4,641 results on '"Hamsten,A"'
Search Results
102. Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease
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van Meurs, Joyce BJ, Pare, Guillaume, Schwartz, Stephen M, Hazra, Aditi, Tanaka, Toshiko, Vermeulen, Sita H, Cotlarciuc, Ioana, Yuan, Xin, Mälarstig, Anders, Bandinelli, Stefania, Bis, Joshua C, Blom, Henk, Brown, Morris J, Chen, Constance, Chen, Yii-Der, Clarke, Robert J, Dehghan, Abbas, Erdmann, Jeanette, Ferrucci, Luigi, Hamsten, Anders, Hofman, Albert, Hunter, David J, Goel, Anuj, Johnson, Andrew D, Kathiresan, Sekar, Kampman, Ellen, Kiel, Douglas P, Kiemeney, Lambertus ALM, Chambers, John C, Kraft, Peter, Lindemans, Jan, McKnight, Barbara, Nelson, Christopher P, O’Donnell, Christopher J, Psaty, Bruce M, Ridker, Paul M, Rivadeneira, Fernando, Rose, Lynda M, Seedorf, Udo, Siscovick, David S, Schunkert, Heribert, Selhub, Jacob, Ueland, Per M, Vollenweider, Peter, Waeber, Gérard, Waterworth, Dawn M, Watkins, Hugh, Witteman, Jacqueline CM, den Heijer, Martin, Jacques, Paul, Uitterlinden, Andre G, Kooner, Jaspal S, Rader, Dan J, Reilly, Muredach P, Mooser, Vincent, Chasman, Daniel I, Samani, Nilesh J, and Ahmadi, Kourosh R
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- 2013
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103. Meta-analysis of Gene-Level Associations for Rare Variants Based on Single-Variant Statistics
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Berndt, Sonja I., Gustafsson, Stefan, Mägi, Reedik, Ganna, Andrea, Wheeler, Eleanor, Feitosa, Mary F., Justice, Anne E., Monda, Keri L., Croteau-Chonka, Damien C., Day, Felix R., Esko, Tõnu, Fall, Tove, Ferreira, Teresa, Gentilini, Davide, Jackson, Anne U., Luan, Jian’an, Randall, Joshua C., Vedantam, Sailaja, Willer, Cristen J., Winkler, Thomas W., Wood, Andrew R., Workalemahu, Tsegaselassie, Hu, Yi-Juan, Lee, Sang Hong, Liang, Liming, Lin, Dan-Yu, Min, Josine L., Neale, Benjamin M., Thorleifsson, Gudmar, Yang, Jian, Albrecht, Eva, Amin, Najaf, Bragg-Gresham, Jennifer L., Cadby, Gemma, den Heijer, Martin, Eklund, Niina, Fischer, Krista, Goel, Anuj, Hottenga, Jouke-Jan, Huffman, Jennifer E., Jarick, Ivonne, Johansson, Åsa, Johnson, Toby, Kanoni, Stavroula, Kleber, Marcus E., König, Inke R., Kristiansson, Kati, Kutalik, Zoltán, Lamina, Claudia, Lecoeur, Cecile, Li, Guo, Mangino, Massimo, McArdle, Wendy L., Medina-Gomez, Carolina, Müller-Nurasyid, Martina, Ngwa, Julius S., Nolte, Ilja M., Paternoster, Lavinia, Pechlivanis, Sonali, Perola, Markus, Peters, Marjolein J., Preuss, Michael, Rose, Lynda M., Shi, Jianxin, Shungin, Dmitry, Smith, Albert Vernon, Strawbridge, Rona J., Surakka, Ida, Teumer, Alexander, Trip, Mieke D., Tyrer, Jonathan, Van Vliet-Ostaptchouk, Jana V., Vandenput, Liesbeth, Waite, Lindsay L., Zhao, Jing Hua, Absher, Devin, Asselbergs, Folkert W., Atalay, Mustafa, Attwood, Antony P., Balmforth, Anthony J., Basart, Hanneke, Beilby, John, Bonnycastle, Lori L., Brambilla, Paolo, Bruinenberg, Marcel, Campbell, Harry, Chasman, Daniel I., Chines, Peter S., Collins, Francis S., Connell, John M., Cookson, William, de Faire, Ulf, de Vegt, Femmie, Dei, Mariano, Dimitriou, Maria, Edkins, Sarah, Estrada, Karol, Evans, David M., Farrall, Martin, Ferrario, Marco M., Ferrières, Jean, Franke, Lude, Frau, Francesca, Gejman, Pablo V., Grallert, Harald, Grönberg, Henrik, Gudnason, Vilmundur, Hall, Alistair S., Hall, Per, Hartikainen, Anna-Liisa, Hayward, Caroline, Heard-Costa, Nancy L., Heath, Andrew C., Hebebrand, Johannes, Homuth, Georg, Hu, Frank B., Hunt, Sarah E., Hyppönen, Elina, Iribarren, Carlos, Jacobs, Kevin B., Jansson, John-Olov, Jula, Antti, Kähönen, Mika, Kathiresan, Sekar, Kee, Frank, Khaw, Kay-Tee, Kivimaki, Mika, Koenig, Wolfgang, Kraja, Aldi T., Kumari, Meena, Kuulasmaa, Kari, Kuusisto, Johanna, Laitinen, Jaana H., Lakka, Timo A., Langenberg, Claudia, Launer, Lenore J., Lind, Lars, Lindström, Jaana, Liu, Jianjun, Liuzzi, Antonio, Lokki, Marja-Liisa, Lorentzon, Mattias, Madden, Pamela A., Magnusson, Patrik K., Manunta, Paolo, Marek, Diana, März, Winfried, Leach, Irene Mateo, McKnight, Barbara, Medland, Sarah E., Mihailov, Evelin, Milani, Lili, Montgomery, Grant W., Mooser, Vincent, Mühleisen, Thomas W., Munroe, Patricia B., Musk, Arthur W., Narisu, Narisu, Navis, Gerjan, Nicholson, George, Nohr, Ellen A., Ong, Ken K., Oostra, Ben A., Palmer, Colin N.A., Palotie, Aarno, Peden, John F., Pedersen, Nancy, Peters, Annette, Polasek, Ozren, Pouta, Anneli, Pramstaller, Peter P., Prokopenko, Inga, Pütter, Carolin, Radhakrishnan, Aparna, Raitakari, Olli, Rendon, Augusto, Rivadeneira, Fernando, Rudan, Igor, Saaristo, Timo E., Sambrook, Jennifer G., Sanders, Alan R., Sanna, Serena, Saramies, Jouko, Schipf, Sabine, Schreiber, Stefan, Schunkert, Heribert, Shin, So-Youn, Signorini, Stefano, Sinisalo, Juha, Skrobek, Boris, Soranzo, Nicole, Stančáková, Alena, Stark, Klaus, Stephens, Jonathan C., Stirrups, Kathleen, Stolk, Ronald P., Stumvoll, Michael, Swift, Amy J., Theodoraki, Eirini V., Thorand, Barbara, Tregouet, David-Alexandre, Tremoli, Elena, Van der Klauw, Melanie M., van Meurs, Joyce B.J., Vermeulen, Sita H., Viikari, Jorma, Virtamo, Jarmo, Vitart, Veronique, Waeber, Gérard, Wang, Zhaoming, Widén, Elisabeth, Wild, Sarah H., Willemsen, Gonneke, Winkelmann, Bernhard R., Witteman, Jacqueline C.M., Wolffenbuttel, Bruce H.R., Wong, Andrew, Wright, Alan F., Zillikens, M. Carola, Amouyel, Philippe, Boehm, Bernhard O., Boerwinkle, Eric, Boomsma, Dorret I., Caulfield, Mark J., Chanock, Stephen J., Cupples, L. Adrienne, Cusi, Daniele, Dedoussis, George V., Erdmann, Jeanette, Eriksson, Johan G., Franks, Paul W., Froguel, Philippe, Gieger, Christian, Gyllensten, Ulf, Hamsten, Anders, Harris, Tamara B., Hengstenberg, Christian, Hicks, Andrew A., Hingorani, Aroon, Hinney, Anke, Hofman, Albert, Hovingh, Kees G., Hveem, Kristian, Illig, Thomas, Jarvelin, Marjo-Riitta, Jöckel, Karl-Heinz, Keinanen-Kiukaanniemi, Sirkka M., Kiemeney, Lambertus A., Kuh, Diana, Laakso, Markku, Lehtimäki, Terho, Levinson, Douglas F., Martin, Nicholas G., Metspalu, Andres, Morris, Andrew D., Nieminen, Markku S., Njølstad, Inger, Ohlsson, Claes, Oldehinkel, Albertine J., Ouwehand, Willem H., Palmer, Lyle J., Penninx, Brenda, Power, Chris, Province, Michael A., Psaty, Bruce M., Qi, Lu, Rauramaa, Rainer, Ridker, Paul M., Ripatti, Samuli, Salomaa, Veikko, Samani, Nilesh J., Snieder, Harold, Sørensen, Thorkild I.A., Spector, Timothy D., Stefansson, Kari, Tönjes, Anke, Tuomilehto, Jaakko, Uitterlinden, André G., Uusitupa, Matti, van der Harst, Pim, Vollenweider, Peter, Wallaschofski, Henri, Wareham, Nicholas J., Watkins, Hugh, Wichmann, H.-Erich, Wilson, James F., Abecasis, Goncalo R., Assimes, Themistocles L., Barroso, Inês, Boehnke, Michael, Borecki, Ingrid B., Deloukas, Panos, Fox, Caroline S., Frayling, Timothy, Groop, Leif C., Haritunian, Talin, Heid, Iris M., Hunter, David, Kaplan, Robert C., Karpe, Fredrik, Moffatt, Miriam, Mohlke, Karen L., O’Connell, Jeffrey R., Pawitan, Yudi, Schadt, Eric E., Schlessinger, David, Steinthorsdottir, Valgerdur, Strachan, David P., Thorsteinsdottir, Unnur, van Duijn, Cornelia M., Visscher, Peter M., Di Blasio, Anna Maria, Hirschhorn, Joel N., Lindgren, Cecilia M., Morris, Andrew P., Meyre, David, Scherag, André, McCarthy, Mark I., Speliotes, Elizabeth K., North, Kari E., Loos, Ruth J.F., Ingelsson, Erik, and Hirschhorn, Joel
