P.), Mononen, N. (Nina), Mychaleckyj, J.C. (Josyf), Nadkarni, G. (Girish), Nauck, M. (Matthias), Nikus, K. (Kjell), Ning, B. (Boting), Nolte, I.M. (Ilja), O'Donoghue, M.L. (Michelle L.), Orho-Melander, M. (Marju), Pendergrass, S.A. (Sarah), Penninx, B.W.J.H. (Brenda), Preuss, M. (Michael), Psaty, B.M. (Bruce M.), Raffield, L.M. (Laura M.), Raitakari, O. (Olli), Rettig, R. (Rainer), Rheinberger, M. (Myriam), Rice, K.M. (Kenneth M.), Rosenkranz, A.R. (Alexander R.), Rossing, K., Rotter, J.I. (Jerome I.), Sabanayagam, C. (Charumathi), Schmidt, H. (Helena), Schmidt, R. (Reinhold), Schöttker, B. (Ben), Schulz, C.A. (Christina Alexandra), Sedaghat, S. (Sanaz), Shaffer, C.M. (Christian M.), Strauch, K. (Konstantin), Szymczak, S. (Silke), Taylor, K.D. (Kent D.), Tremblay, J. (Johanne), Chaker, L. (Layal), Most, P.J. (Peter) van der, Verweij, N. (Niek), Völker, U. (Uwe), Waldenberger, M. (Melanie), Wallentin, L.C. (Lars), Waterworth, D.M. (Dawn M.), White, H.D. (Harvey), Wilson, J.G. (James G.), Wong, T.-Y. (Tien-Yin), Woodward, M. (Mark), Yang, Q. (Qiong), Yasuda, M. (Masayuki), Yerges-Armstrong, L.M. (Laura), Zhang, Y. (Yan), Wanner, C. (Christoph), Böger, C.A. (Carsten), Köttgen, A. (Anna), Kronenberg, F. (Florian), Penninx, B.W.J.H., and Heid, I.M. (Iris)
- Abstract
Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m2/year or more (“Rapid3”; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m2 at follow-up among those with eGFRcrea 60 mL/min/1.73m2 or more at baseline (“CKDi25”; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized varia
- Published
- 2021
- Full Text
- View/download PDF
13. Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline
- Author
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Gorski, M, Jung, B, Li, Y, Matias-Garcia, PR, Wuttke, M, Coassin, S, Thio, CHL, Kleber, ME, Winkler, TW, Wanner, V, Chai, JF, Chu, AY, Cocca, M, Feitosa, MF, Ghasemi, S, Hoppmann, A, van der Horn, K, Li, M, Nutile, T, Scholz, M (Markus), Sieber, KB, Teumer, A, Tin, A, Wang, J, Tayo, BO, Ahluwalia, TS, Almgren, P, Bakker, SJL, Banas, B, Bansal, N, Biggs, ML, Boerwinkle, E, Bottinger, EP, Brenner, H, Carroll, R J, Chalmers, J, Chee, ML, Chee, MLA, Cheng, CY (Ching-Yu), Coresh, J, de Borst, MH, Degenhardt, F, Eckardt, KU, Endlich, K, Franke, A, Freitag-Wolf, S, Gampawar, P, Gansevoort, RT, Ghanbari, Mohsen, Gieger, C, Hamet, P, Ho, K, Hofer, E, Holleczek, B, Foo, VHX, Hutri-Kahonen, N, Hwang, SJ, Ikram, Arfan, Josyula, NS, Kahonen, M, Khor, CC, Koenig, W, Kramer, H, Kramer, BK, Kuhnel, B, Lange, LA, Lehtimaki, T, Lieb, W, Loos, RJF, Lukas, MA, Lyytikainen, LP, Meisinger, C, Meitinger, T, Melander, O, Milaneschi, Y, Mishra, PP, Mononen, N, Mychaleckyj, JC, Nadkarni, GN, Nauck, M, Nikus, K, Ning, B, Nolte, IM, O'Donoghue, ML, Orho-Melander, M, Pendergrass, SA, Penninx, B, Preuss, MH, Psaty, BM, Raffield, L M, Raitakari, OT, Rettig, R, Rheinberger, M, Rice, KM, Rosenkranz, AR, Rossing, P, Rotter, JI, Sabanayagam, C, Schmidt, H, Schmidt, R, Schottker, B, Schulz, C A, Sedaghat, Sanaz, Shaffer, CM, Strauch, K, Szymczak, S, Taylor, KD, Tremblay, J, Chaker, Layal, van der Harst, P, van der Most, PJ, Verweij, N, Volker, U, Waldenberger, M, Wallentin, L, Waterworth, DM, White, HD, Wilson, JG, Wong, TY, Woodward, M, Yang, Q, Yasuda, M, Yerges-Armstrong, LM, Zhang, Y, Snieder, H, Wanner, C, Boger, CA, Kottgen, A, Kronenberg, F, Pattaro, C, Heid, IM, Gorski, M, Jung, B, Li, Y, Matias-Garcia, PR, Wuttke, M, Coassin, S, Thio, CHL, Kleber, ME, Winkler, TW, Wanner, V, Chai, JF, Chu, AY, Cocca, M, Feitosa, MF, Ghasemi, S, Hoppmann, A, van der Horn, K, Li, M, Nutile, T, Scholz, M (Markus), Sieber, KB, Teumer, A, Tin, A, Wang, J, Tayo, BO, Ahluwalia, TS, Almgren, P, Bakker, SJL, Banas, B, Bansal, N, Biggs, ML, Boerwinkle, E, Bottinger, EP, Brenner, H, Carroll, R J, Chalmers, J, Chee, ML, Chee, MLA, Cheng, CY (Ching-Yu), Coresh, J, de Borst, MH, Degenhardt, F, Eckardt, KU, Endlich, K, Franke, A, Freitag-Wolf, S, Gampawar, P, Gansevoort, RT, Ghanbari, Mohsen, Gieger, C, Hamet, P, Ho, K, Hofer, E, Holleczek, B, Foo, VHX, Hutri-Kahonen, N, Hwang, SJ, Ikram, Arfan, Josyula, NS, Kahonen, M, Khor, CC, Koenig, W, Kramer, H, Kramer, BK, Kuhnel, B, Lange, LA, Lehtimaki, T, Lieb, W, Loos, RJF, Lukas, MA, Lyytikainen, LP, Meisinger, C, Meitinger, T, Melander, O, Milaneschi, Y, Mishra, PP, Mononen, N, Mychaleckyj, JC, Nadkarni, GN, Nauck, M, Nikus, K, Ning, B, Nolte, IM, O'Donoghue, ML, Orho-Melander, M, Pendergrass, SA, Penninx, B, Preuss, MH, Psaty, BM, Raffield, L M, Raitakari, OT, Rettig, R, Rheinberger, M, Rice, KM, Rosenkranz, AR, Rossing, P, Rotter, JI, Sabanayagam, C, Schmidt, H, Schmidt, R, Schottker, B, Schulz, C A, Sedaghat, Sanaz, Shaffer, CM, Strauch, K, Szymczak, S, Taylor, KD, Tremblay, J, Chaker, Layal, van der Harst, P, van der Most, PJ, Verweij, N, Volker, U, Waldenberger, M, Wallentin, L, Waterworth, DM, White, HD, Wilson, JG, Wong, TY, Woodward, M, Yang, Q, Yasuda, M, Yerges-Armstrong, LM, Zhang, Y, Snieder, H, Wanner, C, Boger, CA, Kottgen, A, Kronenberg, F, Pattaro, C, and Heid, IM
- Abstract
Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m2/year or more (“Rapid3”; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m2 at follow-up among those with eGFRcrea 60 mL/min/1.73m2 or more at baseline (“CKDi25”; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or LARP4B. Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
- Published
- 2021
14. Effect of Genetic Polymorphisms in CA6 Gene on the Expression and Catalytic Activity of Human Salivary Carbonic Anhydrase VI
- Author
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Aidar, M., Marques, Rocha M.R., Valjakka, J., Mononen, N., Lehtimäki, T., Parkkila, S., de Souza, A. P., and Line, Peres S.R.P.
- Published
- 2013
- Full Text
- View/download PDF
15. EFFECTS OF FTO (FAT MASS AND OBESITY ASSOCIATED) GENE POLYMORPHISMS ON TURKISH ADULT RISK FACTOR (TARF) STUDY POPULATION: H03
- Author
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Yüzbasiogullari, A B, Komurcu-Bayrak, E, Onat, A, Hergenc, G, Mononen, N, Laaksonen, R, Kähönen, M, Lehtimäki, T, and Erginel-Unaltuna, N
- Published
- 2010
16. The Polygenic and Monogenic Basis of Blood Traits and Diseases
- Author
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Vuckovic, D. (Dragana), Bao, E.L. (Erik L.), Akbari, P. (Parsa), Lareau, C.A. (Caleb A.), Mousas, A. (Abdou), Jiang, T. (Tao), Chen, M.-H. (Ming-Huei), Raffield, L.M. (Laura M.), Tardaguila, M. (Manuel), Huffman, J.E. (Jennifer E.), Ritchie, S.C. (Scott C.), Megy, K. (Karyn), Ponstingl, H. (Hannes), Penkett, C.J. (Christopher J.), Albers, P.K. (Patrick K.), Wigdor, E.M. (Emilie M.), Sakaue, S. (Saori), Moscati, A. (Arden), Manansala, R. (Regina), Lo, K.S., Qian, H. (Huijun), Akiyama, M. (Masato), Bartz, T.M. (Traci M.), Ben-Shlomo, Y. (Yoav), Beswick, A. (Andrew), Bork-Jensen, J. (Jette), Bottinger, E.P. (Erwin), Brody, J.A. (Jennifer A.), Rooij, F.J.A. (Frank) van, Chitrala, K.N. (Kumaraswamy N.), Wilson, P.W.F. (Peter W.F.), Choquet, H. (Hélène), Danesh, J. (John), Angelantonio, E. (Emanuele) di, Dimou, N. (Niki), Ding, J. (Jingzhong), Elliott, P. (Paul), Esko, T. (Tõnu), Evans, M.K. (Michele), Felix, S.B. (Stephan Burkhard), Floyd, J.S. (James S.), Broer, L. (Linda), Grarup, N. (Niels), Guo, M.H. (Michael H.), Guo, Q. (Qi), Greinacher, A. (Andreas), Haessler, J. (Jeff), Hansen, T. (Torben), Howson, J.M.M. (Joanna M.M.), Huang, W. (Wei), Jorgenson, E. (Eric), Kacprowski, T. (Tim), Kähönen, M. (Mika), Kamatani, Y. (Yoichiro), Kanai, M. (Masahiro), Karthikeyan, S. (Savita), Koskeridis, F. (Fotios), Lange, L.A. (Leslie A.), Lehtimäki, T. (Terho), Linneberg, A. (Allan), Liu, Y. (YongMei), Lyytikäinen, L.-P. (Leo-Pekka), Manichaikul, A. (Ani), Matsuda, K. (Koichi), Mohlke, K.L. (Karen L.), Mononen, N. (Nina), Murakami, Y. (Yoshinori), Nadkarni, G. (Girish), Nikus, K. (Kjell), Pankratz, V.S. (Shane), Pedersen, O. (Oluf), Preuss, M. (Michael), Psaty, B.M. (Bruce), Raitakari, O. (Olli), Rich, S.S. (Stephen), Rodriguez, B.A.T. (Benjamin A.T.), Rosen, J.D. (Jonathan D.), Rotter, J.I. (Jerome I.), Schubert, P. (Petra), Spracklen, C.N. (Cassandra N.), Surendran, P. (Praveen), Tang, H. (Hua), Tardif, J.-C. (Jean-Claude), Ghanbari, M. (Mohsen), Völker, U. (Uwe), Völzke, H. (Henry), Watkins, N.A. (Nicholas A.), Weiss, S. (Stefan), Cai, N. (Na), Kundu, K. (Kousik), Watt, S.B. (Stephen B.), Walter, K. (Klaudia), Zonderman, A.B. (Alan B.), Cho, K. (Kelly), Li, Y. (Yun), Loos, R.J.F. (Ruth), Knight, J.C. (Julian), Georges, M. (Michel), Stegle, O. (Oliver), Evangelou, E. (Evangelos), Okada, Y. (Yukinori), Roberts, D.J. (David J.), Inouye, M. (Michael), Johnson, A.D. (Andrew), Auer, P.L. (Paul L.), Astle, W.J. (William J.), Reiner, A.P. (Alexander P.), Butterworth, A.S. (Adam S.), Ouwehand, W.H. (Willem), Lettre, G. (Guillaume), Sankaran, V.G. (Vijay G.), Soranzo, N. (Nicole), Vuckovic, D. (Dragana), Bao, E.L. (Erik L.), Akbari, P. (Parsa), Lareau, C.A. (Caleb A.), Mousas, A. (Abdou), Jiang, T. (Tao), Chen, M.-H. (Ming-Huei), Raffield, L.M. (Laura M.), Tardaguila, M. (Manuel), Huffman, J.E. (Jennifer E.), Ritchie, S.C. (Scott C.), Megy, K. (Karyn), Ponstingl, H. (Hannes), Penkett, C.J. (Christopher J.), Albers, P.K. (Patrick K.), Wigdor, E.M. (Emilie M.), Sakaue, S. (Saori), Moscati, A. (Arden), Manansala, R. (Regina), Lo, K.S., Qian, H. (Huijun), Akiyama, M. (Masato), Bartz, T.M. (Traci M.), Ben-Shlomo, Y. (Yoav), Beswick, A. (Andrew), Bork-Jensen, J. (Jette), Bottinger, E.P. (Erwin), Brody, J.A. (Jennifer A.), Rooij, F.J.A. (Frank) van, Chitrala, K.N. (Kumaraswamy N.), Wilson, P.W.F. (Peter W.F.), Choquet, H. (Hélène), Danesh, J. (John), Angelantonio, E. (Emanuele) di, Dimou, N. (Niki), Ding, J. (Jingzhong), Elliott, P. (Paul), Esko, T. (Tõnu), Evans, M.K. (Michele), Felix, S.B. (Stephan Burkhard), Floyd, J.S. (James S.), Broer, L. (Linda), Grarup, N. (Niels), Guo, M.H. (Michael H.), Guo, Q. (Qi), Greinacher, A. (Andreas), Haessler, J. (Jeff), Hansen, T. (Torben), Howson, J.M.M. (Joanna M.M.), Huang, W. (Wei), Jorgenson, E. (Eric), Kacprowski, T. (Tim), Kähönen, M. (Mika), Kamatani, Y. (Yoichiro), Kanai, M. (Masahiro), Karthikeyan, S. (Savita), Koskeridis, F. (Fotios), Lange, L.A. (Leslie A.), Lehtimäki, T. (Terho), Linneberg, A. (Allan), Liu, Y. (YongMei), Lyytikäinen, L.-P. (Leo-Pekka), Manichaikul, A. (Ani), Matsuda, K. (Koichi), Mohlke, K.L. (Karen L.), Mononen, N. (Nina), Murakami, Y. (Yoshinori), Nadkarni, G. (Girish), Nikus, K. (Kjell), Pankratz, V.S. (Shane), Pedersen, O. (Oluf), Preuss, M. (Michael), Psaty, B.M. (Bruce), Raitakari, O. (Olli), Rich, S.S. (Stephen), Rodriguez, B.A.T. (Benjamin A.T.), Rosen, J.D. (Jonathan D.), Rotter, J.I. (Jerome I.), Schubert, P. (Petra), Spracklen, C.N. (Cassandra N.), Surendran, P. (Praveen), Tang, H. (Hua), Tardif, J.-C. (Jean-Claude), Ghanbari, M. (Mohsen), Völker, U. (Uwe), Völzke, H. (Henry), Watkins, N.A. (Nicholas A.), Weiss, S. (Stefan), Cai, N. (Na), Kundu, K. (Kousik), Watt, S.B. (Stephen B.), Walter, K. (Klaudia), Zonderman, A.B. (Alan B.), Cho, K. (Kelly), Li, Y. (Yun), Loos, R.J.F. (Ruth), Knight, J.C. (Julian), Georges, M. (Michel), Stegle, O. (Oliver), Evangelou, E. (Evangelos), Okada, Y. (Yukinori), Roberts, D.J. (David J.), Inouye, M. (Michael), Johnson, A.D. (Andrew), Auer, P.L. (Paul L.), Astle, W.J. (William J.), Reiner, A.P. (Alexander P.), Butterworth, A.S. (Adam S.), Ouwehand, W.H. (Willem), Lettre, G. (Guillaume), Sankaran, V.G. (Vijay G.), and Soranzo, N. (Nicole)
- Abstract
Blood cells play essential roles in human health, underpinning physiological processes such as immunity, oxygen transport, and clotting, which when perturbed cause a significant global health burden. Here we integrate data from UK Biobank and a large-scale international collaborative effort, including data for 563,085 European ancestry participants, and discover 5,106 new genetic variants independently associated with 29 blood cell phenotypes covering a range of variation impacting hematopoiesis. We holistically characterize the genetic architecture of hematopoiesis, assess the relevance of the omnigenic model to blood cell phenotypes, delineate relevant hematopoietic cell states influenced by regulatory genetic variants and gene networks, identify novel splice-altering variants mediating the associations, and assess the polygenic prediction potential for blood traits and clinical disorders at the interface of complex and Mendelian genetics. These results show the power of large-scale blood cell trait GWAS to interrogate clinically meaningful variants across a wide allelic spectrum of human variation. Analysis of blood cell traits in the UK Biobank and other cohorts illuminates the full genetic architecture of hematopoietic phenotypes, with evidence supporting the omnigenic model for complex traits and linking polygenic burden with monogenic blood diseases.
- Published
- 2020
- Full Text
- View/download PDF
17. Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction
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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
- Full Text
- View/download PDF
18. The Polygenic and Monogenic Basis of Blood Traits and Diseases
- Author
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Vuckovic, D, Bao, EL, Akbari, P, Lareau, CA, Mousas, A, Jiang, T, Chen, M-H, Raffield, LM, Tardaguila, M, Huffman, JE, Ritchie, SC, Megy, K, Ponstingl, H, Penkett, CJ, Albers, PK, Wigdor, EM, Sakaue, S, Moscati, A, Manansala, R, Lo, KS, Qian, H, Akiyama, M, Bartz, TM, Ben-Shlomo, Y, Beswick, A, Bork-Jensen, J, Bottinger, EP, Brody, JA, van Rooij, FJA, Chitrala, KN, Wilson, PWF, Choquet, H, Danesh, J, Di Angelantonio, E, Dimou, N, Ding, J, Elliott, P, Esko, T, Evans, MK, Felix, SB, Floyd, JS, Broer, L, Grarup, N, Guo, MH, Guo, Q, Greinacher, A, Haessler, J, Hansen, T, Howson, JMM, Huang, W, Jorgenson, E, Kacprowski, T, Kahonen, M, Kamatani, Y, Kanai, M, Karthikeyan, S, Koskeridis, F, Lange, LA, Lehtimaki, T, Linneberg, A, Liu, Y, Lyytikainen, L-P, Manichaikul, A, Matsuda, K, Mohlke, KL, Mononen, N, Murakami, Y, Nadkarni, GN, Nikus, K, Pankratz, N, Pedersen, O, Preuss, M, Psaty, BM, Raitakari, OT, Rich, SS, Rodriguez, BAT, Rosen, JD, Rotter, JI, Schubert, P, Spracklen, CN, Surendran, P, Tang, H, Tardif, J-C, Ghanbari, M, Volker, U, Volzke, H, Watkins, NA, Weiss, S, Cai, N, Kundu, K, Watt, SB, Walter, K, Zonderman, AB, Cho, K, Li, Y, Loos, RJF, Knight, JC, Georges, M, Stegle, O, Evangelou, E, Okada, Y, Roberts, DJ, Inouye, M, Johnson, AD, Auer, PL, Astle, WJ, Reiner, AP, Butterworth, AS, Ouwehand, WH, Lettre, G, Sankaran, VG, Soranzo, N, Vuckovic, D, Bao, EL, Akbari, P, Lareau, CA, Mousas, A, Jiang, T, Chen, M-H, Raffield, LM, Tardaguila, M, Huffman, JE, Ritchie, SC, Megy, K, Ponstingl, H, Penkett, CJ, Albers, PK, Wigdor, EM, Sakaue, S, Moscati, A, Manansala, R, Lo, KS, Qian, H, Akiyama, M, Bartz, TM, Ben-Shlomo, Y, Beswick, A, Bork-Jensen, J, Bottinger, EP, Brody, JA, van Rooij, FJA, Chitrala, KN, Wilson, PWF, Choquet, H, Danesh, J, Di Angelantonio, E, Dimou, N, Ding, J, Elliott, P, Esko, T, Evans, MK, Felix, SB, Floyd, JS, Broer, L, Grarup, N, Guo, MH, Guo, Q, Greinacher, A, Haessler, J, Hansen, T, Howson, JMM, Huang, W, Jorgenson, E, Kacprowski, T, Kahonen, M, Kamatani, Y, Kanai, M, Karthikeyan, S, Koskeridis, F, Lange, LA, Lehtimaki, T, Linneberg, A, Liu, Y, Lyytikainen, L-P, Manichaikul, A, Matsuda, K, Mohlke, KL, Mononen, N, Murakami, Y, Nadkarni, GN, Nikus, K, Pankratz, N, Pedersen, O, Preuss, M, Psaty, BM, Raitakari, OT, Rich, SS, Rodriguez, BAT, Rosen, JD, Rotter, JI, Schubert, P, Spracklen, CN, Surendran, P, Tang, H, Tardif, J-C, Ghanbari, M, Volker, U, Volzke, H, Watkins, NA, Weiss, S, Cai, N, Kundu, K, Watt, SB, Walter, K, Zonderman, AB, Cho, K, Li, Y, Loos, RJF, Knight, JC, Georges, M, Stegle, O, Evangelou, E, Okada, Y, Roberts, DJ, Inouye, M, Johnson, AD, Auer, PL, Astle, WJ, Reiner, AP, Butterworth, AS, Ouwehand, WH, Lettre, G, Sankaran, VG, and Soranzo, N
- Abstract
Blood cells play essential roles in human health, underpinning physiological processes such as immunity, oxygen transport, and clotting, which when perturbed cause a significant global health burden. Here we integrate data from UK Biobank and a large-scale international collaborative effort, including data for 563,085 European ancestry participants, and discover 5,106 new genetic variants independently associated with 29 blood cell phenotypes covering a range of variation impacting hematopoiesis. We holistically characterize the genetic architecture of hematopoiesis, assess the relevance of the omnigenic model to blood cell phenotypes, delineate relevant hematopoietic cell states influenced by regulatory genetic variants and gene networks, identify novel splice-altering variants mediating the associations, and assess the polygenic prediction potential for blood traits and clinical disorders at the interface of complex and Mendelian genetics. These results show the power of large-scale blood cell trait GWAS to interrogate clinically meaningful variants across a wide allelic spectrum of human variation.
- Published
- 2020
19. BRCA1 and BRCA2 mutations have no major role in predisposition to prostate cancer in Finland
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Ikonen, T, Matikainen, M P, Syrjäkoski, K, Mononen, N, Koivisto, P A, Rökman, A, Seppälä, E H, Kallioniemi, O-P, Tammela, T L J, and Schleutker, J
- Published
- 2003
20. The effect of apolipoprotein E polymorphism on serum metabolome:a population-based 10-year follow-up study
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Karjalainen, J.-P. (Juho-Pekka), Mononen, N. (Nina), Hutri-Kähönen, N. (Nina), Lehtimäki, M. (Miikael), Juonala, M. (Markus), Ala-Korpela, M. (Mika), Kähönen, M. (Mika), Raitakari, O. (Olli), Lehtimäki, T. (Terho), Karjalainen, J.-P. (Juho-Pekka), Mononen, N. (Nina), Hutri-Kähönen, N. (Nina), Lehtimäki, M. (Miikael), Juonala, M. (Markus), Ala-Korpela, M. (Mika), Kähönen, M. (Mika), Raitakari, O. (Olli), and Lehtimäki, T. (Terho)
- Abstract
Apolipoprotein E (apoE) is the key regulator of plasma lipids, mediating altered functionalities in lipoprotein metabolism – affecting the risk of coronary artery (CAD) and Alzheimer’s diseases, as well as longevity. Searching pathways influenced by apoE prior to adverse manifestations, we utilized a metabolome dataset of 228 nuclear-magnetic-resonance-measured serum parameters with a 10-year follow-up from the population-based Young Finns Study cohort of 2,234 apoE-genotyped (rs7412, rs429358) adults, aged 24–39 at baseline. At the end of our follow-up, by limiting FDR-corrected p < 0.05, regression analyses revealed 180/228 apoE-polymorphism-related associations with the studied metabolites, in all subjects – without indications of apoE x sex interactions. Across all measured apoE- and apoB-containing lipoproteins, ε4 allele had consistently atherogenic and ε2 protective effect on particle concentrations of free/esterified cholesterol, triglycerides, phospholipids and total lipids. As novel findings, ε4 associated with glycoprotein acetyls, LDL-diameter and isoleucine – all reported biomarkers of CAD-risk, inflammation, diabetes and total mortality. ApoE-subgroup differences persisted through our 10-year follow-up, although some variation of individual metabolite levels was noticed. In conclusion, apoE polymorphism associate with a complex metabolic change, including aberrations in multiple novel biomarkers related to elevated cardiometabolic and all-cause mortality risk, extending our understanding about the role of apoE in health and disease.
- Published
- 2019
21. Genetic and environmental perturbations lead to regulatory decoherence
- Author
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Lea, A. (Amanda), Subramaniam, M. (Meena), Ko, A. (Arthur), Lehtimäki, T. (Terho), Raitoharju, E. (Emma), Kähönen, M. (Mika), Seppälä, I. (Ilkka), Mononen, N. (Nina), Raitakari, O. T. (Olli T.), Ala-Korpela, M. (Mika), Pajukanta, P. (Päivi), Zaitlen, N. (Noah), Ayroles, J. F. (Julien F.), Lea, A. (Amanda), Subramaniam, M. (Meena), Ko, A. (Arthur), Lehtimäki, T. (Terho), Raitoharju, E. (Emma), Kähönen, M. (Mika), Seppälä, I. (Ilkka), Mononen, N. (Nina), Raitakari, O. T. (Olli T.), Ala-Korpela, M. (Mika), Pajukanta, P. (Päivi), Zaitlen, N. (Noah), and Ayroles, J. F. (Julien F.)
- Abstract
Correlation among traits is a fundamental feature of biological systems that remains difficult to study. To address this problem, we developed a flexible approach that allows us to identify factors associated with inter-individual variation in correlation. We use data from three human cohorts to study the effects of genetic and environmental variation on correlations among mRNA transcripts and among NMR metabolites. We first show that environmental exposures (infection and disease) lead to a systematic loss of correlation, which we define as ‘decoherence’. Using longitudinal data, we show that decoherent metabolites are better predictors of whether someone will develop metabolic syndrome than metabolites commonly used as biomarkers of this disease. Finally, we demonstrate that correlation itself is under genetic control by mapping hundreds of ‘correlation quantitative trait loci (QTLs)’. Together, this work furthers our understanding of how and why coordinated biological processes break down, and points to a potential role for decoherence in disease.