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- 2013
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104. Network-Based Multiple Sclerosis Pathway Analysis with GWAS Data from 15,000 Cases and 30,000 Controls
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Baranzini, Sergio E., Khankhanian, Pouya, Patsopoulos, Nikolaos A., Li, Michael, Stankovich, Jim, Cotsapas, Chris, Søndergaard, Helle Bach, Ban, Maria, Barizzone, Nadia, Bergamaschi, Laura, Booth, David, Buck, Dorothea, Cavalla, Paola, Celius, Elisabeth G., Comabella, Manuel, Comi, Giancarlo, Compston, Alastair, Cournu-Rebeix, Isabelle, D’alfonso, Sandra, Damotte, Vincent, Din, Lennox, Dubois, Bénédicte, Elovaara, Irina, Esposito, Federica, Fontaine, Bertrand, Franke, Andre, Goris, An, Gourraud, Pierre-Antoine, Graetz, Christiane, Guerini, Franca R., Guillot-Noel, Léna, Hafler, David, Hakonarson, Hakon, Hall, Per, Hamsten, Anders, Harbo, Hanne F., Hemmer, Bernhard, Hillert, Jan, Kemppinen, Anu, Kockum, Ingrid, Koivisto, Keijo, Larsson, Malin, Lathrop, Mark, Leone, Maurizio, Lill, Christina M., Macciardi, Fabio, Martin, Roland, Martinelli, Vittorio, Martinelli-Boneschi, Filippo, McCauley, Jacob L., Myhr, Kjell-Morten, Naldi, Paola, Olsson, Tomas, Oturai, Annette, Pericak-Vance, Margaret A., Perla, Franco, Reunanen, Mauri, Saarela, Janna, Saker-Delye, Safa, Salvetti, Marco, Sellebjerg, Finn, Sørensen, Per Soelberg, Spurkland, Anne, Stewart, Graeme, Taylor, Bruce, Tienari, Pentti, Winkelmann, Juliane, Zipp, Frauke, Ivinson, Adrian J., Haines, Jonathan L., Sawcer, Stephen, DeJager, Philip, Hauser, Stephen L., and Oksenberg, Jorge R.
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- 2013
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105. Genetic determinants of plasma β2-glycoprotein I levels: a genome-wide association study in extended pedigrees from Spain
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Athanasiadis, G., Sabater-Lleal, M., Buil, A., Souto, J.C., Borrell, M., Lathrop, M., Watkins, H., Almasy, L., Hamsten, A., and Soria, J.M.
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- 2013
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106. A gene-centric study of common carotid artery remodelling
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Harrison, Seamus C., Zabaneh, Delilah, Asselbergs, Folkert W., Drenos, Fotios, Jones, Gregory T., Shah, Sonia, Gertow, Karl, Sennblad, Bengt, Strawbridge, Rona J., Gigante, Bruna, Holewijn, Suzanne, De Graaf, Jacqueline, Vermeulen, Sita, Folkersen, Lasse, van Rij, Andre M., Baldassarre, Damiano, Veglia, Fabrizio, Talmud, Philippa J., Deanfield, John E., Agu, Obi, Kivimaki, Mika, Kumari, Meena, Bown, Matthew J., Nyyssönen, Kristiina, Rauramaa, Rainer, Smit, Andries J., Franco-Cereceda, Anders, Giral, Philippe, Mannarino, Elmo, Silveira, Angela, Syvänen, Ann-Christine, de Borst, Gert J., van der Graaf, Yolanda, de Faire, Ulf, Baas, Annette F., Blankensteijn, Jan D., Wareham, Nicholas J., Fowkes, Gerry, Tzoulaki, Ionna, Price, Jacqueline F., Tremoli, Elena, Hingorani, Aroon D., Eriksson, Per, Hamsten, Anders, and Humphries, Steve E.
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- 2013
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107. Plasma Protein Profile of Carotid Artery Atherosclerosis and Atherosclerotic Outcomes
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Elena Tremoli, Pär Hedberg, Tobias Feldreich, Bruna Gigante, Marju Orho-Melander, Jerzy Leppert, Lars Lind, Anders Hamsten, Johan Sundström, Carl Johan Östgren, Anders Mälarstig, Fabrizio Veglia, Christopher J. O'Donnell, Nora Franceschini, Fredrik H. Nystrom, Gunnar Engström, Johan Ärnlöv, Olle Melander, Yan Borné, Jan Nilsson, and Damiano Baldassarre
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Carotid Artery Diseases ,Male ,Proteomics ,medicine.medical_specialty ,Proteome ,medicine.drug_class ,Carotid Intima-Media Thickness ,Risk Assessment ,Risk Factors ,Matrix Metalloproteinase 12 ,medicine.artery ,Internal medicine ,Mendelian randomization ,medicine ,Natriuretic peptide ,Humans ,Cardiac and Cardiovascular Systems ,cardiovascular diseases ,Common carotid artery ,Myocardial infarction ,Receptor ,Aged ,Sweden ,Kardiologi ,business.industry ,Incidence ,Genetic Variation ,Mendelian Randomization Analysis ,Blood Proteins ,Middle Aged ,Prognosis ,medicine.disease ,Blood proteins ,Plaque, Atherosclerotic ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business ,Biomarkers ,Lipoprotein - Abstract
Objective: To identify causal pathophysiological mechanisms for atherosclerosis and incident cardiovascular events using protein measurements. Approach and Results: Carotid artery atherosclerosis was assessed by ultrasound, and 86 cardiovascular-related proteins were measured using the Olink CVD-I panel in 7 Swedish prospective studies (11 754 individuals). The proteins were analyzed in relation to intima-media thickness in the common carotid artery (IMT-CCA), plaque occurrence, and incident cardiovascular events (composite end point of myocardial infarction or ischemic stroke) using a discovery/replication approach in different studies. After adjustments for traditional cardiovascular risk factors, 11 proteins remained significantly associated with IMT-CCA in the replication stage, whereas 9 proteins were replicated for plaque occurrence and 17 proteins for incident cardiovascular events. NT-proBNP (N-terminal pro-B-type natriuretic peptide) and MMP (matrix metalloproteinase)-12 were associated with both IMT-CCA and incident events, but the overlap was considerably larger between plaque occurrence and incident events, including MMP-12, TIM-1 (T-cell immunoglobulin and mucin domain 1), GDF (growth/differentiation factor)-15, IL (interleukin)-6, U-PAR (urokinase plasminogen activator surface receptor), LOX-1 (lectin-like oxidized LDL [low-density lipoprotein] receptor 1), and TRAIL-R2 (TNF [tumor necrosis factor]-related apoptosis-inducing ligand receptor 2). Only MMP-12 was associated with IMT-CCA, plaque, and incident events with a positive and concordant direction of effect. However, a 2-sample Mendelian randomization analysis suggested that increased MMP-12 may be protective against ischemic stroke ( P =5.5×10 −7 ), which is in the opposite direction of the observational analyses. Conclusions: The present meta-analysis discovered several proteins related to carotid atherosclerosis that partly differed in their association with IMT-CCA, plaque, and incident atherosclerotic disease. Mendelian randomization analysis for the top finding, MMP-12, suggests that the increased levels of MMP-12 could be a consequence of atherosclerotic burden rather than the opposite chain of events.