- Published
- 2019
22. Interethnic analyses of blood pressure loci in populations of East Asian and European descent
- Author
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Takeuchi, F, Akiyama, M, Matoba, N, Lyytikäinen, L-P, Lehtimäki, T, Kähönen, M, Mononen, N, Kjell, N, Lääketieteen ja biotieteiden tiedekunta - Faculty of Medicine and Life Sciences, and Tampere University
- Subjects
Sisätaudit - Internal medicine ,Biokemia, solu- ja molekyylibiologia - Biochemistry, cell and molecular biology - Published
- 2018
23. The rs2516839 variation of USF1 gene is associated with 4‐year mortality of nonagenarian women: The Vitality 90+ study
- Author
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Ozsait‐Selcuk, B., primary, Komurcu‐Bayrak, E., additional, Jylhä, M., additional, Luukkaala, T., additional, Perola, M., additional, Kristiansson, K., additional, Mononen, N., additional, Hurme, M., additional, Kähönen, M., additional, Goebeler, S., additional, Laaksonen, R., additional, Hervonen, A., additional, Erginel‐Unaltuna, N., additional, Karhunen, P.J., additional, and Lehtimäki, T., additional
- Published
- 2018
- Full Text
- View/download PDF
24. ExomeChip-Wide Analysis of 95 626 Individuals Identifies 10 Novel Loci Associated With QT and JT Intervals
- Author
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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
- Full Text
- View/download PDF
25. ExomeChip-Wide Analysis of 95 626 Individuals Identifies 10 Novel Loci Associated With QT and JT Intervals
- Author
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Bihlmeyer, NA, Brody, JA, Smith, AV, Warren, HR, Lin, HH, Isaacs, Aaron, Liu, CT, Marten, J, Radmanesh, F, Hall, LM, Grarup, N, Mei, H, Muller-Nurasyid, M, Huffman, JE, Verweij, N, Guo, XQ, Yao, J, Li-Gao, RF, van den Berg, Marten, Weiss, S, Prins, BP, van Setten, J, Haessler, J, Lyytikainen, LP, Li, M, Alonso, A, Soliman, EZ, Bis, JC, Austin, T, Chen, YDI, Psaty, BM, Harrris, TB, Launer, LJ, Padmanabhan, S, Dominiczak, A, Huang, PL, Xie, ZJ, Ellinor, PT, Kors, Jan, Campbell, A (Archie), Murray, AD, Nelson, CP, Tobin, MD, Bork-Jensen, J, Hansen, T, Pedersen, O, Linneberg, A, Sinner, MF, Peters, A, Waldenberger, M, Meitinger, T, Perz, S, Kolcic, I, Rudan, I, de Boer, RA, Meer, P, Lin, H J, Taylor, KD, de Mutsert, R, Trompet, S, Jukema, JW, Maan, AC, Stricker, Bruno, Rivadeneira, Fernando, Uitterlinden, André, Volker, U, Homuth, G, Volzke, H, Felix, SB, Mangino, M, Spector, TD, Bots, ML, Perez, M, Raitakari, OT, Kahonen, M, Mononen, N, Gudnason, V, Munroe, PB, Lubitz, SA, Duijn, Cornelia, Newton-Cheh, CH, Hayward, C, Rosand, J, Samani, NJ, Kanters, JK, Wilson, JG, Kaab, S, Polasek, O, van der Harst, P, Heckbert, SR, Rotter, JI, Mook, Dennis, Eij-Gelsheim, M, Dorr, M, Jamshidi, Y, Asselbergs, FW, Kooperberg, C, Lehtimaki, T, Arking, DE, Sotoodehnia, N, Bihlmeyer, NA, Brody, JA, Smith, AV, Warren, HR, Lin, HH, Isaacs, Aaron, Liu, CT, Marten, J, Radmanesh, F, Hall, LM, Grarup, N, Mei, H, Muller-Nurasyid, M, Huffman, JE, Verweij, N, Guo, XQ, Yao, J, Li-Gao, RF, van den Berg, Marten, Weiss, S, Prins, BP, van Setten, J, Haessler, J, Lyytikainen, LP, Li, M, Alonso, A, Soliman, EZ, Bis, JC, Austin, T, Chen, YDI, Psaty, BM, Harrris, TB, Launer, LJ, Padmanabhan, S, Dominiczak, A, Huang, PL, Xie, ZJ, Ellinor, PT, Kors, Jan, Campbell, A (Archie), Murray, AD, Nelson, CP, Tobin, MD, Bork-Jensen, J, Hansen, T, Pedersen, O, Linneberg, A, Sinner, MF, Peters, A, Waldenberger, M, Meitinger, T, Perz, S, Kolcic, I, Rudan, I, de Boer, RA, Meer, P, Lin, H J, Taylor, KD, de Mutsert, R, Trompet, S, Jukema, JW, Maan, AC, Stricker, Bruno, Rivadeneira, Fernando, Uitterlinden, André, Volker, U, Homuth, G, Volzke, H, Felix, SB, Mangino, M, Spector, TD, Bots, ML, Perez, M, Raitakari, OT, Kahonen, M, Mononen, N, Gudnason, V, Munroe, PB, Lubitz, SA, Duijn, Cornelia, Newton-Cheh, CH, Hayward, C, Rosand, J, Samani, NJ, Kanters, JK, Wilson, JG, Kaab, S, Polasek, O, van der Harst, P, Heckbert, SR, Rotter, JI, Mook, Dennis, Eij-Gelsheim, M, Dorr, M, Jamshidi, Y, Asselbergs, FW, Kooperberg, C, Lehtimaki, T, Arking, DE, and Sotoodehnia, N
- Published
- 2018
26. Genetic loci associated with heart rate variability and their effects on cardiac disease risk
- Author
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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
27. Genetic loci associated with heart rate variability and their effects on cardiac disease risk
- Author
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Nolte, IM, Munoz, ML, Tragante, V, Amare, AT, Jansen, R, Vaez, A, Heyde, B, Avery, CL, Bis, JC, Dierckx, Bram, Dongen, J, Gogarten, SM, Goyette, P, Hernesniemi, J, Huikari, V, Hwang, SJ, Jaju, D, Kerr, KF, Kluttig, A, Krijthe, Bouwe, Kumar, J, van der Laan, SW, Lyytikainen, LP, Maihofer, AX, Minassian, A, van der Most, PJ, Muller-Nurasyid, M, Nivard, M, Salvi, E, Stewart, JD, Thayer, JF, Verweij, N, Wong, A, Zabaneh, D, Zafarmand, MH, Abdellaoui, A, Albarwani, S, Albert, C, Alonso, A, Ashar, F, Auvinen, J, Axelsson, T, Baker, DG, de Bakker, PIW, Barcella, M, Bayoumi, R, Bieringa, RJ, Boomsma, D, Boucher, G, Britton, AR, Christophersen, IE, Dietrich, A, Ehret, GB, Ellinor, PT, Eskola, M, Felix, Janine, Floras, JS, Franco Duran, OH, Friberg, P, Gademan, MGJ, Geyer, MA, Giedraitis, V, Hartman, CA, Hemerich, D, Hofman, Bert, Hottenga, JJ, Huikuri, H, Hutri-Kahonen, N, Juonala, M, Kiviniemi, AM, Kors, Jan, Kumari, M, Kuznetsova, T, Laurie, CC, Lefrandt, JD, Li, Y, Li, YY, Liao, DP, Limacher, MC, Lin, H J, Lindgren, CM, Lubitz, SA, Mahajan, A, McKnight, B, zu Schwabedissen, HM, Milaneschi, Y, Mononen, N, Morris, AP, Nalls, MA, Navis, G, Neijts, M, Nikus, K, North, KE, O'Connor, DT, Ormel, J, Perz, S, Peters, A, Psaty, BM, Raitakari, OT, Risbrough, VB, Sinner, MF, Siscovick, D, Smit, JH, Smith, NL, Soliman, EZ, Sotoodehnia, N, Staessen, JA, Stein, PK, Stilp, AM, Stolarz-Skrzypek, K, Strauch, K, Sundstrom, J, Swenne, CA, Syvanen, AC, Tardif, JC, Taylor, KD, Teumer, A, Thornton, TA, Tinker, LE, Uitterlinden, André, van Setten, J, Voss, A, Waldenberger, M, Wilhelmsen, KC, Willemsen, G, Wong, QN, Zhang, ZM, Zonderman, AB, Cusi, D, Evans, MK, Greiser, HK, van der Harst, P, Hassan, M, Ingelsson, E, Jarvelin, MR, Kaab, S, Kahonen, M, Kivimaki, M, Kooperberg, C, Kuh, D, Lehtimaki, T, Lind, L, Nievergelt, CM, O'Donnell, CJ, Oldehinkel, AJ, Penninx, B, Reiner, AP, Riese, H, van Roon, AM, Rioux, JD, Rotter, JI, Sofer, T, Stricker, Bruno, Tiemeier, Henning, Vrijkotte, TGM, Asselbergs, FW, Brundel, B, Heckbert, SR, Whitsel, EA, den Hoed, M, Snieder, H, de Geus, EJC, Nolte, IM, Munoz, ML, Tragante, V, Amare, AT, Jansen, R, Vaez, A, Heyde, B, Avery, CL, Bis, JC, Dierckx, Bram, Dongen, J, Gogarten, SM, Goyette, P, Hernesniemi, J, Huikari, V, Hwang, SJ, Jaju, D, Kerr, KF, Kluttig, A, Krijthe, Bouwe, Kumar, J, van der Laan, SW, Lyytikainen, LP, Maihofer, AX, Minassian, A, van der Most, PJ, Muller-Nurasyid, M, Nivard, M, Salvi, E, Stewart, JD, Thayer, JF, Verweij, N, Wong, A, Zabaneh, D, Zafarmand, MH, Abdellaoui, A, Albarwani, S, Albert, C, Alonso, A, Ashar, F, Auvinen, J, Axelsson, T, Baker, DG, de Bakker, PIW, Barcella, M, Bayoumi, R, Bieringa, RJ, Boomsma, D, Boucher, G, Britton, AR, Christophersen, IE, Dietrich, A, Ehret, GB, Ellinor, PT, Eskola, M, Felix, Janine, Floras, JS, Franco Duran, OH, Friberg, P, Gademan, MGJ, Geyer, MA, Giedraitis, V, Hartman, CA, Hemerich, D, Hofman, Bert, Hottenga, JJ, Huikuri, H, Hutri-Kahonen, N, Juonala, M, Kiviniemi, AM, Kors, Jan, Kumari, M, Kuznetsova, T, Laurie, CC, Lefrandt, JD, Li, Y, Li, YY, Liao, DP, Limacher, MC, Lin, H J, Lindgren, CM, Lubitz, SA, Mahajan, A, McKnight, B, zu Schwabedissen, HM, Milaneschi, Y, Mononen, N, Morris, AP, Nalls, MA, Navis, G, Neijts, M, Nikus, K, North, KE, O'Connor, DT, Ormel, J, Perz, S, Peters, A, Psaty, BM, Raitakari, OT, Risbrough, VB, Sinner, MF, Siscovick, D, Smit, JH, Smith, NL, Soliman, EZ, Sotoodehnia, N, Staessen, JA, Stein, PK, Stilp, AM, Stolarz-Skrzypek, K, Strauch, K, Sundstrom, J, Swenne, CA, Syvanen, AC, Tardif, JC, Taylor, KD, Teumer, A, Thornton, TA, Tinker, LE, Uitterlinden, André, van Setten, J, Voss, A, Waldenberger, M, Wilhelmsen, KC, Willemsen, G, Wong, QN, Zhang, ZM, Zonderman, AB, Cusi, D, Evans, MK, Greiser, HK, van der Harst, P, Hassan, M, Ingelsson, E, Jarvelin, MR, Kaab, S, Kahonen, M, Kivimaki, M, Kooperberg, C, Kuh, D, Lehtimaki, T, Lind, L, Nievergelt, CM, O'Donnell, CJ, Oldehinkel, AJ, Penninx, B, Reiner, AP, Riese, H, van Roon, AM, Rioux, JD, Rotter, JI, Sofer, T, Stricker, Bruno, Tiemeier, Henning, Vrijkotte, TGM, Asselbergs, FW, Brundel, B, Heckbert, SR, Whitsel, EA, den Hoed, M, Snieder, H, and de Geus, EJC
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- 2017
28. Association of 5-alpha-reductase gene (SRD5A2) with prostate cancer
- Author
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Mononen, N., Koivisto, P.A., Ikonen, T., Syrjakoski, K., Schleutker, J., Hyytinen, E., Tammela, T.L.J., and Kallioniemi, O.-P.
- Subjects
Genetic research -- Analysis ,Human genetics -- Research ,Prostate cancer -- Genetic aspects ,Biological sciences - Published
- 2000
29. Association of a novel E-Cadherin gene coding region SNP with prostate cancer in a large population-based study
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Koivisto, P.A., Ikonen, T., Matikainen, M., Mononen, N., Helin, H.J., Tommola, S., Tammela, T., Schleutker, J., and Kallioniemi, O-P.
- Subjects
Genetic research -- Analysis ,Stomach cancer -- Analysis ,Prostate cancer -- Analysis ,Biological sciences - Published
- 2000
30. Association Study of Arcuate Nucleus Neuropeptide Y Neuron Receptor Gene Variation And Serum Npy Levels in Clozapine Treated Patients With Schizophrenia
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Klemettilä, J.-P., primary, Kampman, O., additional, Solismaa, A., additional, Lyytikäinen, L.-P., additional, Seppälä, N., additional, Viikki, M., additional, Hämäläinen, M., additional, Moilanen, E., additional, Mononen, N., additional, Lehtimäki, T., additional, and Leinonen, E., additional
- Published
- 2016
- Full Text
- View/download PDF
31. The rs2516839 variation of USF1 gene is associated with 4‐year mortality of nonagenarian women: The Vitality 90+ study.
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Ozsait‐Selcuk, B., Komurcu‐Bayrak, E., Jylhä, M., Luukkaala, T., Perola, M., Kristiansson, K., Mononen, N., Hurme, M., Kähönen, M., Goebeler, S., Laaksonen, R., Hervonen, A., Erginel‐Unaltuna, N., Karhunen, P.J., and Lehtimäki, T.
- Subjects
TRANSCRIPTION factors ,IMMUNE response ,GENOTYPES ,NUCLEASES ,HAPLOTYPES - Abstract
Upstream transcription factor 1 (USF1) regulates the transcription of many genes related to cell and organism survival processes such as stress and immune response, regulation of cellular senesce, and carcinogenesis. In this study, our aim was to investigate the effect of USF1 single nucleotide variations (SNVs) on longevity in the Vitality 90+ study, a population‐based study of nonagenarians (90 ±1 years of age) living in the area of Tampere municipality, Finland. Altogether 509 voluntary nonagenarians (115 males, 394 females) were genotyped using the 5′‐nuclease assay for rs2774279G > A, rs2516839T > C, and rs2073658C > T SNVs. During the 4 years of follow‐up, the total mortality rate was 64.2%. In the study, we found that the frequency of C‐allele of rs2516839 among nonsurviving nonagenarians (52.5%) was higher than those who survived (41.2%; P = 0.0006, odds ratio = 1.575, 95% confidence interval [CI]: 1.215–2.041). Furthermore, carriage of this variation and its haplotypes had a significant gender by genotype interaction (P < 0.05) on mortality. Kaplan‐Meier log‐rank test during 4‐years of follow‐up showed significantly higher mortality rate in the case of CC genotype carriage than other genotype carriages in nonagenarian women (P < 0.0001). In addition, after adjusting for age in Cox regression analysis, cardiovascular disease, diabetes, infectious disease, dementia, and living place (nursing home or home), CC genotype of rs2516839T > C was found to be associated with shorter life expectancy in nonagenarian women (hazard ratio = 2.27; 95% CI, 1.34–3.85 P = 0.002). In conclusion, rs2516839 variation and related haplotypes of the USF1 gene are strongly related to all‐cause mortality in Finnish nonagenarians, especially among women. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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32. Genetic profiling using genome-wide significant coronary artery disease risk variants does not improve the prediction of subclinical atherosclerosis : The Cardiovascular Risk in Young Finns Study, the Bogalusa Heart Study and the Health 2000 Survey a meta-analysis of three independent studies
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Jussi Aleksi Hernesniemi, Seppälä, I., Lp, Lyytikäinen, Mononen, N., Niku Oksala, Hutri-Kähönen, N., Mika Kähönen, Terho Lehtimäki, Taittonen, L., Biolääketieteellisen teknologian yksikkö - Institute of Biomedical Technology, Lääketieteen yksikkö - School of Medicine, and University of Tampere
- Subjects
Biolääketieteet - Biomedicine ,cardiovascular diseases - Abstract
Background Genome-wide association studies (GWASs) have identified a large number of variants (SNPs) associating with an increased risk of coronary artery disease (CAD). Recently, the CARDIoGRAM consortium published a GWAS based on the largest study population so far. They successfully replicated twelve already known associations and discovered thirteen new SNPs associating with CAD. We examined whether the genetic profiling of these variants improves prediction of subclinical atherosclerosis – i.e., carotid intima-media thickness (CIMT) and carotid artery elasticity (CAE) – beyond classical risk factors. Subjects and Methods We genotyped 24 variants found in a population of European ancestry and measured CIMT and CAE in 2001 and 2007 from 2,081, and 2,015 subjects (aged 30–45 years in 2007) respectively, participating in the Cardiovascular Risk in Young Finns Study (YFS). The Bogalusa Heart Study (BHS; n = 1179) was used as a replication cohort (mean age of 37.5). For additional replication, a sub-sample of 5 SNPs was genotyped for 1,291 individuals aged 46–76 years participating in the Health 2000 population survey. We tested the impact of genetic risk score (GRS24SNP/CAD) calculated as a weighted (by allelic odds ratios for CAD) sum of CAD risk alleles from the studied 24 variants on CIMT, CAE, the incidence of carotid atherosclerosis and the progression of CIMT and CAE during a 6-year follow-up. Results CIMT or CAE did not significantly associate with GRS24SNP/CAD before or after adjusting for classical CAD risk factors (p>0.05 for all) in YFS or in the BHS. CIMT and CAE associated with only one SNP each in the YFS. The findings were not replicated in the replication cohorts. In the meta-analysis CIMT or CAE did not associate with any of the SNPs. Conclusion Genetic profiling, by using known CAD risk variants, should not improve risk stratification for subclinical atherosclerosis beyond conventional risk factors among healthy young adults. Public Library of Science open access
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- 2012
33. Aging-associated DNA methylation changes in middle-aged individuals: the Young Finns study
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Kananen, L., primary, Marttila, S., additional, Nevalainen, T., additional, Jylhävä, J., additional, Mononen, N., additional, Kähönen, M., additional, Raitakari, O. T., additional, Lehtimäki, T., additional, and Hurme, M., additional
- Published
- 2016
- Full Text
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34. Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization
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Arking, D, Pulit, S, Crotti, L, van der Harst, P, Munroe, P, Koopmann, T, Sotoodehnia, N, Rossin, E, Morley, M, Wang, X, Johnson, A, Lundby, A, Gudbjartsson, D, Noseworthy, P, Eijgelsheim, M, Bradford, Y, Tarasov, K, Dörr, M, Müller-Nurasyid, M, Lahtinen, A, Nolte, I, Smith, A, Bis, J, Isaacs, A, Newhouse, S, Evans, D, Post, W, Waggott, D, Lyytikäinen, L, Hicks, A, Eisele, L, Ellinghaus, D, Hayward, C, Navarro, P, Ulivi, S, Tanaka, T, Tester, D, Chatel, S, Gustafsson, S, Kumari, M, Morris, R, Naluai, A, Padmanabhan, S, Kluttig, A, Strohmer, B, Panayiotou, A, Torres, M, Knoflach, M, Hubacek, J, Slowikowski, K, Raychaudhuri, S, Kumar, R, Harris, T, Launer, L, Shuldiner, A, Alonso, A, Bader, J, Ehret, G, Huang, H, Kao, W, Strait, J, Macfarlane, P, Brown, M, Caulfield, M, Samani, N, Kronenberg, F, Willeit, J, Smith, J, Greiser, K, Meyer Zu Schwabedissen, H, Werdan, K, Carella, M, Zelante, L, Heckbert, S, Psaty, B, Rotter, J, Kolcic, I, Polašek, O, Wright, A, Griffin, M, Daly, M, Arnar, D, Hólm, H, Thorsteinsdottir, U, Denny, J, Roden, D, Zuvich, R, Emilsson, V, Plump, A, Larson, M, O'Donnell, C, Yin, X, Bobbo, M, D'Adamo, A, Iorio, A, Sinagra, G, Carracedo, A, Cummings, S, Nalls, M, Jula, A, Kontula, K, Marjamaa, A, Oikarinen, L, Perola, M, Porthan, K, Erbel, R, Hoffmann, P, Jöckel, K, Kälsch, H, Nöthen, M, den Hoed, M, Loos, R, Thelle, D, Gieger, C, Meitinger, T, Perz, S, Peters, A, Prucha, H, Sinner, M, Waldenberger, M, de Boer, R, Franke, L, van der Vleuten, P, Beckmann, B, Martens, E, Bardai, A, Hofman, N, Wilde, A, Behr, E, Dalageorgou, C, Giudicessi, J, Medeiros-Domingo, A, Kyndt, F, Probst, V, Ghidoni, A, Insolia, R, Hamilton, R, Scherer, S, Brandimarto, J, Margulies, K, Moravec, C, Greco, M, Fuchsberger, C, O'Connell, J, Lee, W, Watt, G, Campbell, H, Wild, S, El Mokhtari, N, Frey, N, Asselbergs, F, Mateo Leach, I, Navis, G, van den Berg, M, van Veldhuisen, D, Kellis, M, Krijthe, B, Franco, O, Hofman, A, Kors, J, Uitterlinden, A, Witteman, J, Kedenko, L, Lamina, C, Oostra, B, Abecasis, G, Lakatta, E, Mulas, A, Orrú, M, Schlessinger, D, Uda, M, Markus, M, Völker, U, Snieder, H, Spector, T, Arnlöv, J, Lind, L, Sundström, J, Syvänen, A, Kivimaki, M, Kähönen, M, Mononen, N, Raitakari, O, Viikari, J, Adamkova, V, Kiechl, S, Brion, M, Nicolaides, A, Paulweber, B, Haerting, J, Dominiczak, A, Nyberg, F, Whincup, P, Hingorani, A, Schott, J, Bezzina, C, Ingelsson, E, Ferrucci, L, Gasparini, P, Wilson, J, Rudan, I, Franke, A, Mühleisen, T, Pramstaller, P, Lehtimäki, T, Paterson, A, Parsa, A, Liu, Y, van Duijn, C, Siscovick, D, Gudnason, V, Jamshidi, Y, Salomaa, V, Felix, S, Sanna, S, Ritchie, M, Stricker, B, Stefansson, K, Boyer, L, Cappola, T, Olsen, J, Lage, K, Schwartz, P, Kääb, S, Chakravarti, A, Ackerman, M, Pfeufer, A, de Bakker, P, Newton-Cheh, C, Arking, DE, Pulit, SL, Munroe, PB, Rossin, EJ, Johnson, AD, Gudbjartsson, DF, Noseworthy, PA, Tarasov, KV, Lahtinen, AM, Nolte, IM, Smith, AV, Bis, JC, Newhouse, SJ, Evans, DS, Post, WS, Lyytikäinen, LP, Hicks, AA, Tester, DJ, Morris, RW, Naluai, AT, Panayiotou, AG, Hubacek, JA, Kumar, RD, Harris, TB, Launer, LJ, Shuldiner, AR, Bader, JS, Kao, WH, Strait, JB, Macfarlane, PW, Caulfield, MJ, Samani, NJ, Smith, JG, Greiser, KH, Heckbert, SR, Psaty, BM, Rotter, JI, Wright, AF, Daly, MJ, Arnar, DO, Denny, JC, Roden, DM, Zuvich, RL, Plump, AS, Larson, MG, O'Donnell, CJ, D'Adamo, AP, Cummings, SR, Nalls, MA, Kontula, KK, Jöckel, KH, Nöthen, MM, Loos, RJ, Thelle, DS, Sinner, MF, de Boer, RA, van der Vleuten, PA, Beckmann, BM, Wilde, AA, Behr, ER, Giudicessi, JR, Hamilton, RM, Scherer, SW, Moravec, CE, Greco, MFD, O'Connell, JR, Lee, WK, Watt, GC, Wild, SH, El Mokhtari, NE, Asselbergs, FW, van den Berg, MP, van Veldhuisen, DJ, Krijthe, BP, Franco, OH, Kors, JA, Uitterlinden, AG, Witteman, JC, Oostra, BA, Abecasis, GR, Lakatta, EG, Markus, MR, Spector, TD, Syvänen, AC, Raitakari, OT, Viikari, JS, Nicolaides, AN, Dominiczak, AF, Whincup, PH, Hingorani, AD, Schott, JJ, Bezzina, CR, Wilson, JF, Mühleisen, TW, Pramstaller, PP, Lehtimäki, TJ, Paterson, AD, van Duijn, CM, Siscovick, DS, Felix, SB, Ritchie, MD, Stricker, BH, Boyer, LA, Cappola, TP, Olsen, JV, Schwartz, PJ, Ackerman, MJ, de Bakker, PI, Arking, D, Pulit, S, Crotti, L, van der Harst, P, Munroe, P, Koopmann, T, Sotoodehnia, N, Rossin, E, Morley, M, Wang, X, Johnson, A, Lundby, A, Gudbjartsson, D, Noseworthy, P, Eijgelsheim, M, Bradford, Y, Tarasov, K, Dörr, M, Müller-Nurasyid, M, Lahtinen, A, Nolte, I, Smith, A, Bis, J, Isaacs, A, Newhouse, S, Evans, D, Post, W, Waggott, D, Lyytikäinen, L, Hicks, A, Eisele, L, Ellinghaus, D, Hayward, C, Navarro, P, Ulivi, S, Tanaka, T, Tester, D, Chatel, S, Gustafsson, S, Kumari, M, Morris, R, Naluai, A, Padmanabhan, S, Kluttig, A, Strohmer, B, Panayiotou, A, Torres, M, Knoflach, M, Hubacek, J, Slowikowski, K, Raychaudhuri, S, Kumar, R, Harris, T, Launer, L, Shuldiner, A, Alonso, A, Bader, J, Ehret, G, Huang, H, Kao, W, Strait, J, Macfarlane, P, Brown, M, Caulfield, M, Samani, N, Kronenberg, F, Willeit, J, Smith, J, Greiser, K, Meyer Zu Schwabedissen, H, Werdan, K, Carella, M, Zelante, L, Heckbert, S, Psaty, B, Rotter, J, Kolcic, I, Polašek, O, Wright, A, Griffin, M, Daly, M, Arnar, D, Hólm, H, Thorsteinsdottir, U, Denny, J, Roden, D, Zuvich, R, Emilsson, V, Plump, A, Larson, M, O'Donnell, C, Yin, X, Bobbo, M, D'Adamo, A, Iorio, A, Sinagra, G, Carracedo, A, Cummings, S, Nalls, M, Jula, A, Kontula, K, Marjamaa, A, Oikarinen, L, Perola, M, Porthan, K, Erbel, R, Hoffmann, P, Jöckel, K, Kälsch, H, Nöthen, M, den Hoed, M, Loos, R, Thelle, D, Gieger, C, Meitinger, T, Perz, S, Peters, A, Prucha, H, Sinner, M, Waldenberger, M, de Boer, R, Franke, L, van der Vleuten, P, Beckmann, B, Martens, E, Bardai, A, Hofman, N, Wilde, A, Behr, E, Dalageorgou, C, Giudicessi, J, Medeiros-Domingo, A, Kyndt, F, Probst, V, Ghidoni, A, Insolia, R, Hamilton, R, Scherer, S, Brandimarto, J, Margulies, K, Moravec, C, Greco, M, Fuchsberger, C, O'Connell, J, Lee, W, Watt, G, Campbell, H, Wild, S, El Mokhtari, N, Frey, N, Asselbergs, F, Mateo Leach, I, Navis, G, van den Berg, M, van Veldhuisen, D, Kellis, M, Krijthe, B, Franco, O, Hofman, A, Kors, J, Uitterlinden, A, Witteman, J, Kedenko, L, Lamina, C, Oostra, B, Abecasis, G, Lakatta, E, Mulas, A, Orrú, M, Schlessinger, D, Uda, M, Markus, M, Völker, U, Snieder, H, Spector, T, Arnlöv, J, Lind, L, Sundström, J, Syvänen, A, Kivimaki, M, Kähönen, M, Mononen, N, Raitakari, O, Viikari, J, Adamkova, V, Kiechl, S, Brion, M, Nicolaides, A, Paulweber, B, Haerting, J, Dominiczak, A, Nyberg, F, Whincup, P, Hingorani, A, Schott, J, Bezzina, C, Ingelsson, E, Ferrucci, L, Gasparini, P, Wilson, J, Rudan, I, Franke, A, Mühleisen, T, Pramstaller, P, Lehtimäki, T, Paterson, A, Parsa, A, Liu, Y, van Duijn, C, Siscovick, D, Gudnason, V, Jamshidi, Y, Salomaa, V, Felix, S, Sanna, S, Ritchie, M, Stricker, B, Stefansson, K, Boyer, L, Cappola, T, Olsen, J, Lage, K, Schwartz, P, Kääb, S, Chakravarti, A, Ackerman, M, Pfeufer, A, de Bakker, P, Newton-Cheh, C, Arking, DE, Pulit, SL, Munroe, PB, Rossin, EJ, Johnson, AD, Gudbjartsson, DF, Noseworthy, PA, Tarasov, KV, Lahtinen, AM, Nolte, IM, Smith, AV, Bis, JC, Newhouse, SJ, Evans, DS, Post, WS, Lyytikäinen, LP, Hicks, AA, Tester, DJ, Morris, RW, Naluai, AT, Panayiotou, AG, Hubacek, JA, Kumar, RD, Harris, TB, Launer, LJ, Shuldiner, AR, Bader, JS, Kao, WH, Strait, JB, Macfarlane, PW, Caulfield, MJ, Samani, NJ, Smith, JG, Greiser, KH, Heckbert, SR, Psaty, BM, Rotter, JI, Wright, AF, Daly, MJ, Arnar, DO, Denny, JC, Roden, DM, Zuvich, RL, Plump, AS, Larson, MG, O'Donnell, CJ, D'Adamo, AP, Cummings, SR, Nalls, MA, Kontula, KK, Jöckel, KH, Nöthen, MM, Loos, RJ, Thelle, DS, Sinner, MF, de Boer, RA, van der Vleuten, PA, Beckmann, BM, Wilde, AA, Behr, ER, Giudicessi, JR, Hamilton, RM, Scherer, SW, Moravec, CE, Greco, MFD, O'Connell, JR, Lee, WK, Watt, GC, Wild, SH, El Mokhtari, NE, Asselbergs, FW, van den Berg, MP, van Veldhuisen, DJ, Krijthe, BP, Franco, OH, Kors, JA, Uitterlinden, AG, Witteman, JC, Oostra, BA, Abecasis, GR, Lakatta, EG, Markus, MR, Spector, TD, Syvänen, AC, Raitakari, OT, Viikari, JS, Nicolaides, AN, Dominiczak, AF, Whincup, PH, Hingorani, AD, Schott, JJ, Bezzina, CR, Wilson, JF, Mühleisen, TW, Pramstaller, PP, Lehtimäki, TJ, Paterson, AD, van Duijn, CM, Siscovick, DS, Felix, SB, Ritchie, MD, Stricker, BH, Boyer, LA, Cappola, TP, Olsen, JV, Schwartz, PJ, Ackerman, MJ, and de Bakker, PI
- 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
35. Motherhood and oxytocin receptor genetic variation are associated with selective changes in electrocortical responses to infant facial expressions
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Peltola, M, Yrttiaho, S, Puura, K, Proverbio, A, Mononen, N, Lehtimäki, T, Leppänen, J, Peltola, MJ, PROVERBIO, ALICE MADO, Leppänen, JM, Peltola, M, Yrttiaho, S, Puura, K, Proverbio, A, Mononen, N, Lehtimäki, T, Leppänen, J, Peltola, MJ, PROVERBIO, ALICE MADO, and Leppänen, JM
- Abstract
Recent studies suggest that parental caregiving is associated with adaptive changes in neurocognitive responses to emotional cues and oxytocin function, possibly reflecting the increased need of parents to monitor infants' emotional states. In the current study, we investigated whether the changes associated with motherhood and oxytocin receptor genetic variation rs53576 are specific to the processing of infant cues as opposed to a more general increase in responsiveness to emotional cues. We measured event-related brain potentials (ERPs) and behavioral recognition responses from mothers of young infants (n = 48) and nulliparous females (n = 46) to infant and adult faces displaying strong and mild intensity emotional expressions. Mothers and GG allele carriers of the OXTR gene showed an early latency (~100 ms) differential frontal ERP response to strong intensity facial expressions, and mothers also showed modulation of the posterior EPN waveform by negative valence. The early frontal ERP modulation was associated with faster emotion recognition performance across participants. Most importantly, these effects were highly specific to infant facial expressions. The results point to a dissociable neurocognitive system that is involved in monitoring infants' emotional cues and may be important in supporting parental caregiving in humans. © 2014 American Psychological Association.