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- 2021
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108. Diabetes: A Growing CHD Epidemic
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Diabetes Atherosclerosis Intervention Study Investigators, Hamsten, Anders, Steiner, George, Fruchart, J.-C., editor, Gotto, A. M., Jr., editor, Paoletti, R., editor, Staels, B., editor, and Catapano, A. L., editor
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- 2002
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109. Fatty acid binding protein expression in different human adipose tissue depots in relation to rates of lipolysis and insulin concentration in obese individuals
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Fisher, R. M., Thörne, A., Hamsten, A., Arner, P., and Glatz, Jan F. C., editor
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- 2002
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110. Abstract 20011: Novel Genetic Variants Associated With Circulating Soluble Glycoprotein 130 Levels in The IMPROVE Study
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Bonomi, Alice, Veglia, Fabrizio, Baldassarre, Damiano, Golabkesh, Zahra, Strawbridge, Rona, Hamsten, Anders, Tremoli, Elena, de Faire, Ulf, and Gigante, Bruna
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- 2017
111. Integrative studies implicate matrix metalloproteinase‐12 as a culprit gene for large‐artery atherosclerotic stroke
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Mahdessian, H., Perisic Matic, L., Lengquist, M., Gertow, K., Sennblad, B., Baldassarre, D., Veglia, F., Humphries, S. E., Rauramaa, R., de Faire, U., Smit, A. J., Giral, P., Kurl, S., Mannarino, E., Tremoli, E., Hamsten, A., Eriksson, P., Hedin, U., and Mälarstig, A.
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- 2017
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112. Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney
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Wain, Louise V., Vaez, Ahmad, Jansen, Rick, Joehanes, Roby, van der Most, Peter J., Erzurumluoglu, A. Mesut, O’Reilly, Paul F., Cabrera, Claudia P., Warren, Helen R., Rose, Lynda M., Verwoert, Germaine C., Hottenga, Jouke-Jan, Strawbridge, Rona J., Esko, Tonu, Arking, Dan E., Hwang, Shih-Jen, Guo, Xiuqing, Kutalik, Zoltan, Trompet, Stella, Shrine, Nick, Teumer, Alexander, Ried, Janina S., Bis, Joshua C., Smith, Albert V., Amin, Najaf, Nolte, Ilja M., Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Wareham, Nicholas J., Hofer, Edith, Joshi, Peter K., Kristiansson, Kati, Traglia, Michela, Havulinna, Aki S., Goel, Anuj, Nalls, Mike A., Sõber, Siim, Vuckovic, Dragana, Luan, Jian’an, Del Greco M., Fabiola, Ayers, Kristin L., Marrugat, Jaume, Ruggiero, Daniela, Lopez, Lorna M., Niiranen, Teemu, Enroth, Stefan, Jackson, Anne U., Nelson, Christopher P., Huffman, Jennifer E., Zhang, Weihua, Marten, Jonathan, Gandin, Ilaria, Harris, Sarah E., Zemunik, Tatijana, Lu, Yingchang, Evangelou, Evangelos, Shah, Nabi, de Borst, Martin H., Mangino, Massimo, Prins, Bram P., Campbell, Archie, Li-Gao, Ruifang, Chauhan, Ganesh, Oldmeadow, Christopher, Abecasis, Gonçalo, Abedi, Maryam, Barbieri, Caterina M., Barnes, Michael R., Batini, Chiara, Beilby, John, Blake, Tineka, Boehnke, Michael, Bottinger, Erwin P., Braund, Peter S., Brown, Morris, Brumat, Marco, Campbell, Harry, Chambers, John C., Cocca, Massimiliano, Collins, Francis, Connell, John, Cordell, Heather J., Damman, Jeffrey J., Davies, Gail, de Geus, Eco J., de Mutsert, Renée, Deelen, Joris, Demirkale, Yusuf, Doney, Alex S.F., Dörr, Marcus, Farrall, Martin, Ferreira, Teresa, Frånberg, Mattias, Gao, He, Giedraitis, Vilmantas, Gieger, Christian, Giulianini, Franco, Gow, Alan J., Hamsten, Anders, Harris, Tamara B., Hofman, Albert, Holliday, Elizabeth G., Hui, Jennie, Jarvelin, Marjo-Riitta, Johansson, Åsa, Johnson, Andrew D., Jousilahti, Pekka, Jula, Antti, Kähönen, Mika, Kathiresan, Sekar, Khaw, Kay-Tee, Kolcic, Ivana, Koskinen, Seppo, Langenberg, Claudia, Larson, Marty, Launer, Lenore J., Lehne, Benjamin, Liewald, David C.M., Lin, Li, Lind, Lars, Mach, François, Mamasoula, Chrysovalanto, Menni, Cristina, Mifsud, Borbala, Milaneschi, Yuri, Morgan, Anna, Morris, Andrew D., Morrison, Alanna C., Munson, Peter J., Nandakumar, Priyanka, Nguyen, Quang Tri, Nutile, Teresa, Oldehinkel, Albertine J., Oostra, Ben A., Org, Elin, Padmanabhan, Sandosh, Palotie, Aarno, Paré, Guillaume, Pattie, Alison, Penninx, Brenda W.J.H., Poulter, Neil, Pramstaller, Peter P., Raitakari, Olli T., Ren, Meixia, Rice, Kenneth, Ridker, Paul M., Riese, Harriëtte, Ripatti, Samuli, Robino, Antonietta, Rotter, Jerome I., Rudan, Igor, Saba, Yasaman, Saint Pierre, Aude, Sala, Cinzia F., Sarin, Antti-Pekka, Schmidt, Reinhold, Scott, Rodney, Seelen, Marc A., Shields, Denis C., Siscovick, David, Sorice, Rossella, Stanton, Alice, Stott, David J., Sundström, Johan, Swertz, Morris, Taylor, Kent D., Thom, Simon, Tzoulaki, Ioanna, Tzourio, Christophe, Uitterlinden, André G., Völker, Uwe, Vollenweider, Peter, Wild, Sarah, Willemsen, Gonneke, Wright, Alan F., Yao, Jie, Thériault, Sébastien, Conen, David, Attia, John, Sever, Peter, Debette, Stéphanie, Mook-Kanamori, Dennis O., Zeggini, Eleftheria, Spector, Tim D., van der Harst, Pim, Palmer, Colin N.A., Vergnaud, Anne-Claire, Loos, Ruth J.F., Polasek, Ozren, Starr, John M., Girotto, Giorgia, Hayward, Caroline, Kooner, Jaspal S., Lindgren, Cecila M., Vitart, Veronique, Samani, Nilesh J., Tuomilehto, Jaakko, Gyllensten, Ulf, Knekt, Paul, Deary, Ian J., Ciullo, Marina, Elosua, Roberto, Keavney, Bernard D., Hicks, Andrew A., Scott, Robert A., Gasparini, Paolo, Laan, Maris, Liu, YongMei, Watkins, Hugh, Hartman, Catharina A., Salomaa, Veikko, Toniolo, Daniela, Perola, Markus, Wilson, James F., Schmidt, Helena, Zhao, Jing Hua, Lehtimäki, Terho, van Duijn, Cornelia M., Gudnason, Vilmundur, Psaty, Bruce M., Peters, Annette, Rettig, Rainer, James, Alan, Jukema, J. Wouter, Strachan, David P., Palmas, Walter, Metspalu, Andres, Ingelsson, Erik, Boomsma, Dorret I., Franco, Oscar H., Bochud, Murielle, Newton-Cheh, Christopher, Munroe, Patricia B., Elliott, Paul, Chasman, Daniel I., Chakravarti, Aravinda, Knight, Joanne, Morris, Andrew P., Levy, Daniel, Tobin, Martin D., Snieder, Harold, Caulfield, Mark J., and Ehret, Georg B.