- Published
- 2014
36. Two percent of Finnish prostate cancer patients have a germ-line mutation in the hormone-binding domain of the androgen receptor gene
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Mononen N, Syrjäkoski K, Matikainen M, Tl, Tammela, Johanna Schleutker, Op, Kallioniemi, Trapman J, and Pa, Koivisto
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Male ,Binding Sites ,Receptors, Androgen ,Humans ,Prostatic Neoplasms ,Female ,Germ-Line Mutation ,Hormones ,Protein Structure, Tertiary ,Repetitive Sequences, Nucleic Acid - Abstract
Mutations of the androgen receptor (AR) gene have been reported in prostate cancer, usually from tumor tissue specimens from late-stage, androgen-independent cancer. Occasionally, germ-line mutations have been found, but a link between AR mutations and predisposition to human prostate cancer has not been firmly established. Recently, two independent studies reported the same germ-line mutation at codon 726 in exon E (CGC to CTC) in two apparently unrelated Finnish prostate cancer patients. This arginine to leucine substitution was reported to alter the transactivational specificity of the AR protein. In the present study, the R726L mutation was analyzed by allele-specific oligohybridization in DNA specimens from 418 consecutive prostate cancer patients who reported a negative family history (sporadic group) and from 106 patients with a positive family history (hereditary group). The population frequency of the R726L mutation in blood donors was 3 of 900 (0.33%). In contrast, eight (1.91%) mutations (odds ratio = 5.8; P = 0.006) were found in the sporadic group, and two (1.89%) mutations were found in the hereditary group (odds ratio = 5.8; P = 0.09). Suggestive evidence of the segregation of the mutation with prostate cancer was seen in these two families. The present study indicates that the R726L substitution in the AR may confer an up to 6-fold increased risk of prostate cancer and may contribute to cancer development in up to 2% of Finnish prostate cancer patients. These results warrant additional large-scale studies of the significance of rare mutations and polymorphisms in candidate genes along the androgen signaling pathway as risk factors for prostate cancer.
- Published
- 2000
37. MS194 THE INFLUENCE OF APOLIPOPROTEIN E GENETIC VARIANTS ON SERUM LIPIDS AND INSULIN RESISTANCE IN TARF STUDY
- Author
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Komurcu Bayrak, E., primary, Onat, A., additional, Yuzbasiogullari, B., additional, Mononen, N., additional, Laaksonen, R., additional, Hergenc, G., additional, Humphries, S.E., additional, Lehtimäki, T., additional, and Erginel-Unaltuna, N., additional
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- 2010
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38. CRP GENE POLYMORPHISMS ARE INVOLVED IN THE REGULATION OF PLASMA CRP CONCENTRATIONS IN TURKISH POPULATION: TURKISH ADULT RISK FACTOR STUDY
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Komurcu-Bayrak, E., primary, Ozsait, B., additional, Mononen, N., additional, Laaksonen, R., additional, Onat, A., additional, Hergenc, G., additional, Lehtimaki, T., additional, and Erginel-Unaltuna, N., additional
- Published
- 2008
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39. USF1 GENE IS INVOLVED IN THE REGULATION OF HUMAN LONGEVITY
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Ozsait, B., primary, Komurcu-Bayrak, E., additional, Jylha, M., additional, Perola, M., additional, Kristiansson, K., additional, Mononen, N., additional, Hurme, M., additional, Laaksonen, R., additional, Hervonen, A., additional, Erginel-Unaltuna, N., additional, Karhunen, P., additional, and Lehtimaki, T., additional
- Published
- 2008
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- View/download PDF
40. PO5-134 ANDROGEN RECEPTOR CAG POLYMORPHISM AND CORONARY ARTERY DISEASE
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Mononen, N., primary, Kähönen, M., additional, Hyytinen, E., additional, Nieminen, T., additional, Niemelä, K., additional, Karhunen, P.J., additional, Goebeler, S., additional, Koivisto, P., additional, and Lehtimäki, T., additional
- Published
- 2007
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- View/download PDF
41. 849 The role of CHEK2 and MSR1 genes in prostate cancer predisposition in Finland
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Matikainen, M., primary, Seppälä, E., additional, Ikonen, T., additional, Autio, V., additional, Mononen, N., additional, Rökman, A., additional, Tammela, T., additional, and Schleutker, J., additional
- Published
- 2004
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42. CHEK2 variants associate with hereditary prostate cancer
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Seppälä, E H, primary, Ikonen, T, additional, Mononen, N, additional, Autio, V, additional, Rökman, A, additional, Matikainen, M P, additional, Tammela, T L J, additional, and Schleutker, J, additional
- Published
- 2003
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43. A missense substitution A49T in the steroid 5-alpha-reductase gene (SRD5A2) is not associated with prostate cancer in Finland
- Author
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Mononen, N, primary, Ikonen, T, additional, Syrjäkoski, K, additional, Matikainen, M, additional, Schleutker, J, additional, Tammela, T L J, additional, Koivisto, P A, additional, and Kallioniemi, O P, additional
- Published
- 2001
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44. Association of E-cadherin germ-line alterations with prostate cancer
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Ikonen T, Matikainen M, Mononen N, Er, Hyytinen, Hj, Helin, Tommola S, Tl, Tammela, Pukkala E, Johanna Schleutker, Op, Kallioniemi, and Pa, Koivisto
- Subjects
Aged, 80 and over ,Family Health ,Male ,DNA Mutational Analysis ,Mutation, Missense ,Nuclear Proteins ,Prostatic Neoplasms ,DNA, Neoplasm ,Cadherins ,Colorectal Neoplasms, Hereditary Nonpolyposis ,Neoplasm Proteins ,Pedigree ,Stomach Neoplasms ,Mutation ,Humans ,Female ,Genetic Testing ,Carrier Proteins ,MutL Protein Homolog 1 ,Germ-Line Mutation ,Adaptor Proteins, Signal Transducing ,Aged - Abstract
In our recent cancer registry-based study, the incidence of gastric carcinoma was increased up to 5-fold in male relatives of early-onset prostate cancer (PCA) patients. This association may reflect the influence of genetic factors predisposing individuals to both tumor types. Germ-line mutations of the CDH1 gene at 16q have recently been associated with familial gastric cancer. Furthermore, two genome-wide linkage studies of PCA recently reported positivity at 16q. We therefore identified families and individual patients with both gastric and PCA and investigated whether the CDH1 gene mutations were involved in cancer predisposition in these cases. Fifteen of the 180 Finnish hereditary PCA families (8.3%) had one or more gastric cancer cases. No truncating or splice site CDH1 mutations were identified by PCR single-strand conformational polymorphism in these families or in eight individual patients who had both prostate and gastric cancer. However, a novel S270A missense mutation in exon 6 of the CDH1 gene was seen in a single family with four prostate and two gastric cancers. A large-scale population-based survey indicated a higher prevalence of S270A among both familial PCA cases (3.3%; n = 120; P = 0.01) and unselected PCA patients (1.5%; n = 472; P = 0.12) as compared with blood donors serving as population controls (0.5%; n = 923). We conclude that individual rare mutations and polymorphisms in the CDH1 gene, such as S270A, may contribute to the onset of PCA and warrant further investigations in other populations. However, the CDH1 gene does not appear to explain the link between prostate and gastric cancer.
45. ELAC2/HPC2 involvement in hereditary and sporadic prostate cancer
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Rökman A, Ikonen T, Mononen N, Autio V, Mp, Matikainen, Pa, Koivisto, Tl, Tammela, Op, Kallioniemi, and Johanna Schleutker
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Aged, 80 and over ,Male ,Mutation, Missense ,Genetic Variation ,Prostatic Neoplasms ,DNA ,DNA, Neoplasm ,Exons ,Middle Aged ,Neoplasm Proteins ,Humans ,Genetic Predisposition to Disease ,Finland ,Polymorphism, Restriction Fragment Length ,Polymorphism, Single-Stranded Conformational ,Aged - Abstract
The ELAC2/HPC2 gene at 17p11 is the first candidate gene identified for human prostate cancer (PRCA) based on linkage analysis and positional cloning (S. V. Tavtigian et al. Nat. Genet., 27:172-180, 2001). A truncating mutation was found in one hereditary prostate cancer (HPC) family, whereas two missense variants, Ser217Leu and Ala541Thr, were reported to be associated with increased PRCA risk in the general population. Here, we screened for mutations of the ELAC2/HPC2 gene in 66 Finnish HPC families. Several sequence variants, including a new exonic variant (Glu622Val) were found, but none of the mutations were truncating. We then analyzed the frequency of the three found missense variants in 1365 individuals, including hereditary (n = 107) and unselected (n = 467) PRCA, benign prostatic hyperplasia (n = 223), and population controls (568 healthy male blood donors). Ser217Leu and Ala541Thr variants carried no significantly elevated risk for HPC or PRCA, although the latter variant was associated with benign prostatic hyperplasia. The previously undescribed Glu622Val variant had a 1.0% population prevalence, but a significantly higher frequency in PRCA cases (3.0% odds ratio, 2.94; 95% confidence interval, 1.05-8.23). We conclude that ELAC2/HPC2 truncating mutations are rare in HPC, but that rare variants of the ELAC2/HPC2 require additional study as risk factors for PRCA in the general population.
46. The Helsinki University of Technology/Ylinen Electronics airborne L-band interferometric radiometer
- Author
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Rautiainen, K., primary, Butora, R., additional, Auer, T., additional, Mononen, N., additional, Salminen, J., additional, Tauriainen, S., additional, Hallikainen, M., additional, Uusitalo, J., additional, and Jukkala, P., additional
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47. The Helsinki University of Technology/Ylinen Electronics airborne L-band interferometric radiometer.
- Author
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Rautiainen, K., Butora, R., Auer, T., Mononen, N., Salminen, J., Tauriainen, S., Hallikainen, M., Uusitalo, J., and Jukkala, P.
- Published
- 2000
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48. Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction
- Author
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Dennis O. Mook-Kanamori, Yalda Jamshidi, Peter K. Joshi, Seung Hoan Choi, Henry J. Lin, Rebecca D. Jackson, Alison D. Murray, May E. Montasser, Veikko Salomaa, Charles Kooperberg, Moritz F. Sinner, Gianfranco Sinagra, Luisa Foco, James G. Wilson, Johan Sundström, Kathleen A. Ryan, Eric A. Whitsel, Bruno H. Stricker, Sandosh Padmanabhan, Christopher Newton-Cheh, Ozren Polasek, Unnur Thorsteinsdottir, Niek Verweij, Pier D. Lambiase, Nathan R. Tucker, Stefan Kääb, Jun Ding, Stefan Weiss, Daniel F. Gudbjartsson, David Conen, Lars Lind, Ivana Kolcic, Lu-Chen Weng, J. Wouter Jukema, Kirill V. Tarasov, Xiuqing Guo, Stella Trompet, Patricia B. Munroe, Albert V. Smith, Elsayed Z. Soliman, Andrew Tinker, Antti Jula, J. Gustav Smith, Alexander P. Reiner, Sébastien Thériault, Kathryn L. Lunetta, Vilmundur Gudnason, Mika Kähönen, Massimo Mangino, Raymond Noordam, Joshua C. Bis, Alan R. Shuldiner, Tim D. Spector, Borbala Mifsud, Stefan van Duijvenboden, Jeffrey R. O'Connell, Emelia J. Benjamin, M. Benjamin Shoemaker, Stephan B. Felix, Peter W. Macfarlane, Lorenz Risch, Uwe Völker, Stephanie M. Gogarten, Maria Fernanda Lima-Costa, Julia Ramirez, Morten S. Olesen, Konstantin Strauch, Annette Peters, Aaron Isaacs, Steven A. Lubitz, Eric Boerwinkle, Carolina Roselli, James H. Cartwright, Nathalia M. Araujo, Ruth J. F. Loos, Diane Fatkin, Harry Campbell, Blair H. Smith, Thomas Meitinger, André G. Uitterlinden, Paul L. Huang, Tamara B. Harris, Kathleen F. Kerr, David J. Porteous, Martina Müller-Nurasyid, Francesco Cucca, Michiel Rienstra, Davíð O. Arnar, Amanda A. Seyerle, Caroline Hayward, M. Abdullah Said, Catriona L. K. Barnes, Kent D. Taylor, Nona Sotoodehnia, Nina Mononen, Dan M. Roden, Jonathan Marten, Terho Lehtimäki, Dan E. Arking, Anna F. Dominiczak, Jan A. Kors, Olli T. Raitakari, Igor Rudan, Yordi J. van de Vegte, Christopher P. Nelson, Erik Ingelsson, Ulrike Peters, Girish N. Nadkarni, Eduardo Tarazona-Santos, Edward G. Lakatta, Nina Hutri-Kähönen, Bruce M. Psaty, Patrick T. Ellinor, Christian Fuchsberger, Katharina Schramm, Amelia W. Hall, M. Yldau van der Ende, Alvaro Alonso, James F. Wilson, Sheila Ulivi, Rosa B. Thorolfsdottir, Stefanie Aeschbacher, Mary L. Biggs, Marten E. van den Berg, Nilesh J. Samani, Thibaud Boutin, Vilmantas Giedraitis, Honghuang Lin, Kjell Nikus, Helen R. Warren, Arie C. Maan, James J. Cranley, Adolfo Correa, Martin Gögele, Ian Ford, Katri Sääksjärvi, Georg Ehret, Michele Orini, Susan R. Heckbert, Cecilia M. Lindgren, Jie Yao, Maria Pina Concas, Pim van der Harst, Ioanna Ntalla, Jeffrey Haessler, Jerome I. Rotter, Pashupati P. Mishra, Michael J. Cutler, Erwin P. Bottinger, Cornelia M. van Duijn, Jennifer A. Brody, Paolo Gasparini, Lenore J. Launer, Andrew P. Morris, Renée de Mutsert, Aki S. Havulinna, James P. Cook, Hilma Holm, Patrick Sulem, Alessandro De Grandi, Cristian Pattaro, Gardar Sveinbjornsson, Antonio Luiz Pinho Ribeiro, Mark J. Caulfield, Gudmar Thorleifsson, Marcus Dörr, Muhammad B. Riaz, Peter P. Pramstaller, Yong Qian, Anubha Mahajan, Cathy C. Laurie, Kenneth Rice, Mark Chaffin, Kari Stefansson, Andrew A. Hicks, Solmaz Assa, Hao Mei, Leo-Pekka Lyytikäinen, Fabiola Del Greco M, Renan P. Souza, Michael Preuss, Adrienne M. Stilp, Barry London, Melanie Waldenberger, Christy L. Avery, Daniel Levy, Michael R. Barnes, Medical Informatics, Epidemiology, Internal Medicine, Weng, Lu-Chen [0000-0003-1475-4930], Hall, Amelia Weber [0000-0002-7915-0313], Tucker, Nathan R [0000-0002-5071-4218], Chaffin, Mark D [0000-0002-1234-5562], Roselli, Carolina [0000-0001-5267-6756], Barnes, Michael R [0000-0001-9097-7381], Mifsud, Borbala [0000-0003-3429-3094], Hayward, Caroline [0000-0002-9405-9550], Concas, Maria Pina [0000-0003-3598-2537], Boutin, Thibaud [0000-0003-4754-1675], Kolcic, Ivana [0000-0001-7918-6052], Rudan, Igor [0000-0001-6993-6884], Souza, Renan P [0000-0002-9479-4432], Giedraitis, Vilmantas [0000-0003-3423-2021], Ingelsson, Erik [0000-0003-2256-6972], Mahajan, Anubha [0000-0001-5585-3420], Morris, Andrew P [0000-0002-6805-6014], Hicks, Andrew A [0000-0001-6320-0411], Sundström, Johan [0000-0003-2247-8454], Nelson, Christopher P [0000-0001-8025-2897], Riaz, Muhammad B [0000-0002-5512-1745], Sinagra, Gianfranco [0000-0003-2700-8478], Mishra, Pashupati P [0000-0001-5177-3431], Caulfield, Mark J [0000-0001-9295-3594], Dominiczak, Anna [0000-0003-4913-3608], Risch, Lorenz [0000-0003-2692-6699], Joshi, Peter K [0000-0002-6361-5059], Wilson, James F [0000-0001-5751-9178], Isaacs, Aaron [0000-0001-5037-4834], van Duijn, Cornelia M [0000-0002-2374-9204], Gudnason, Vilmundur [0000-0001-5696-0084], Smith, Albert V [0000-0003-1942-5845], Loos, Ruth JF [0000-0002-8532-5087], Preuss, Michael H [0000-0001-5266-8465], Correa, Adolfo [0000-0002-9501-600X], Müller-Nurasyid, Martina [0000-0003-3793-5910], Waldenberger, Melanie [0000-0003-0583-5093], Mangino, Massimo [0000-0002-2167-7470], Rienstra, Michiel [0000-0002-2581-070X], van der Harst, Pim [0000-0002-2713-686X], Verweij, Niek [0000-0002-4303-7685], Fatkin, Diane [0000-0002-9010-9856], Brody, Jennifer A [0000-0001-8509-148X], Rice, Kenneth [0000-0002-3071-7278], Pattaro, Cristian [0000-0002-4119-0109], Wouter Jukema, J [0000-0002-3246-8359], Weiss, Stefan [0000-0002-3553-4315], Havulinna, Aki S [0000-0002-4787-8959], Sääksjärvi, Katri [0000-0002-5061-4911], Salomaa, Veikko [0000-0001-7563-5324], Rotter, Jerome I [0000-0001-7191-1723], Taylor, Kent D [0000-0002-2756-4370], Lakatta, Edward G [0000-0002-4772-0035], Lin, Honghuang [0000-0003-3043-3942], Lunetta, Kathryn L [0000-0002-9268-810X], Murray, Alison D [0000-0003-4915-4847], Porteous, David J [0000-0003-1249-6106], Smith, Blair H [0000-0002-5362-9430], Uitterlinden, André [0000-0002-7276-3387], Peters, Ulrike [0000-0001-5666-9318], Alonso, Alvaro [0000-0002-2225-8323], Ehret, Georg B [0000-0002-5730-0675], Soliman, Elsayed Z [0000-0001-5632-8150], Gogarten, Stephanie M [0000-0002-7231-9745], Kerr, Kathleen F [0000-0002-6438-9583], Abdullah Said, M [0000-0003-2920-7745], Orini, Michele [0000-0001-5773-0344], Ramirez, Julia [0000-0003-4130-5866], Van Duijvenboden, Stefan [0000-0001-8897-558X], Gudbjartsson, Daniel F [0000-0002-5222-9857], Sulem, Patrick [0000-0001-7123-6123], Thorolfsdottir, Rosa B [0000-0001-7475-0398], Benjamin, Emelia J [0000-0003-4076-2336], Stefansson, Kari [0000-0003-1676-864X], Ellinor, Patrick T [0000-0002-2067-0533], Jamshidi, Yalda [0000-0003-0151-6482], Lubitz, Steven A [0000-0002-9599-4866], Munroe, Patricia B [0000-0002-4176-2947], Apollo - University of Cambridge Repository, Medicum, Institute for Molecular Medicine Finland, Complex Disease Genetics, Helsinki Institute of Life Science HiLIFE, University of Helsinki, Cardiovascular Centre (CVC), Ntalla, I., Weng, L. -C., Cartwright, J. H., Hall, A. W., Sveinbjornsson, G., Tucker, N. R., Choi, S. H., Chaffin, M. D., Roselli, C., Barnes, M. R., Mifsud, B., Warren, H. R., Hayward, C., Marten, J., Cranley, J. J., Concas, M. P., Gasparini, P., Boutin, T., Kolcic, I., Polasek, O., Rudan, I., Araujo, N. M., Lima-Costa, M. F., Ribeiro, A. L. P., Souza, R. P., Tarazona-Santos, E., Giedraitis, V., Ingelsson, E., Mahajan, A., Morris, A. P., Del Greco M, F., Foco, L., Gogele, M., Hicks, A. A., Cook, J. P., Lind, L., Lindgren, C. M., Sundstrom, J., Nelson, C. P., Riaz, M. B., Samani, N. J., Sinagra, G., Ulivi, S., Kahonen, M., Mishra, P. P., Mononen, N., Nikus, K., Caulfield, M. J., Dominiczak, A., Padmanabhan, S., Montasser, M. E., O'Connell, J. R., Ryan, K., Shuldiner, A. R., Aeschbacher, S., Conen, D., Risch, L., Theriault, S., Hutri-Kahonen, N., Lehtimaki, T., Lyytikainen, L. -P., Raitakari, O. T., Barnes, C. L. K., Campbell, H., Joshi, P. K., Wilson, J. F., Isaacs, A., Kors, J. A., van Duijn, C. M., Huang, P. L., Gudnason, V., Harris, T. B., Launer, L. J., Smith, A. V., Bottinger, E. P., Loos, R. J. F., Nadkarni, G. N., Preuss, M. H., Correa, A., Mei, H., Wilson, J., Meitinger, T., Muller-Nurasyid, M., Peters, A., Waldenberger, M., Mangino, M., Spector, T. D., Rienstra, M., van de Vegte, Y. J., van der Harst, P., Verweij, N., Kaab, S., Schramm, K., Sinner, M. F., Strauch, K., Cutler, M. J., Fatkin, D., London, B., Olesen, M., Roden, D. M., Benjamin Shoemaker, M., Gustav Smith, J., Biggs, M. L., Bis, J. C., Brody, J. A., Psaty, B. M., Rice, K., Sotoodehnia, N., De Grandi, A., Fuchsberger, C., Pattaro, C., Pramstaller, P. P., Ford, I., Wouter Jukema, J., Macfarlane, P. W., Trompet, S., Dorr, M., Felix, S. B., Volker, U., Weiss, S., Havulinna, A. S., Jula, A., Saaksjarvi, K., Salomaa, V., Guo, X., Heckbert, S. R., Lin, H. J., Rotter, J. I., Taylor, K. D., Yao, J., de Mutsert, R., Maan, A. C., Mook-Kanamori, D. O., Noordam, R., Cucca, F., Ding, J., Lakatta, E. G., Qian, Y., Tarasov, K. V., Levy, D., Lin, H., Newton-Cheh, C. H., Lunetta, K. L., Murray, A. D., Porteous, D. J., Smith, B. H., Stricker, B. H., Uitterlinden, A., van den Berg, M. E., Haessler, J., Jackson, R. D., Kooperberg, C., Peters, U., Reiner, A. P., Whitsel, E. A., Alonso, A., Arking, D. E., Boerwinkle, E., Ehret, G. B., Soliman, E. Z., Avery, C. L., Gogarten, S. M., Kerr, K. F., Laurie, C. C., Seyerle, A. A., Stilp, A., Assa, S., Abdullah Said, M., Yldau van der Ende, M., Lambiase, P. D., Orini, M., Ramirez, J., Van Duijvenboden, S., Arnar, D. O., Gudbjartsson, D. F., Holm, H., Sulem, P., Thorleifsson, G., Thorolfsdottir, R. B., Thorsteinsdottir, U., Benjamin, E. J., Tinker, A., Stefansson, K., Ellinor, P. T., Jamshidi, Y., Lubitz, S. A., Munroe, P. B., Fysiologie, RS: FHML MaCSBio, RS: Carim - B01 Blood proteins & engineering, Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Verkfræði- og náttúruvísindasvið (HÍ), School of Engineering and Natural Sciences (UI), Háskóli Íslands, and University of Iceland
- Subjects
0301 basic medicine ,Male ,Multifactorial Inheritance ,General Physics and Astronomy ,Gene Expression ,Genome-wide association study ,030204 cardiovascular system & hematology ,Arrhythmias ,Genome-wide association studies ,CALCINEURIN ,Electrocardiography ,0302 clinical medicine ,Cardiovascular Disease ,Multi-ancestry GWAS ,ELEMENTS ,Medicine ,Cardiac and Cardiovascular Systems ,Blóðrásarsjúkdómar ,lcsh:Science ,RISK ,DECREASE ,education.field_of_study ,Multidisciplinary ,Kardiologi ,medicine.diagnostic_test ,1184 Genetics, developmental biology, physiology ,Atrial fibrillation ,3142 Public health care science, environmental and occupational health ,3. Good health ,Endophenotype ,Arrhythmias, Cardiac ,Cardiovascular Diseases ,Endophenotypes ,Female ,Genetic Loci ,Genetic Predisposition to Disease ,Genetic Variation ,Genome-Wide Association Study ,Humans ,Quantitative Trait Loci ,cardiovascular system ,Cardiology ,medicine.symptom ,Erfðarannsóknir ,Cardiac ,Medical Genetics ,Human ,Bradycardia ,medicine.medical_specialty ,Science ,GENOME-WIDE ASSOCIATION ,ATRIAL-FIBRILLATION ,MUTATIONS ,DURATION ,CARDIOMYOPATHY ,BRADYCARDIA ,Population ,Article ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Internal medicine ,Cardiac conduction ,PR interval ,education ,Medicinsk genetik ,business.industry ,Cardiovascular genetics ,General Chemistry ,Arfgengi ,medicine.disease ,030104 developmental biology ,lcsh:Q ,business - Abstract
Publisher's version (útgefin grein), 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 conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease., We provide all investigator and study-specific acknowledgements in Supplementary Note 1, and funding sources in Supplementary Note 2.
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- 2020
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49. A catalog of genetic loci associated with kidney function from analyses of a million individuals
- Author