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- 2017
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113. The red meat allergy syndrome in Sweden
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Apostolovic, Danijela, Tran, Thi Anh Thu, Starkhammar, Maria, Sánchez-Vidaurre, Sara, Hamsten, Carl, and Van Hage, Marianne
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- 2016
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114. Genome-wide association study for circulating levels of PAI-1 provides novel insights into its regulation
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Huang, Jie, Sabater-Lleal, Maria, Asselbergs, Folkert W., Tregouet, David, Shin, So-Youn, Ding, Jingzhong, Baumert, Jens, Oudot-Mellakh, Tiphaine, Folkersen, Lasse, Johnson, Andrew D., Smith, Nicholas L., Williams, Scott M., Ikram, Mohammad A., Kleber, Marcus E., Becker, Diane M., Truong, Vinh, Mychaleckyj, Josyf C., Tang, Weihong, Yang, Qiong, Sennblad, Bengt, Moore, Jason H., Williams, Frances M.K., Dehghan, Abbas, Silbernagel, Günther, Schrijvers, Elisabeth M.C., Smith, Shelly, Karakas, Mahir, Tofler, Geoffrey H., Silveira, Angela, Navis, Gerjan J., Lohman, Kurt, Chen, Ming-Huei, Peters, Annette, Goel, Anuj, Hopewell, Jemma C., Chambers, John C., Saleheen, Danish, Lundmark, Per, Psaty, Bruce M., Strawbridge, Rona J., Boehm, Bernhard O., Carter, Angela M., Meisinger, Christa, Peden, John F., Bis, Joshua C., McKnight, Barbara, Öhrvik, John, Taylor, Kent, Franzosi, Maria Grazia, Seedorf, Udo, Collins, Rory, Franco-Cereceda, Anders, Syvänen, Ann-Christine, Goodall, Alison H., Yanek, Lisa R., Cushman, Mary, Müller-Nurasyid, Martina, Folsom, Aaron R., Basu, Saonli, Matijevic, Nena, van Gilst, Wiek H., Kooner, Jaspal S., Hofman, Albert, Danesh, John, Clarke, Robert, Meigs, James B., Kathiresan, Sekar, Reilly, Muredach P., Klopp, Norman, Harris, Tamara B., Winkelmann, Bernhard R., Grant, Peter J., Hillege, Hans L., Watkins, Hugh, Spector, Timothy D., Becker, Lewis C., Tracy, Russell P., März, Winfried, Uitterlinden, Andre G., Eriksson, Per, Cambien, Francois, Morange, Pierre-Emmanuel, Koenig, Wolfgang, Soranzo, Nicole, van der Harst, Pim, Liu, Yongmei, O'Donnell, Christopher J., and Hamsten, Anders
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- 2012
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115. LDL oxidative modification and carotid atherosclerosis: Results of a multicenter study
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Nyyssönen, K., Kurl, S., Karppi, J., Nurmi, T., Baldassarre, D., Veglia, F., Rauramaa, R., de Faire, U., Hamsten, A., Smit, A.J., Mannarino, E., Humphries, S.E., Giral, P., Grossi, E., and Tremoli, E.
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- 2012
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116. Protein biomarkers for the prediction of cardiovascular disease in type 2 diabetes
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Looker, Helen C., Colombo, Marco, Agakov, Felix, Zeller, Tanja, Groop, Leif, Thorand, Barbara, Palmer, Colin N., Hamsten, Anders, de Faire, Ulf, Nogoceke, Everson, Livingstone, Shona J., Salomaa, Veikko, Leander, Karin, Barbarini, Nicola, Bellazzi, Riccardo, van Zuydam, Natalie, McKeigue, Paul M., Colhoun, Helen M., and on behalf of the SUMMIT Investigators
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- 2015
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117. Relationships of plasma factor VIIa-antithrombin complexes to manifest and future cardiovascular disease
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Silveira, Angela, Scanavini, Daniela, Boquist, Susanna, Ericsson, Carl-Göran, Hellénius, Mai-Lis, Leander, Karin, de Faire, Ulf, Öhrvik, John, Woodhams, Barry, Morrissey, James H., and Hamsten, Anders
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- 2012
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118. Serum 25-hydroxyvitamin D concentration, established and emerging cardiovascular risk factors and risk of myocardial infarction before the age of 60 years
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Deleskog, Anna, Piksasova, Olga, Silveira, Angela, Samnegård, Ann, Tornvall, Per, Eriksson, Per, Gustafsson, Sven, Östenson, Claes-Göran, Öhrvik, John, and Hamsten, Anders
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- 2012
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119. Comparison of HapMap and 1000 Genomes Reference Panels in a Large-Scale Genome-Wide Association Study.
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Paul S de Vries, Maria Sabater-Lleal, Daniel I Chasman, Stella Trompet, Tarunveer S Ahluwalia, Alexander Teumer, Marcus E Kleber, Ming-Huei Chen, Jie Jin Wang, John R Attia, Riccardo E Marioni, Maristella Steri, Lu-Chen Weng, Rene Pool, Vera Grossmann, Jennifer A Brody, Cristina Venturini, Toshiko Tanaka, Lynda M Rose, Christopher Oldmeadow, Johanna Mazur, Saonli Basu, Mattias Frånberg, Qiong Yang, Symen Ligthart, Jouke J Hottenga, Ann Rumley, Antonella Mulas, Anton J M de Craen, Anne Grotevendt, Kent D Taylor, Graciela E Delgado, Annette Kifley, Lorna M Lopez, Tina L Berentzen, Massimo Mangino, Stefania Bandinelli, Alanna C Morrison, Anders Hamsten, Geoffrey Tofler, Moniek P M de Maat, Harmen H M Draisma, Gordon D Lowe, Magdalena Zoledziewska, Naveed Sattar, Karl J Lackner, Uwe Völker, Barbara McKnight, Jie Huang, Elizabeth G Holliday, Mark A McEvoy, John M Starr, Pirro G Hysi, Dena G Hernandez, Weihua Guan, Fernando Rivadeneira, Wendy L McArdle, P Eline Slagboom, Tanja Zeller, Bruce M Psaty, André G Uitterlinden, Eco J C de Geus, David J Stott, Harald Binder, Albert Hofman, Oscar H Franco, Jerome I Rotter, Luigi Ferrucci, Tim D Spector, Ian J Deary, Winfried März, Andreas Greinacher, Philipp S Wild, Francesco Cucca, Dorret I Boomsma, Hugh Watkins, Weihong Tang, Paul M Ridker, Jan W Jukema, Rodney J Scott, Paul Mitchell, Torben Hansen, Christopher J O'Donnell, Nicholas L Smith, David P Strachan, and Abbas Dehghan
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Medicine ,Science - Abstract
An increasing number of genome-wide association (GWA) studies are now using the higher resolution 1000 Genomes Project reference panel (1000G) for imputation, with the expectation that 1000G imputation will lead to the discovery of additional associated loci when compared to HapMap imputation. In order to assess the improvement of 1000G over HapMap imputation in identifying associated loci, we compared the results of GWA studies of circulating fibrinogen based on the two reference panels. Using both HapMap and 1000G imputation we performed a meta-analysis of 22 studies comprising the same 91,953 individuals. We identified six additional signals using 1000G imputation, while 29 loci were associated using both HapMap and 1000G imputation. One locus identified using HapMap imputation was not significant using 1000G imputation. The genome-wide significance threshold of 5×10-8 is based on the number of independent statistical tests using HapMap imputation, and 1000G imputation may lead to further independent tests that should be corrected for. When using a stricter Bonferroni correction for the 1000G GWA study (P-value < 2.5×10-8), the number of loci significant only using HapMap imputation increased to 4 while the number of loci significant only using 1000G decreased to 5. In conclusion, 1000G imputation enabled the identification of 20% more loci than HapMap imputation, although the advantage of 1000G imputation became less clear when a stricter Bonferroni correction was used. More generally, our results provide insights that are applicable to the implementation of other dense reference panels that are under development.
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- 2017
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120. IgE reactivity to α-Gal in relation to Lyme borreliosis.