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Wuttke, Matthias, Li, Yong, Li, Man, Sieber, Karsten B., Feitosa, Mary F., Gorski, Mathias, Tin, Adrienne, Wang, Lihua, Chu, Audrey Y., Hoppmann, Anselm, Kirsten, Holger, Giri, Ayush, Chai, Jin-Fang, Sveinbjornsson, Gardar, Tayo, Bamidele O., Nutile, Teresa, Fuchsberger, Christian, Marten, Jonathan, Cocca, Massimiliano, Ghasemi, Sahar, Xu, Yizhe, Horn, Katrin, Noce, Damia, van der Most, Peter J., Sedaghat, Sanaz, Yu, Zhi, Akiyama, Masato, Afaq, Saima, Ahluwalia, Tarunveer S., Almgren, Peter, Amin, Najaf, Ärnlöv, Johan, Bakker, Stephan J. L., Bansal, Nisha, Baptista, Daniela, Bergmann, Sven, Biggs, Mary L., Biino, Ginevra, Boehnke, Michael, Boerwinkle, Eric, Boissel, Mathilde, Bottinger, Erwin P., Boutin, Thibaud S., Brenner, Hermann, Brumat, Marco, Burkhardt, Ralph, Butterworth, Adam S., Campana, Eric, Campbell, Archie, Campbell, Harry, Canouil, Mickaël, Carroll, Robert J., Catamo, Eulalia, Chambers, John C., Chee, Miao-Ling, Chee, Miao-Li, Chen, Xu, Cheng, Ching-Yu, Cheng, Yurong, Christensen, Kaare, Cifkova, Renata, Ciullo, Marina, Pina Concas, Maria, Cook, James P., Coresh, Josef, Corre, Tanguy, Sala, Cinzia Felicita, Cusi, Daniele, Danesh, John, Daw, E. Warwick, de Borst, Martin H., De Grandi, Alessandro, de Mutsert, Renée, de Vries, Aiko P. J., Degenhardt, Frauke, Delgado, Graciela, Demirkan, Ayse, Di Angelantonio, Emanuele, Dittrich, Katalin, Divers, Jasmin, Dorajoo, Rajkumar, Eckardt, Kai-Uwe, Ehret, Georg, Elliott, Paul, Endlich, Karlhans, Evans, Michele K., Felix, Janine F., Foo, Valencia Hui Xian, Franco, Oscar H., Franke, Andre, Freedman, Barry I., Freitag-Wolf, Sandra, Friedlander, Yechiel, Froguel, Philippe, Gansevoort, Ron T., Gao, He, Gasparini, Paolo, Gaziano, J. Michael, Giedraitis, Vilmantas, Gieger, Christian, Girotto, Giorgia, Giulianini, Franco, Gögele, Martin, Gordon, Scott D., Gudbjartsson, Daniel F., Gudnason, Vilmundur, Haller, Toomas, Hamet, Pavel, Harris, Tamara B., Hartman, Catharina A., Hayward, Caroline, Hellwege, Jacklyn N., Heng, Chew-Kiat, Hickst, Andrew A., Hofer, Edith, Huang, Wei, Hutri-Kähönen, Nina, Hwang, Shih-Jen, ikram, M. Arfan, indridason, Olafur S., Ingelsson, Erik, ising, Marcus, Jaddoe, Vincent W. V., Jakobsdottir, Johanna, Jonas, Jost B, Joshi, Peter K., Shilpa Josyula, Navya, Jung, Bettina, Kähönen, Mika, Kamatani, Yoichiro, Kammerer, Candace M., Kanai, Masahiro, Kastarinen, Mika, Kerr, Shona M., Khor, Chiea-Chuen, Kiess, Wieland, Kleber, Marcus E., Koenig, Wolfgang, Kooner, Jaspal S., Körner, Antje, Kovacs, Peter, Kraja, Aldi T., Krajcoviechova, Alena, Kramer, Holly, Krämer, Bernhard K., Kronenberg, Florian, Kubo, Michiaki, Kühnel, Brigitte, Kuokkanen, Mikko, Kuusisto, Johanna, La Bianca, Martina, Laakso, Markku, Lange, Leslie A., Langefeld, Carl D., Jen-Mai Lee, Jeannette, Lehne, Benjamin, Lehtimäki, Terho, Lieb, Wolfgang, Cohort Study, Lifelines, Lim, Su-Chi, Lind, Lars, Lindgren, Cecilia M., Liu, Jun, Liu, Jianjun, Loeffler, Markus, Loos, Ruth J. F., Lucae, Susanne, Ann Lukas, Mary, Lyytikäinen, Leo-Pekka, Mägi, Reedik, Magnusson, Patrik K. E., Mahajan, Anubha, Martin, Nicholas G., Martins, Jade, März, Winfried, Mascalzoni, Deborah, Matsuda, Koichi, Christa Meisinger, Meitinger, Thomas, Melander, Olle, Metspalu, Andres, Mikaelsdottir, Evgenia K., Milaneschi, Yuri, Miliku, Kozeta, Mishra, Pashupati P., Veteran Program, V. A. Million, Mohlke, Karen L., Mononen, Nina, Montgomery, Grant W., Mook-Kanamori, Dennis O., Mychaleckyj, Josyf C., Nadkarni, Girish N, Nalls, Mike A., Nauck, Matthias, Nikus, Kjell, Ning, Boting, Nolte, ilja M., Noordam, Raymond, O’Connell, Jeffrey, O’Donoghue, Michelle L., Olafsson, Isleifur, Oldehinkel, Albertine J., Orho-Melander, Marju, Ouwehand, Willem H., Padmanabhan, Sandosh, Palmer, Nicholette D., Palsson, Runolfur, Penninx, Brenda W. J. H., Perls, Thomas, Perola, Markus, Pirastu, Mario, Pirastu, Nicola, Pistis, Giorgio, Podgornaia, Anna I., Polasek, Ozren, Ponte, Belen, Porteous, David J., Poulain, Tanja, Pramstaller, Peter P., Preuss, Michael H., Prins, Bram P., Province, Michael A., Rabelink, Ton J., Raffield, Laura M., Raitakari, Olli T., Reilly, Dermot F., Rettig, Rainer, Rheinberger, Myriam, Rice, Kenneth M., Ridker, Paul M., Rivadeneira, Fernando, Rizzi, Federica, Roberts, David J., Robino, Antonietta, Rossing, Peter, Rudan, Igor, Rueedi, Rico, Ruggiero, Daniela, Ryan, Kathleen A., Saba, Yasaman, Sabanayagam, Charumathi, Salomaa, Veikko, Salvi, Erika, Saum, Kai-Uwe, Schmidt, Helena, Schmidt, Reinhold, Schöttker, Ben, Schulz, Christina-Alexandra, Schupf, Nicole, Shaffer, Christian M., Shi, Yuan, Smith, Albert V., Smith, Blair H., Soranzo, Nicole, Spracklen, Cassandra N., Strauch, Konstantin, Stringham, Heather M., Stumvoll, Michael, Svensson, Per O., Szymczak, Silke, Tai, E-Shyong, Tajuddin, Salman M., Tan, Nicholas Y. Q., Taylor, Kent D., Teren, Andrej, Tham, Yih-Chung, Thiery, Joachim, Thio, Chris H. L., Thomsen, Hauke, Thorleifsson, Gudmar, Toniolo, Daniela, Tönjes, Anke, Tremblay, Johanne, Tzoulaki, Ioanna, Uitterlinden, André G., Vaccargiu, Simona, van Dam, Rob M., van der Harst, Pim, van Duijn, Cornelia M., Velez Edward, Digna R., Verweij, Niek, Vogelezang, suzanne, Völker, üwe, Vollenweider, Peter, Waeber, Gerard, Waldenberger, Melanie, Wallentin, Lars, Wang, Ya Xing, Wang, Chaolong, Waterworth, Dawn M., Bin Wei, Wen, White, Harvey, Whitfield, John B., Wild, Sarah H., Wilson, James F., Wojczynski, Mary K., Wong, Charlene, Wong, Tien-Yin, Xu, Liang, Yang, Qiong, Yasuda, Masayuki, Yerges-Armstrong, Laura M., Zhang, Weihua, Zonderman, Alan B., Rotter, Jerome I., Bochud, Murielle, Psaty, Bruce M., Vitart, Veronique, Wilson, James G., Dehghan, Abbas, Parsa, Afshin, Chasman, Daniel I., Ho, Kevin, Morris, Andrew P., Devuyst, Olivier, Akilesh, Shreeram, Pendergrass, Sarah A., Sim, Xueling, Böger, Carsten A., Okada, Yukinori, Edwards, Todd L., Snieder, Harold, Stefansson, Kari, Hung, Adriana M., Heid, Iris M., Markus Scholz, Teumer, Alexander, Köttgen, Anna, Pattaro, Cristian, Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Cardiovascular Centre (CVC), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Internal Medicine, Epidemiology, Erasmus MC other, Pediatrics, Psychiatry, APH - Mental Health, APH - Digital Health, Wuttke, M, Li, Y, Li, M, Sieber, Kb, Feitosa, Mf, Gorski, M, Tin, A, Wang, L, Chu, Ay, Hoppmann, A, Kirsten, H, Giri, A, Chai, Jf, Sveinbjornsson, G, Tayo, Bo, Nutile, T, Fuchsberger, C, Marten, J, Cocca, M, Ghasemi, S, Xu, Y, Horn, K, Noce, D, van der Most, Pj, Sedaghat, S, Yu, Z, Akiyama, M, Afaq, S, Ahluwalia, T, Almgren, P, Amin, N, Ärnlöv, J, Bakker, Sjl, Bansal, N, Baptista, D, Bergmann, S, Biggs, Ml, Biino, G, Boehnke, M, Boerwinkle, E, Boissel, M, Bottinger, Ep, Boutin, T, Brenner, H, Brumat, M, Burkhardt, R, Butterworth, A, Campana, Eric, Campbell, A, Campbell, H, Canouil, M, Carroll, Rj, Catamo, E, Chambers, Jc, Chee, Ml, Chen, X, Cheng, Cy, Cheng, Y, Christensen, K, Cifkova, R, Ciullo, M, Concas, Mp, Cook, Jp, Coresh, J, Corre, T, Sala, Cf, Cusi, D, Danesh, J, Daw, Ew, de Borst, Mh, De Grandi, A, de Mutsert, R, de Vries, Apj, Degenhardt, F, Delgado, G, Demirkan, A, Di Angelantonio, E, Dittrich, K, Divers, J, Dorajoo, R, Eckardt, Ku, Ehret, G, Elliott, P, Endlich, K, Evans, Mk, Felix, Jf, Foo, Vhx, Franco, Oh, Franke, A, Freedman, Bi, Freitag-Wolf, S, Friedlander, Y, Froguel, P, Gansevoort, Rt, Gao, H, Gasparini, P, Gaziano, Jm, Giedraitis, V, Gieger, C, Girotto, G, Giulianini, F, Gögele, M, Gordon, Sd, Gudbjartsson, Df, Gudnason, V, Haller, T, Hamet, P, Harris, Tb, Hartman, Ca, Hayward, C, Hellwege, Jn, Heng, Ck, Hicks, Aa, Hofer, E, Huang, W, Hutri-Kähönen, N, Hwang, Sj, Ikram, Ma, Indridason, O, Ingelsson, E, Ising, M, Jaddoe, Vwv, Jakobsdottir, J, Jonas, Jb, Joshi, Pk, Josyula, N, Jung, B, Kähönen, M, Kamatani, Y, Kammerer, Cm, Kanai, M, Kastarinen, M, Kerr, Sm, Khor, Cc, Kiess, W, Kleber, Me, Koenig, W, Kooner, J, Körner, A, Kovacs, P, Kraja, At, Krajcoviechova, A, Kramer, H, Krämer, Bk, Kronenberg, F, Kubo, M, Kühnel, B, Kuokkanen, M, Kuusisto, J, La Bianca, M, Laakso, M, Lange, La, Langefeld, Cd, Lee, Jj, Lehne, B, Lehtimäki, T, Lieb, W, Lifelines Cohort, Study, Lim, Sc, Lind, L, Lindgren, Cm, Liu, J, Loeffler, M, Loos, Rjf, Lucae, S, Lukas, Ma, Lyytikäinen, Lp, Mägi, R, Magnusson, Pke, Mahajan, A, Martin, Ng, Martins, J, März, W, Mascalzoni, D, Matsuda, K, Meisinger, C, Meitinger, T, Melander, O, Metspalu, A, Mikaelsdottir, Ek, Milaneschi, Y, Miliku, K, Mishra, Pp, V. A., Million Veteran Program, Mohlke, Kl, Mononen, N, Montgomery, Gw, Mook-Kanamori, Do, Mychaleckyj, Jc, Nadkarni, Gn, Nalls, Ma, Nauck, M, Nikus, K, Ning, B, Nolte, Im, Noordam, R, O'Connell, J, O'Donoghue, Ml, Olafsson, I, Oldehinkel, Aj, Orho-Melander, M, Ouwehand, Wh, Padmanabhan, S, Palmer, Nd, Palsson, R, Penninx, Bwjh, Perls, T, Perola, M, Pirastu, M, Pirastu, N, Pistis, G, Podgornaia, Ai, Polasek, O, Ponte, B, Porteous, Dj, Poulain, T, Pramstaller, Pp, Preuss, Mh, Prins, Bp, Province, Ma, Rabelink, Tj, Raffield, Lm, Raitakari, Ot, Reilly, Df, Rettig, R, Rheinberger, M, Rice, Km, Ridker, Pm, Rivadeneira, F, Rizzi, F, Roberts, Dj, Robino, A, Rossing, P, Rudan, I, Rueedi, R, Ruggiero, D, Ryan, Ka, Saba, Y, Sabanayagam, C, Salomaa, V, Salvi, E, Saum, Ku, Schmidt, H, Schmidt, R, Schöttker, B, Schulz, Ca, Schupf, N, Shaffer, Cm, Shi, Y, Smith, Av, Smith, Bh, Soranzo, N, Spracklen, Cn, Strauch, K, Stringham, Hm, Stumvoll, M, Svensson, Po, Szymczak, S, Tai, E, Tajuddin, Sm, Tan, Nyq, Taylor, Kd, Teren, A, Tham, Yc, Thiery, J, Thio, Chl, Thomsen, H, Thorleifsson, G, Toniolo, D, Tönjes, A, Tremblay, J, Tzoulaki, I, Uitterlinden, Ag, Vaccargiu, S, van Dam, Rm, van der Harst, P, van Duijn, Cm, Velez Edward, Dr, Verweij, N, Vogelezang, S, Völker, U, Vollenweider, P, Waeber, G, Waldenberger, M, Wallentin, L, Wang, Yx, Wang, C, Waterworth, Dm, Bin Wei, W, White, H, Whitfield, Jb, Wild, Sh, Wilson, Jf, Wojczynski, Mk, Wong, C, Wong, Ty, Xu, L, Yang, Q, Yasuda, M, Yerges-Armstrong, Lm, Zhang, W, Zonderman, Ab, Rotter, Ji, Bochud, M, Psaty, Bm, Vitart, V, Wilson, Jg, Dehghan, A, Parsa, A, Chasman, Di, Ho, K, Morris, Ap, Devuyst, O, Akilesh, S, Pendergrass, Sa, Sim, X, Böger, Ca, Okada, Y, Edwards, Tl, Snieder, H, Stefansson, K, Hung, Am, Heid, Im, Scholz, M, Teumer, A, Köttgen, A, and Pattaro, C.
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catalog ,Inheritance Patterns ,Hasso-Plattner-Institut für Digital Engineering GmbH ,Genome-wide association study ,Disease ,Kidney Function Tests ,Bioinformatics ,DISEASE ,0302 clinical medicine ,Uromodulin/urine ,kidney function ,11 Medical and Health Sciences ,Genetics & Heredity ,ddc:616 ,0303 health sciences ,Kidney ,Genome-wide association ,HERITABILITY ,GENOME-WIDE ASSOCIATION ,COMMON VARIANTS ,RENAL-FUNCTION ,TRANS-EQTLS ,METAANALYSIS ,TRANSPORTER ,CLASSIFICATION ,INTEGRATION ,Chromosome Mapping ,3. Good health ,Phenotype ,medicine.anatomical_structure ,Medical genetics ,Common variants ,Renal function ,Trans-EQTLS ,Metaanalysis ,Heritability ,Transporter ,Life Sciences & Biomedicine ,Glomerular Filtration Rate ,Metaanalysi ,medicine.medical_specialty ,Genotype ,European Continental Ancestry Group ,Quantitative Trait Loci ,Common variant ,Quantitative trait locus ,Biology ,Polymorphism, Single Nucleotide ,Article ,White People ,V. A. Million Veteran Program ,03 medical and health sciences ,Quantitative Trait, Heritable ,Lifelines Cohort Study ,Uromodulin ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Renal Insufficiency, Chronic ,Genetic Association Studies ,030304 developmental biology ,Genetic association ,Science & Technology ,urogenital system ,association ,genetic loci ,06 Biological Sciences ,medicine.disease ,Renal Insufficiency, Chronic/genetics/physiopathology/urine ,Genetic Association Studies/methods ,ddc:000 ,030217 neurology & neurosurgery ,Developmental Biology ,Genome-Wide Association Study ,Kidney disease - Abstract
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
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- 2019
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50. Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization
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Yuki Bradford, Toshiko Tanaka, Jeffrey R. O'Connell, Florence Kyndt, Unnur Thorsteinsdottir, Ivana Kolcic, Xiaoyan Yin, Vincent Probst, Manolis Kellis, Christopher Newton-Cheh, Stefan Kääb, Argelia Medeiros-Domingo, Markus M. Nöthen, Paolo Gasparini, Jean-Jacques Schott, Ruth J. F. Loos, Thomas W. Mühleisen, Annukka Marjamaa, Morris Brown, Igor Rudan, Runjun D. Kumar, Peter J. Schwartz, Lars Lind, Martina Müller-Nurasyid, Xinchen Wang, Joshua C. Denny, Roberto Insolia, Soumya Raychaudhuri, Stephen W. Scherer, Bruno H. Stricker, Alexander Kluttig, Adamo Pio D'Adamo, Laurie A. Boyer, Moritz F. Sinner, Norbert Frey, Nour Eddine El Mokhtari, Thomas Meitinger, Jesper V. Olsen, Gerjan Navis, Steven R. Cummings, Richard W Morris, Nynke Hofman, Marcel den Hoed, Rudolf A. de Boer, Gonçalo R. Abecasis, Mark J. Daly, Dan M. Roden, Christian Gieger, Lyudmyla Kedenko, Marcus Dörr, Thomas P. Cappola, Afshin Parsa, Kari Stefansson, Markus Perola, Mark Eijgelsheim, Fredrik Nyberg, Robert M. Hamilton, Yalda Jamshidi, W. H. Linda Kao, Terho Lehtimäki, Annette Peters, David Schlessinger, Peter P. Pramstaller, James F. Wilson, Vilmundur Gudnason, Florian Kronenberg, Aroon D. Hingorani, Connie R. Bezzina, Abdennasser Bardai, Marylyn D. Ritchie, Andrew S. Plump, Johan Sundström, Daryl Waggott, Chrysoula Dalageorgou, Paul I.W. de Bakker, Uwe Völker, Aaron Isaacs, Oscar H. Franco, Yongmei Liu, Andrew N. Nicolaides, Lia Crotti, Cornelia M. van Duijn, Ben A. Oostra, Arne Pfeufer, Karl Werdan, Michael Morley, Jan A. Kors, Julien Barc, Lewin Eisele, Siegfried Perz, Stéphanie Chatel, Pieter A. van der Vleuten, Sara L. Pulit, Anna F. Dominiczak, Harry Campbell, Alice Ghidoni, Irene Mateo Leach, Nona Sotoodehnia, Nina Mononen, Henriette E. Meyer zu Schwabedissen, Alvaro Alonso, Fabiola Del Greco M, Dan E. Arking, Vera Adamkova, Mike A. Nalls, Valur Emilsson, Edward G. Lakatta, Kirill Tarasov, Alan F. Wright, Lenore J. Launer, Erik Ingelsson, Karin Halina Greiser, Ozren Polasek, Massimo Carella, Daniel F. Gudbjartsson, Bouwe P. Krijthe, Hanna Prucha, Per Hoffmann, Maura Griffin, Stefan Kiechl, Angel Carracedo, Ilja M. Nolte, Christine E. Moravec, Johann Willeit, Joshua C. Bis, Patricia B. Munroe, Marcello Ricardo Paulista Markus, Hailiang Huang, Mika Kähönen, Albert Hofman, Peter H. Whincup, Dirk J. van Veldhuisen, Michael Knoflach, Alicia Lundby, Serena Sanna, Hagen Kälsch, Bernhard Paulweber, Kamil Slowikowski, Luigi Ferrucci, Melanie Waldenberger, Marco Bobbo, Annukka M. Lahtinen, Ann-Christine Syvänen, J. Gustav Smith, Åsa Torinsson Naluai, Jaroslav A. Hubacek, Jeffrey Brandimarto, Wendy S. Post, Lude Franke, Mark J. Caulfield, Folkert W. Asselbergs, André G. Uitterlinden, Stefan Gustafsson, Pim van der Harst, David J. Tester, David S. Siscovick, David O. Arnar, Sarah H Wild, Elizabeth J. Rossin, Albert V. Smith, Bruce M. Psaty, Georg Ehret, Alan R. Shuldiner, Stephen Newhouse, Kimmo Kontula, Maria Brion, Andre Franke, Peter W. Macfarlane, Mika Kivimäki, Tamara B. Harris, Lasse Oikarinen, Tamara T. Koopmann, Kenneth B. Margulies, Aravinda Chakravarti, Gianfranco Sinagra, Maarten P. van den Berg, Veikko Salomaa, Karl-Heinz Jöckel, Daniel S. Evans, Caroline Hayward, Kimmo Porthan, Michael J. Ackerman, Jacqueline C.M. Witteman, Arthur A.M. Wilde, Martin G. Larson, Kasper Lage, Manuela Uda, Susan R. Heckbert, Joel S. Bader, Graham Watt, María Dolores Torres, Stephan B. Felix, Jerome I. Rotter, Pau Navarro, Meena Kumari, Johan Ärnlöv, Andrew D. Paterson, Antti Jula, Olli T. Raitakari, Raimund Erbel, Christopher J. O'Donnell, Britt M. Beckmann, Peter A. Noseworthy, Tim D. Spector, Wai K. Lee, Leopoldo Zelante, Nilesh J. Samani, John R. Giudicessi, Harold Snieder, Dag S. Thelle, David Ellinghaus, Eimo Martens, James B. Strait, Jorma S. A. Viikari, Andrew D. Johnson, Antonella Mulas, Hilma Holm, Johannes Haerting, Annamaria Iorio, Rebecca L. Zuvich, Sheila Ulivi, Andrew A. Hicks, Elijah R. Behr, Leo-Pekka Lyytikäinen, Bernhard Strohmer, Marco Orru, Claudia Lamina, Sandosh Padmanabhan, Christian Fuchsberger, Andrie G. Panayiotou, Ehret, Georg Benedikt, Internal Medicine, Public Health, Epidemiology, Rehabilitation Medicine, Medical Informatics, Clinical Genetics, Cardiovascular Centre (CVC), Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Vascular Ageing Programme (VAP), Ethical, Legal, Social Issues in Genetics (ELSI), Stem Cell Aging Leukemia and Lymphoma (SALL), Arking, D, Pulit, S, Crotti, L, van der Harst, P, Munroe, P, Koopmann, T, Sotoodehnia, N, Rossin, E, Morley, M, Wang, X, Johnson, A, Lundby, A, Gudbjartsson, D, Noseworthy, P, Eijgelsheim, M, Bradford, Y, Tarasov, K, Dörr, M, Müller-Nurasyid, M, Lahtinen, A, Nolte, I, Smith, A, Bis, J, Isaacs, A, Newhouse, S, Evans, D, Post, W, Waggott, D, Lyytikäinen, L, Hicks, A, Eisele, L, Ellinghaus, D, Hayward, C, Navarro, P, Ulivi, S, Tanaka, T, Tester, D, Chatel, S, Gustafsson, S, Kumari, M, Morris, R, Naluai, A, Padmanabhan, S, Kluttig, A, Strohmer, B, Panayiotou, A, Torres, M, Knoflach, M, Hubacek, J, Slowikowski, K, Raychaudhuri, S, Kumar, R, Harris, T, Launer, L, Shuldiner, A, Alonso, A, Bader, J, Ehret, G, Huang, H, Kao, W, Strait, J, Macfarlane, P, Brown, M, Caulfield, M, Samani, N, Kronenberg, F, Willeit, J, Smith, J, Greiser, K, Meyer Zu Schwabedissen, H, Werdan, K, Carella, M, Zelante, L, Heckbert, S, Psaty, B, Rotter, J, Kolcic, I, Polašek, O, Wright, A, Griffin, M, Daly, M, Arnar, D, Hólm, H, Thorsteinsdottir, U, Denny, J, Roden, D, Zuvich, R, Emilsson, V, Plump, A, Larson, M, O'Donnell, C, Yin, X, Bobbo, M, D'Adamo, A, Iorio, A, Sinagra, G, Carracedo, A, Cummings, S, Nalls, M, Jula, A, Kontula, K, Marjamaa, A, Oikarinen, L, Perola, M, Porthan, K, Erbel, R, Hoffmann, P, Jöckel, K, Kälsch, H, Nöthen, M, den Hoed, M, Loos, R, Thelle, D, Gieger, C, Meitinger, T, Perz, S, Peters, A, Prucha, H, Sinner, M, Waldenberger, M, de Boer, R, Franke, L, van der Vleuten, P, Beckmann, B, Martens, E, Bardai, A, Hofman, N, Wilde, A, Behr, E, Dalageorgou, C, Giudicessi, J, Medeiros-Domingo, A, Kyndt, F, Probst, V, Ghidoni, A, Insolia, R, Hamilton, R, Scherer, S, Brandimarto, J, Margulies, K, Moravec, C, Greco, M, Fuchsberger, C, O'Connell, J, Lee, W, Watt, G, Campbell, H, Wild, S, El Mokhtari, N, Frey, N, Asselbergs, F, Mateo Leach, I, Navis, G, van den Berg, M, van Veldhuisen, D, Kellis, M, Krijthe, B, Franco, O, Hofman, A, Kors, J, Uitterlinden, A, Witteman, J, Kedenko, L, Lamina, C, Oostra, B, Abecasis, G, Lakatta, E, Mulas, A, Orrú, M, Schlessinger, D, Uda, M, Markus, M, Völker, U, Snieder, H, Spector, T, Arnlöv, J, Lind, L, Sundström, J, Syvänen, A, Kivimaki, M, Kähönen, M, Mononen, N, Raitakari, O, Viikari, J, Adamkova, V, Kiechl, S, Brion, M, Nicolaides, A, Paulweber, B, Haerting, J, Dominiczak, A, Nyberg, F, Whincup, P, Hingorani, A, Schott, J, Bezzina, C, Ingelsson, E, Ferrucci, L, Gasparini, P, Wilson, J, Rudan, I, Franke, A, Mühleisen, T, Pramstaller, P, Lehtimäki, T, Paterson, A, Parsa, A, Liu, Y, van Duijn, C, Siscovick, D, Gudnason, V, Jamshidi, Y, Salomaa, V, Felix, S, Sanna, S, Ritchie, M, Stricker, B, Stefansson, K, Boyer, L, Cappola, T, Olsen, J, Lage, K, Schwartz, P, Kääb, S, Chakravarti, A, Ackerman, M, Pfeufer, A, de Bakker, P, Newton-Cheh, C, Arking, Dan E., Pulit, Sara L., Crotti, Lia, Van Der Harst, Pim, Munroe, Patricia B., Koopmann, Tamara T., Sotoodehnia, Nona, Rossin, Elizabeth J., Morley, Michael, Wang, Xinchen, Johnson, Andrew D., Lundby, Alicia, Gudbjartsson, Daníel F., Noseworthy, Peter A., Eijgelsheim, Mark, Bradford, Yuki, Tarasov, Kirill V., Dörr, Marcu, Müller Nurasyid, Martina, Lahtinen, Annukka M., Nolte, Ilja M., Smith, Albert Vernon, Bis, Joshua C., Isaacs, Aaron, Newhouse, Stephen J., Evans, Daniel S., Post, Wendy S., Waggott, Daryl, Lyytikäinen, Leo Pekka, Hicks, Andrew A., Eisele, Lewin, Ellinghaus, David, Hayward, Caroline, Navarro, Pau, Ulivi, Sheila, Tanaka, Toshiko, Tester, David J., Chatel, Stéphanie, Gustafsson, Stefan, Kumari, Meena, Morris, Richard W., Naluai, Asa T., Padmanabhan, Sandosh, Kluttig, Alexander, Strohmer, Bernhard, Panayiotou, Andrie G., Torres, Maria, Knoflach, Michael, Hubacek, Jaroslav A., Slowikowski, Kamil, Raychaudhuri, Soumya, Kumar, Runjun D., Harris, Tamara B., Launer, Lenore J., Shuldiner, Alan R., Alonso, Alvaro, Bader, Joel S., Ehret, Georg, Huang, Hailiang, Kao, W. H. Linda, Strait, James B., Macfarlane, Peter W., Brown, Morri, Caulfield, Mark J., Samani, Nilesh J., Kronenberg, Florian, Willeit, Johann, Smith, J. Gustav, Greiser, Karin H., Zu Schwabedissen, Henriette Meyer, Werdan, Karl, Carella, Massimo, Zelante, Leopoldo, Heckbert, Susan R., Psaty, Bruce M., Rotter, Jerome I., Kolcic, Ivana, Polašek, Ozren, Wright, Alan F., Griffin, Maura, Daly, Mark J., Arnar, David O., Hólm, Hilma, Thorsteinsdottir, Unnur, Denny, Joshua C., Roden, Dan M., Zuvich, Rebecca L., Emilsson, Valur, Plump, Andrew S., Larson, Martin G., O'Donnell, Christopher J., Yin, Xiaoyan, Bobbo, Marco, D'Adamo, ADAMO PIO, Iorio, Annamaria, Sinagra, Gianfranco, Carracedo, Angel, Cummings, Steven R., Nalls, Michael A., Jula, Antti, Kontula, Kimmo K., Marjamaa, Annukka, Oikarinen, Lasse, Perola, Marku, Porthan, Kimmo, Erbel, Raimund, Hoffmann, Per, Jöckel, Karl Heinz, Kälsch, Hagen, Nöthen, Markus M., Den Hoed, Marcel, Loos, Ruth J. F., Thelle, Dag S., Gieger, Christian, Meitinger, Thoma, Perz, Siegfried, Peters, Annette, Prucha, Hanna, Sinner, Moritz F., Waldenberger, Melanie, De Boer, Rudolf A., Franke, Lude, Van Der Vleuten, Pieter A., Beckmann, Britt Maria, Martens, Eimo, Bardai, Abdennasser, Hofman, Nynke, Wilde, Arthur A. M., Behr, Elijah R., Dalageorgou, Chrysoula, Giudicessi, John R., Medeiros Domingo, Argelia, Barc, Julien, Kyndt, Florence, Probst, Vincent, Ghidoni, Alice, Insolia, Roberto, Hamilton, Robert M., Scherer, Stephen W., Brandimarto, Jeffrey, Margulies, Kenneth, Moravec, Christine E., Del Greco M, Fabiola, Fuchsberger, Christian, O'Connell, Jeffrey R., Lee, Wai K., Watt, Graham C. M., Campbell, Harry, Wild, Sarah H., El Mokhtari, Nour E., Frey, Norbert, Asselbergs, Folkert W., Leach, Irene Mateo, Navis, Gerjan, Van Den Berg, Maarten P., Van Veldhuisen, Dirk J., Kellis, Manoli, Krijthe, Bouwe P., Franco, Oscar H., Hofman, Albert, Kors, Jan A., Uitterlinden, André G., Witteman, Jacqueline C. M., Kedenko, Lyudmyla, Lamina, Claudia, Oostra, Ben A., Abecasis, Gonçalo R., Lakatta, Edward G., Mulas, Antonella, Orrú, Marco, Schlessinger, David, Uda, Manuela, Markus, Marcello R. P., Völker, Uwe, Snieder, Harold, Spector, Timothy D., Ärnlöv, Johan, Lind, Lar, Sundström, Johan, Syvänen, Ann Christine, Kivimaki, Mika, Kähönen, Mika, Mononen, Nina, Raitakari, Olli T., Viikari, Jorma S., Adamkova, Vera, Kiechl, Stefan, Brion, Maria, Nicolaides, Andrew N., Paulweber, Bernhard, Haerting, Johanne, Dominiczak, Anna F., Nyberg, Fredrik, Whincup, Peter H., Hingorani, Aroon D., Schott, Jean Jacque, Bezzina, Connie R., Ingelsson, Erik, Ferrucci, Luigi, Gasparini, Paolo, Wilson, James F., Rudan, Igor, Franke, Andre, Mühleisen, Thomas W., Pramstaller, Peter P., Lehtimäki, Terho J., Paterson, Andrew D., Parsa, Afshin, Liu, Yongmei, Van Duijn, Cornelia M., Siscovick, David S., Gudnason, Vilmundur, Jamshidi, Yalda, Salomaa, Veikko, Felix, Stephan B., Sanna, Serena, Ritchie, Marylyn D., Stricker, Bruno H., Stefansson, Kari, Boyer, Laurie A., Cappola, Thomas P., Olsen, Jesper V., Lage, Kasper, Schwartz, Peter J., Kääb, Stefan, Chakravarti, Aravinda, Ackerman, Michael J., Pfeufer, Arne, De Bakker, Paul I. W., Newton Cheh, Christopher, Cardiology, ACS - Amsterdam Cardiovascular Sciences, and Human Genetics
- Subjects
Male ,Candidate gene ,Myocardium/metabolism ,LOCI ,Medizin ,Heart electrophysiology ,Genome-wide association study ,Arrhythmias ,Bioinformatics ,Medical and Health Sciences ,Heart Ventricle ,Sudden cardiac death ,Electrocardiography ,PR INTERVAL ,Arrhythmias, Cardiac/genetics ,Death, Sudden, Cardiac/etiology ,Genetics ,ddc:616 ,Cardiac electrophysiology ,Adult ,Aged ,Arrhythmias, Cardiac ,Calcium Signaling ,Death, Sudden, Cardiac ,Female ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Genotype ,Heart Ventricles ,Humans ,Long QT Syndrome ,Middle Aged ,Myocardium ,Polymorphism, Single Nucleotide ,COMMON VARIANTS ,Heart Ventricles/metabolism ,Single Nucleotide ,Long QT Syndrome/genetics ,CHRONIC HEART-FAILURE ,Death ,Heart ventricle arrhythmia ,genetic association study ,gene ,SNP ,heart ,Genome-Wide Association Study/methods ,Long QT syndrome ,QRS DURATION ,Cardiac ,Cardiac/etiology ,Human ,QT interval ,congenital, hereditary, and neonatal diseases and abnormalities ,Electrocardiography/methods ,TRPM7 ,BIO/18 - GENETICA ,Cardiac/genetics ,Biology ,Article ,sudden cardiac death ,QRS complex ,CARDIAC REPOLARIZATION ,medicine ,Repolarization ,cardiovascular diseases ,GENOME-WIDE ASSOCIATION ,Polymorphism ,MED/01 - STATISTICA MEDICA ,calcium ,ta1184 ,Calcium signaling ,Calcium Signaling/genetics ,MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE ,ta3121 ,Cardiovascular risk ,medicine.disease ,SARCOPLASMIC-RETICULUM ,Sudden ,MODEL ,Genetic association ,myocardial repolarization ,Genetic variability ,Gene expression ,Clinical Medicine ,genetic ,Controlled study - 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 similar to 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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