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Ivar Tjernberg, Carl Hamsten, Danijela Apostolovic, and Marianne van Hage
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Medicine ,Science - Abstract
An association between tick bites, the development of immunoglobulin E (IgE) antibodies to galactose-α-1, 3-galactose (α-Gal) and red meat allergy has recently been reported. Here we wanted to elucidate the relation between tick exposure, IgE antibodies to α-Gal and Lyme borreliosis (LB).In the highly LB endemic area of Kalmar County, Sweden, serum samples and health inquiries from 518 blood donors were included. All sera were investigated for multiple IgG anti-Borrelia antibodies using a multiplex assay (recomBead, Mikrogen). In addition, three serially collected sera over a six month period from 148 patients with clinically defined erythema migrans (EM) were included. IgE antibodies against α-Gal were determined using ImmunoCAP (Thermo Fisher Scientific).In blood donors reporting previous LB (n = 124) IgE to α-Gal was found in 16%, while in donors denying previous LB but with multiple anti-Borrelia antibodies (n = 94; interpreted as asymptomatic LB) 10% were IgE α-Gal-positive. Finally, in donors without Borrelia antibodies denying previous LB (n = 300) 14% showed IgE to α-Gal. No significant difference in proportions among the groups were found. In EM patients, IgE to α-Gal was found in 32/148 (22%) at diagnosis, 31/148 (21%) after two-three months and 23/148 (16%) after six months. A significant reduction of proportion and level of IgE to α-Gal was found between the second and third sample (p
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- 2017
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121. NAMPT (visfatin) and AKT1 genetic variants associate with myocardial infarction
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Leander, Karin, Gigante, Bruna, Silveira, Angela, Vikström, Max, Hamsten, Anders, and Högberg, Johan
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- 2012
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122. Large-Scale Gene-Centric Meta-Analysis across 39 Studies Identifies Type 2 Diabetes Loci
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Saxena, Richa, Elbers, Clara C., Guo, Yiran, Peter, Inga, Gaunt, Tom R., Mega, Jessica L., Lanktree, Matthew B., Tare, Archana, Castillo, Berta Almoguera, Li, Yun R., Johnson, Toby, Bruinenberg, Marcel, Gilbert-Diamond, Diane, Rajagopalan, Ramakrishnan, Voight, Benjamin F., Balasubramanyam, Ashok, Barnard, John, Bauer, Florianne, Baumert, Jens, Bhangale, Tushar, Böhm, Bernhard O., Braund, Peter S., Burton, Paul R., Chandrupatla, Hareesh R., Clarke, Robert, Cooper-DeHoff, Rhonda M., Crook, Errol D., Davey-Smith, George, Day, Ian N., de Boer, Anthonius, de Groot, Mark C.H., Drenos, Fotios, Ferguson, Jane, Fox, Caroline S., Furlong, Clement E., Gibson, Quince, Gieger, Christian, Gilhuijs-Pederson, Lisa A., Glessner, Joseph T., Goel, Anuj, Gong, Yan, Grant, Struan F.A., Grobbee, Diederick E., Hastie, Claire, Humphries, Steve E., Kim, Cecilia E., Kivimaki, Mika, Kleber, Marcus, Meisinger, Christa, Kumari, Meena, Langaee, Taimour Y., Lawlor, Debbie A., Li, Mingyao, Lobmeyer, Maximilian T., Maitland-van der Zee, Anke-Hilse, Meijs, Matthijs F.L., Molony, Cliona M., Morrow, David A., Murugesan, Gurunathan, Musani, Solomon K., Nelson, Christopher P., Newhouse, Stephen J., O'Connell, Jeffery R., Padmanabhan, Sandosh, Palmen, Jutta, Patel, Sanjey R., Pepine, Carl J., Pettinger, Mary, Price, Thomas S., Rafelt, Suzanne, Ranchalis, Jane, Rasheed, Asif, Rosenthal, Elisabeth, Ruczinski, Ingo, Shah, Sonia, Shen, Haiqing, Silbernagel, Günther, Smith, Erin N., Spijkerman, Annemieke W.M., Stanton, Alice, Steffes, Michael W., Thorand, Barbara, Trip, Mieke, van der Harst, Pim, van der A, Daphne L., van Iperen, Erik P.A., van Setten, Jessica, van Vliet-Ostaptchouk, Jana V., Verweij, Niek, Wolffenbuttel, Bruce H.R., Young, Taylor, Zafarmand, M. Hadi, Zmuda, Joseph M., Boehnke, Michael, Altshuler, David, McCarthy, Mark, Kao, W.H. Linda, Pankow, James S., Cappola, Thomas P., Sever, Peter, Poulter, Neil, Caulfield, Mark, Dominiczak, Anna, Shields, Denis C., Bhatt, Deepak L., Zhang, Li, Curtis, Sean P., Danesh, John, Casas, Juan P., van der Schouw, Yvonne T., Onland-Moret, N. Charlotte, Doevendans, Pieter A., Dorn, Gerald W., II, Farrall, Martin, FitzGerald, Garret A., Hamsten, Anders, Hegele, Robert, Hingorani, Aroon D., Hofker, Marten H., Huggins, Gordon S., Illig, Thomas, Jarvik, Gail P., Johnson, Julie A., Klungel, Olaf H., Knowler, William C., Koenig, Wolfgang, März, Winfried, Meigs, James B., Melander, Olle, Munroe, Patricia B., Mitchell, Braxton D., Bielinski, Susan J., Rader, Daniel J., Reilly, Muredach P., Rich, Stephen S., Rotter, Jerome I., Saleheen, Danish, Samani, Nilesh J., Schadt, Eric E., Shuldiner, Alan R., Silverstein, Roy, Kottke-Marchant, Kandice, Talmud, Philippa J., Watkins, Hugh, Asselbergs, Folkert W., de Bakker, Paul I.W., McCaffery, Jeanne, Wijmenga, Cisca, Sabatine, Marc S., Wilson, James G., Reiner, Alex, Bowden, Donald W., Hakonarson, Hakon, Siscovick, David S., and Keating, Brendan J.
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- 2012
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123. Antibody-based Protein Profiling of the Human Chromosome 21
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Uhlén, Mathias, Oksvold, Per, Älgenäs, Cajsa, Hamsten, Carl, Fagerberg, Linn, Klevebring, Daniel, Lundberg, Emma, Odeberg, Jacob, Pontén, Fredrik, Kondo, Tadashi, and Sivertsson, Åsa
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- 2012
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124. Genome-wide association study of circulating interleukin 6 levels identifies novel loci
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Martina Müller-Nurasyid, Jerome I. Rotter, David M. Evans, John P. Kemp, Emelia J. Benjamin, Graciela E. Delgado, Vilmundur Gudnason, Ann Hammarstedt, Panos Deloukas, Aroon D. Hingorani, Riccardo E. Marioni, David Stacey, Jenny van Dongen, Eric Boerwinkle, Joachim Heinrich, Yongmei Liu, S. Goya Wannamethee, Delilah Zabaneh, Braxton D. Mitchell, Marie Standl, Jackie F. Price, Maria G. Stathopoulou, Yoav Ben-Shlomo, Joris Deelen, Eero Kajantie, Mohammadreza Abdollahi, Christie M. Ballantyne, Johan G. Eriksson, Ilkka Seppälä, Elnaz Naderi, Barbara J. Jefferis, Richard W Morris, Nicholas J. Timpson, George Dedoussis, Sirpa Jalkanen, Mika Kivimäki, Perminder S. Sachdev, Diana van Heemst, Melanie Waldenberger, Gaurav Singhal, Elisabeth Thiering, Olli T. Raitakari, Anders Hamsten, Zoltán Kutalik, L. Bain, Eco J. C. de Geus, Tarunveer S. Ahluwalia, Yuri Milaneschi, Hubert Scharnagl, Juan P. Casas, Georg Homuth, Claes Ohlsson, Abbas Dehghan, Nicola J. Armstrong, Behrooz Z. Alizadeh, Terho Lehtimäki, Steve E. Humphries, Naveed Sattar, Bram P. Prins, Peter Rossing, Sophie Visvikis-Siest, Joana A. Revez, Ilja M. Nolte, Stella Trompet, Harold Snieder, Marian Beekman, Diana Marek, Beate St Pourcain, Thorkild I. A. Sørensen, Silvia Naitza, Karen A. Mather, Uwe Völker, Eline Slagboom, Tina Shah, Magdalene C. Jawahar, Jens Baumert, Alexander Teumer, Dorret I. Boomsma, Marcus E. Kleber, Peter Vollenweider, Wolfgang Koenig, Brenda W.J.H. Penninx, Kenneth Rice, Ian J. Deary, Pedro Marques-Vidal, Donna K. Arnett, Eleonora Porcu, Jouke-Jan Hottenga, Maria Sabater-Lleal, Bruce M. Psaty, Matthias Nauck, Dan Mellström, Joel Eriksson, Bernhard T. Baune, Debbie A Lawlor, Catherine Toben, Peter H. Whincup, Toshiko Tanaka, Stavroula Kanoni, Katri Räikkönen, Gonneke Willemsen, Bengt Sennblad, Julian N. Trollor, Yalda Jamshidi, Sarah E. Harris, Jari Lahti, Joshua C. Bis, Peter Durda, Yen Pei C. Chang, Jorgen Engmann, Tom R. Gaunt, Stella Aslibekyan, Anbupalam Thalamuthu, Mary F. Feitosa, Angela Silveira, Tine Jess, Stela McLachlan, J. Wouter Jukema, Chen Lu, Simon P. Mooijaart, Tim D. Spector, Harald Grallert, Winfried März, Alexandros M. Petrelis, Manuel A. R. Ferreira, Meena Kumari, Stochastics, Biological Psychology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, APH - Mental Health, APH - Methodology, CHARGE Inflammation Working Group, Epidemiology, Tampere University, Department of Clinical Chemistry, Clinical Medicine, Steno Diabetes Center, University of Copenhagen = Københavns Universitet (KU), University of Groningen [Groningen], Murdoch University, University of Alabama at Birmingham [ Birmingham] (UAB), QIMR Berghofer Medical Research Institute, University College of London [London] (UCL), Helmholtz-Zentrum München (HZM), Leiden University Medical Center (LUMC), University of Bristol [Bristol], University of Washington [Seattle], University of Maryland School of Medicine, University of Maryland System, Vrije Universiteit Amsterdam [Amsterdam] (VU), VU University Medical Center [Amsterdam], University of Heidelberg, Medical Faculty, Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL), Sahlgrenska Academy at University of Gothenburg [Göteborg], National Institute for Health and Welfare [Helsinki], University of Helsinki, William Harvey Research Institute, Barts and the London Medical School, University of Queensland [Brisbane], School of Public Health [Boston], Boston University [Boston] (BU), MRC Institute of Genetics and Molecular Medicine [Edinburgh] (IGMM), University of Edinburgh-Medical Research Council, University of Edinburgh, Amsterdam UMC, Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche [Roma] (CNR), Karolinska Institutet [Stockholm], University of Tampere [Finland], Adelaide Medical School [Australia], University of Adelaide, Universität Greifswald - University of Greifswald, University of New South Wales [Sydney] (UNSW), Prince of Wales Hospital, Ludwig-Maximilians-Universität München (LMU), Baylor College of Medicine (BCM), Baylor University, Boston University School of Medicine (BUSM), VA Boston Healthcare System, Harokopio University of Athens, Max planck Institute for Biology of Ageing [Cologne], Larner College of Medicine [University of Vermont, Burlington], University of Vermont [Burlington], Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Interfaculty Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt-Universität Greifswald, University of Turku, St George's, University of London, Statens Serum Institut [Copenhagen], Medical Faculty [Mannheim], Wake Forest School of Medicine [Winston-Salem], Wake Forest Baptist Medical Center, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Johannes Gutenberg - Universität Mainz (JGU), Vrije Universiteit Medical Centre (VUMC), British Heart Foundation Glasgow Cardiovascular Research Centre (BHF GCRC), University of Glasgow-NHS Greater Glasgow and Clyde, Medical University Graz, Uppsala Universitet [Uppsala], Max Planck Institute for Psycholinguistics, Max-Planck-Gesellschaft, Donders Institute for Brain, Cognition and Behaviour, Radboud university [Nijmegen], University of Kentucky, Melbourne Medical School [Melbourne], Faculty of Medicine, Dentistry and Health Sciences [Melbourne], University of Melbourne-University of Melbourne, University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), University of Maryland [Baltimore], Queen Mary University of London (QMUL), University of Iceland [Reykjavik], Ludwig Maximilian University [Munich] (LMU), Melbourne School of Population and Global Health [Melbourne], University of Melbourne, Deutsches Herzzentrum München (DHM), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), University of Ulm (UUlm), University of Essex, Greifswald University Hospital, Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), King‘s College London, University of Cambridge [UK] (CAM), Harbor UCLA Medical Center [Torrance, Ca.], Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Texas Health Science Center, The University of Texas Health Science Center at Houston (UTHealth), Human Genome Sequencing Center [Houston] (HGSC), Baylor University-Baylor University, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, HUS Children and Adolescents, Lastentautien yksikkö, Children's Hospital, Clinicum, Department of Bacteriology and Immunology, Department of Public Health, Department of Psychology and Logopedics, Research Programs Unit, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, Doctoral Programme in Human Behaviour, Life Course Epidemiology (LCE), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)
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AcademicSubjects/SCI01140 ,[SDV]Life Sciences [q-bio] ,Genome-wide association study ,030204 cardiovascular system & hematology ,DISEASE ,Pathogenesis ,Cohort Studies ,0302 clinical medicine ,cytokine ,SYSTEMIC-LUPUS-ERYTHEMATOSUS ,Association Studies Article ,ComputingMilieux_MISCELLANEOUS ,Genetics (clinical) ,Genetics ,0303 health sciences ,ARCHITECTURE ,CHRONIC INFLAMMATION ,1184 Genetics, developmental biology, physiology ,General Medicine ,RECEPTOR IL-6R GENE ,C-REACTIVE PROTEIN ,hla-drb1 gene ,3. Good health ,Medical genetics ,Medical Genetics ,chromosomes ,medicine.medical_specialty ,SUSCEPTIBILITY LOCI ,European Continental Ancestry Group ,Locus (genetics) ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,anti-inflammatory agents ,White People ,03 medical and health sciences ,medicine ,Humans ,Genetic Predisposition to Disease ,Interleukin 6 ,Molecular Biology ,Medicinsk genetik ,030304 developmental biology ,PRODUCE IL-6 ,Interleukin-6 ,Chromosome ,Receptors, Interleukin-6 ,RHEUMATOID-ARTHRITIS ,Interleukin 1 Receptor Antagonist Protein ,Gene Expression Regulation ,Genetic Loci ,CELLS ,biology.protein ,1182 Biochemistry, cell and molecular biology ,Human genome ,3111 Biomedicine ,Genome-Wide Association Study ,HLA-DRB1 Chains ,Interleukin-1 - Abstract
Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67 428 (ndiscovery = 52 654 and nreplication = 14 774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (Pcombined = 1.8 × 10−11), HLA-DRB1/DRB5 rs660895 on Chr6p21 (Pcombined = 1.5 × 10−10) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (Pcombined = 1.2 × 10−122). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.
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- 2021
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125. Correction: The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study.
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Thomas W Winkler, Anne E Justice, Mariaelisa Graff, Llilda Barata, Mary F Feitosa, Su Chu, Jacek Czajkowski, Tõnu Esko, Tove Fall, Tuomas O Kilpeläinen, Yingchang Lu, Reedik Mägi, Evelin Mihailov, Tune H Pers, Sina Rüeger, Alexander Teumer, Georg B Ehret, Teresa Ferreira, Nancy L Heard-Costa, Juha Karjalainen, Vasiliki Lagou, Anubha Mahajan, Michael D Neinast, Inga Prokopenko, Jeannette Simino, Tanya M Teslovich, Rick Jansen, Harm-Jan Westra, Charles C White, Devin Absher, Tarunveer S Ahluwalia, Shafqat Ahmad, Eva Albrecht, Alexessander Couto Alves, Jennifer L Bragg-Gresham, Anton J M de Craen, Joshua C Bis, Amélie Bonnefond, Gabrielle Boucher, Gemma Cadby, Yu-Ching Cheng, Charleston W K Chiang, Graciela Delgado, Ayse Demirkan, Nicole Dueker, Niina Eklund, Gudny Eiriksdottir, Joel Eriksson, Bjarke Feenstra, Krista Fischer, Francesca Frau, Tessel E Galesloot, Frank Geller, Anuj Goel, Mathias Gorski, Tanja B Grammer, Stefan Gustafsson, Saskia Haitjema, Jouke-Jan Hottenga, Jennifer E Huffman, Anne U Jackson, Kevin B Jacobs, Åsa Johansson, Marika Kaakinen, Marcus E Kleber, Jari Lahti, Irene Mateo Leach, Benjamin Lehne, Youfang Liu, Ken Sin Lo, Mattias Lorentzon, Jian'an Luan, Pamela A F Madden, Massimo Mangino, Barbara McKnight, Carolina Medina-Gomez, Keri L Monda, May E Montasser, Gabriele Müller, Martina Müller-Nurasyid, Ilja M Nolte, Kalliope Panoutsopoulou, Laura Pascoe, Lavinia Paternoster, Nigel W Rayner, Frida Renström, Federica Rizzi, Lynda M Rose, Kathy A Ryan, Perttu Salo, Serena Sanna, Hubert Scharnagl, Jianxin Shi, Albert Vernon Smith, Lorraine Southam, Alena Stančáková, Valgerdur Steinthorsdottir, Rona J Strawbridge, Yun Ju Sung, Ioanna Tachmazidou, Toshiko Tanaka, Gudmar Thorleifsson, Stella Trompet, Natalia Pervjakova, Jonathan P Tyrer, Liesbeth Vandenput, Sander W van der Laan, Nathalie van der Velde, Jessica van Setten, Jana V van Vliet-Ostaptchouk, Niek Verweij, Efthymia Vlachopoulou, Lindsay L Waite, Sophie R Wang, Zhaoming Wang, Sarah H Wild, Christina Willenborg, James F Wilson, Andrew Wong, Jian Yang, Loïc Yengo, Laura M Yerges-Armstrong, Lei Yu, Weihua Zhang, Jing Hua Zhao, Ehm A Andersson, Stephan J L Bakker, Damiano Baldassarre, Karina Banasik, Matteo Barcella, Cristina Barlassina, Claire Bellis, Paola Benaglio, John Blangero, Matthias Blüher, Fabrice Bonnet, Lori L Bonnycastle, Heather A Boyd, Marcel Bruinenberg, Aron S Buchman, Harry Campbell, Yii-Der Ida Chen, Peter S Chines, Simone Claudi-Boehm, John Cole, Francis S Collins, Eco J C de Geus, Lisette C P G M de Groot, Maria Dimitriou, Jubao Duan, Stefan Enroth, Elodie Eury, Aliki-Eleni Farmaki, Nita G Forouhi, Nele Friedrich, Pablo V Gejman, Bruna Gigante, Nicola Glorioso, Alan S Go, Omri Gottesman, Jürgen Gräßler, Harald Grallert, Niels Grarup, Yu-Mei Gu, Linda Broer, Annelies C Ham, Torben Hansen, Tamara B Harris, Catharina A Hartman, Maija Hassinen, Nicholas Hastie, Andrew T Hattersley, Andrew C Heath, Anjali K Henders, Dena Hernandez, Hans Hillege, Oddgeir Holmen, Kees G Hovingh, Jennie Hui, Lise L Husemoen, Nina Hutri-Kähönen, Pirro G Hysi, Thomas Illig, Philip L De Jager, Shapour Jalilzadeh, Torben Jørgensen, J Wouter Jukema, Markus Juonala, Stavroula Kanoni, Maria Karaleftheri, Kay Tee Khaw, Leena Kinnunen, Steven J Kittner, Wolfgang Koenig, Ivana Kolcic, Peter Kovacs, Nikolaj T Krarup, Wolfgang Kratzer, Janine Krüger, Diana Kuh, Meena Kumari, Theodosios Kyriakou, Claudia Langenberg, Lars Lannfelt, Chiara Lanzani, Vaneet Lotay, Lenore J Launer, Karin Leander, Jaana Lindström, Allan Linneberg, Yan-Ping Liu, Stéphane Lobbens, Robert Luben, Valeriya Lyssenko, Satu Männistö, Patrik K Magnusson, Wendy L McArdle, Cristina Menni, Sigrun Merger, Lili Milani, Grant W Montgomery, Andrew P Morris, Narisu Narisu, Mari Nelis, Ken K Ong, Aarno Palotie, Louis Pérusse, Irene Pichler, Maria G Pilia, Anneli Pouta, Myriam Rheinberger, Rasmus Ribel-Madsen, Marcus Richards, Kenneth M Rice, Treva K Rice, Carlo Rivolta, Veikko Salomaa, Alan R Sanders, Mark A Sarzynski, Salome Scholtens, Robert A Scott, William R Scott, Sylvain Sebert, Sebanti Sengupta, Bengt Sennblad, Thomas Seufferlein, Angela Silveira, P Eline Slagboom, Jan H Smit, Thomas H Sparsø, Kathleen Stirrups, Ronald P Stolk, Heather M Stringham, Morris A Swertz, Amy J Swift, Ann-Christine Syvänen, Sian-Tsung Tan, Barbara Thorand, Anke Tönjes, Angelo Tremblay, Emmanouil Tsafantakis, Peter J van der Most, Uwe Völker, Marie-Claude Vohl, Judith M Vonk, Melanie Waldenberger, Ryan W Walker, Roman Wennauer, Elisabeth Widén, Gonneke Willemsen, Tom Wilsgaard, Alan F Wright, M Carola Zillikens, Suzanne C van Dijk, Natasja M van Schoor, Folkert W Asselbergs, Paul I W de Bakker, Jacques S Beckmann, John Beilby, David A Bennett, Richard N Bergman, Sven Bergmann, Carsten A Böger, Bernhard O Boehm, Eric Boerwinkle, Dorret I Boomsma, Stefan R Bornstein, Erwin P Bottinger, Claude Bouchard, John C Chambers, Stephen J Chanock, Daniel I Chasman, Francesco Cucca, Daniele Cusi, George Dedoussis, Jeanette Erdmann, Johan G Eriksson, Denis A Evans, Ulf de Faire, Martin Farrall, Luigi Ferrucci, Ian Ford, Lude Franke, Paul W Franks, Philippe Froguel, Ron T Gansevoort, Christian Gieger, Henrik Grönberg, Vilmundur Gudnason, Ulf Gyllensten, Per Hall, Anders Hamsten, Pim van der Harst, Caroline Hayward, Markku Heliövaara, Christian Hengstenberg, Andrew A Hicks, Aroon Hingorani, Albert Hofman, Frank Hu, Heikki V Huikuri, Kristian Hveem, Alan L James, Joanne M Jordan, Antti Jula, Mika Kähönen, Eero Kajantie, Sekar Kathiresan, Lambertus A L M Kiemeney, Mika Kivimaki, Paul B Knekt, Heikki A Koistinen, Jaspal S Kooner, Seppo Koskinen, Johanna Kuusisto, Winfried Maerz, Nicholas G Martin, Markku Laakso, Timo A Lakka, Terho Lehtimäki, Guillaume Lettre, Douglas F Levinson, Lars Lind, Marja-Liisa Lokki, Pekka Mäntyselkä, Mads Melbye, Andres Metspalu, Braxton D Mitchell, Frans L Moll, Jeffrey C Murray, Arthur W Musk, Markku S Nieminen, Inger Njølstad, Claes Ohlsson, Albertine J Oldehinkel, Ben A Oostra, Lyle J Palmer, James S Pankow, Gerard Pasterkamp, Nancy L Pedersen, Oluf Pedersen, Brenda W Penninx, Markus Perola, Annette Peters, Ozren Polašek, Peter P Pramstaller, Bruce M Psaty, Lu Qi, Thomas Quertermous, Olli T Raitakari, Tuomo Rankinen, Rainer Rauramaa, Paul M Ridker, John D Rioux, Fernando Rivadeneira, Jerome I Rotter, Igor Rudan, Hester M den Ruijter, Juha Saltevo, Naveed Sattar, Heribert Schunkert, Peter E H Schwarz, Alan R Shuldiner, Juha Sinisalo, Harold Snieder, Thorkild I A Sørensen, Tim D Spector, Jan A Staessen, Bandinelli Stefania, Unnur Thorsteinsdottir, Michael Stumvoll, Jean-Claude Tardif, Elena Tremoli, Jaakko Tuomilehto, André G Uitterlinden, Matti Uusitupa, André L M Verbeek, Sita H Vermeulen, Jorma S Viikari, Veronique Vitart, Henry Völzke, Peter Vollenweider, Gérard Waeber, Mark Walker, Henri Wallaschofski, Nicholas J Wareham, Hugh Watkins, Eleftheria Zeggini, arcOGEN Consortium, CHARGE Consortium, DIAGRAM Consortium, GLGC Consortium, Global-BPGen Consortium, ICBP Consortium, MAGIC Consortium, Aravinda Chakravarti, Deborah J Clegg, L Adrienne Cupples, Penny Gordon-Larsen, Cashell E Jaquish, D C Rao, Goncalo R Abecasis, Themistocles L Assimes, Inês Barroso, Sonja I Berndt, Michael Boehnke, Panos Deloukas, Caroline S Fox, Leif C Groop, David J Hunter, Erik Ingelsson, Robert C Kaplan, Mark I McCarthy, Karen L Mohlke, Jeffrey R O'Connell, David Schlessinger, David P Strachan, Kari Stefansson, Cornelia M van Duijn, Joel N Hirschhorn, Cecilia M Lindgren, Iris M Heid, Kari E North, Ingrid B Borecki, Zoltán Kutalik, and Ruth J F Loos
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Genetics ,QH426-470 - Abstract
[This corrects the article DOI: 10.1371/journal.pgen.1005378.].
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- 2016
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126. Increased expression of leukotriene C₄ synthase and predominant formation of cysteinyl-leukotrienes in human abdominal aortic aneurysm
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Di Gennaro, Antonio, Wågsäter, Dick, Mäyränpää, Mikko I., Gabrielsen, Anders, Swedenborg, Jesper, Hamsten, Anders, Samuelsson, Bengt, Eriksson, Per, and Haeggström, Jesper Z.
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- 2010
127. Plasma lecithin:cholesterol acyltransferase and carotid intima-media thickness in European individuals at high cardiovascular risk
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Laura Calabresi, Damiano Baldassarre, Sara Simonelli, Monica Gomaraschi, Mauro Amato, Samuela Castelnuovo, Beatrice Frigerio, Alessio Ravani, Daniela Sansaro, Jussi Kauhanen, Rainer Rauramaa, Ulf de Faire, Anders Hamsten, Andries J. Smit, Elmo Mannarino, Steve E. Humphries, Philippe Giral, Fabrizio Veglia, Cesare R. Sirtori, Guido Franceschini, and Elena Tremoli
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atherosclerosis ,cardiovascular disease ,high density lipoproteins ,Biochemistry ,QD415-436 - Abstract
Lecithin:cholesterol acyltransferase (LCAT) is the enzyme responsible for cholesterol esterification in plasma. LCAT is a major factor in HDL remodeling and metabolism, and it has long been believed to play a critical role in macrophage reverse cholesterol transport (RCT). The effect of LCAT on human atherogenesis is still controversial. In the present study, the plasma LCAT concentration was measured in all subjects (n = 540) not on drug treatment at the time of enrollment in the multicenter, longitudinal, observational IMPROVE study. Mean and maximum intima-media thickness (IMT) of the whole carotid tree was measured by B-mode ultrasonography in all subjects. In the entire cohort, LCAT quartiles were not associated with carotid mean and maximum IMT (P for trend 0.95 and 0.18, respectively), also after adjustment for age, gender, HDL-cholesterol (HDL-C), and triglycerides. No association between carotid IMT and LCAT quartiles was observed in men (P=0.30 and P=0.99 for mean and maximum IMT, respectively), whereas carotid IMT increased with LCAT quartiles in women (P for trend 0.14 and 0.019 for mean and maximum IMT, respectively). The present findings support the concept that LCAT is not required for an efficient reverse cholesterol transport and that a low plasma LCAT concentration and activity is not associated with increased atherosclerosis.
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- 2011
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128. This title is unavailable for guests, please login to see more information.
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Kiewiet, Mensiena B. G., Peruško, Marija, Grundström, Jeanette, Hamsten, Carl, Starkhammar, Maria, Apostolović, Danijela, van Hage, Marianne, Kiewiet, Mensiena B. G., Peruško, Marija, Grundström, Jeanette, Hamsten, Carl, Starkhammar, Maria, Apostolović, Danijela, and van Hage, Marianne
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- 2022
129. Cohort profile : the Swedish Maternal Microbiome project (SweMaMi) - assessing the dynamic associations between the microbiome and maternal and neonatal adverse events
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Fransson, Emma, Gudnadottir, Unnur, Hugerth, Luisa W., Itzel, Eva Wiberg, Hamsten, Marica, Boulund, Fredrik, Pennhag, Alexandra, Du, Juan, Schuppe-Koistinen, Ina, Brusselaers, Nele, Engstrand, Lars, Fransson, Emma, Gudnadottir, Unnur, Hugerth, Luisa W., Itzel, Eva Wiberg, Hamsten, Marica, Boulund, Fredrik, Pennhag, Alexandra, Du, Juan, Schuppe-Koistinen, Ina, Brusselaers, Nele, and Engstrand, Lars
- Abstract
Purpose The Swedish Maternal Microbiome (SweMaMi) project was initiated to better understand the dynamics of the microbiome in pregnancy, with longitudinal microbiome sampling, shotgun metagenomics, extensive questionnaires and health registry linkage. Participants Pregnant women were recruited before the 20th gestational week during 2017-2021 in Sweden. In total, 5439 pregnancies (5193 unique women) were included. For 3973 pregnancies (73%), samples were provided at baseline, and for 3141 (58%) at all three timepoints (second and third trimester and postpartum). In total, 38 591 maternal microbiome samples (vaginal, faecal and saliva) and 3109 infant faecal samples were collected. Questionnaires were used to collect information on general, reproductive and mental health, diet and lifestyle, complemented by linkage to the nationwide health registries, also used to follow up the health of the offspring (up to age 10). Findings to date The cohort is fairly representative for the total Swedish pregnant population (data from 2019), with 41% first-time mothers. Women with university level education, born in Sweden, with normal body mass index, not using tobacco-products and aged 30-34 years were slightly over-represented. Future plans The sample and data collection were finalised in November 2021. The next steps are the characterisation of the microbial DNA and linkage to the health and demographic information from the questionnaires and registries. The role of the microbiome on maternal and neonatal outcomes and early-childhood diseases will be explored (including preterm birth, miscarriage) and the role and interaction of other risk factors and confounders (including endometriosis, polycystic ovarian syndrome, diet, drug use). This is currently among the largest pregnancy cohorts in the world with longitudinal design and detailed and standardised microbiome sampling enabling follow-up of both mothers and children. The findings are expected to contribute greatly to the
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- 2022
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130. The microbiome in reproductive health: protocol for a systems biology approach using a prospective, observational study design
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Krog, Maria Christine, Madsen, Mette Elkjær, Bliddal, Sofie, Bashir, Zahra, Vexø, Laura Emilie, Hartwell, Dorthe, Hugerth, Luisa W, Fransson, Emma, Hamsten, Marica, Boulund, Fredrik, Wannerberger, Kristin, Engstrand, Lars, Schuppe-Koistinen, Ina, Nielsen, Henriette Svarre, Krog, Maria Christine, Madsen, Mette Elkjær, Bliddal, Sofie, Bashir, Zahra, Vexø, Laura Emilie, Hartwell, Dorthe, Hugerth, Luisa W, Fransson, Emma, Hamsten, Marica, Boulund, Fredrik, Wannerberger, Kristin, Engstrand, Lars, Schuppe-Koistinen, Ina, and Nielsen, Henriette Svarre
- Abstract
STUDY QUESTION What is the microbiome profile across different body sites in relation to the normal menstrual cycle (with and without hormonal contraception), recurrent pregnancy loss (RPL) (before and during pregnancy, pregnancy loss or birth) and endometriosis (before, during and after surgery)? How do these profiles interact with genetics, environmental exposures, immunological and endocrine biomarkers? WHAT IS KNOWN ALREADY The microbiome is a key factor influencing human health and disease in areas as diverse as immune functioning, gastrointestinal disease and mental and metabolic disorders. There is mounting evidence to suggest that the reproductive microbiome may be influential in general and reproductive health, fertility and pregnancy outcomes. STUDY DESIGN, SIZE, DURATION This is a prospective, longitudinal, observational study using a systems biology approach in three cohorts totalling 920 participants. Since microbiome profiles by shot-gun sequencing have never been investigated in healthy controls during varying phases of the menstrual cycle, patients with RPL and patients with endometriosis, no formal sample size calculation can be performed. The study period is from 2017 to 2024 and allows for longitudinal profiling of study participants to enable deeper understanding of the role of the microbiome and of host–microbe interactions in reproductive health. PARTICIPANTS/MATERIALS, SETTING, METHODS Participants in each cohort are as follows: Part 1 MiMens—150 healthy women with or without hormonal contraception; Part 2 MiRPL—200 couples with RPL, 50 healthy couples with prior uncomplicated pregnancy and 150 newborns; Part 3 MiEndo—120 patients with endometriosis requiring surgery with or without hormonal treatment. Microbiome profiles from saliva, faeces, rectal mucosa, vaginal fluid and endometrium will be studied, as well as the Omics profile, endocrine disrupting chemicals and endocrine and immune factors in blood, hair, saliva and urine. Pregnancy loss
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- 2022
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131. Stroke genetics informs drug discovery and risk prediction across ancestries
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Mishra, A, Malik, R, Hachiya, T, Jurgenson, T, Namba, S, Posner, DC, Kamanu, FK, Koido, M, Le Grand, Q, Shi, M, He, Y, Georgakis, MK, Caro, I, Krebs, K, Liaw, Y-C, Vaura, FC, Lin, K, Winsvold, BS, Srinivasasainagendra, V, Parodi, L, Bae, H-J, Chauhan, G, Chong, MR, Tomppo, L, Akinyemi, R, Roshchupkin, GV, Habib, N, Jee, YH, Thomassen, JQ, Abedi, V, Carcel-Marquez, J, Nygaard, M, Leonard, HL, Yang, C, Yonova-Doing, E, Knol, MJ, Lewis, AJ, Judy, RL, Ago, T, Amouyel, P, Armstrong, ND, Bakker, MK, Bartz, TM, Bennett, DA, Bis, JC, Bordes, C, Borte, S, Cain, A, Ridker, PM, Cho, K, Chen, Z, Cruchaga, C, Cole, JW, de Jager, PL, de Cid, R, Endres, M, Ferreira, LE, Geerlings, MI, Gasca, NC, Gudnason, V, Hata, J, He, J, Heath, AK, Ho, Y-L, Havulinna, AS, Hopewell, JC, Hyacinth, HI, Inouye, M, Jacob, MA, Jeon, CE, Jern, C, Kamouchi, M, Keene, KL, Kitazono, T, Kittner, SJ, Konuma, T, Kumar, A, Lacaze, P, Launer, LJ, Lee, K-J, Lepik, K, Li, J, Li, L, Manichaikul, A, Markus, HS, Marston, NA, Meitinger, T, Mitchell, BD, Montellano, FA, Morisaki, T, Mosley, TH, Nalls, MA, Nordestgaard, BG, O'Donnell, MJ, Okada, Y, Onland-Moret, NC, Ovbiagele, B, Peters, A, Psaty, BM, Rich, SS, Rosand, J, Sabatine, MS, Sacco, RL, Saleheen, D, Sandset, EC, Salomaa, V, Sargurupremraj, M, Sasaki, M, Satizabal, CL, Schmidt, CO, Shimizu, A, Smith, NL, Sloane, KL, Sutoh, Y, Sun, YV, Tanno, K, Tiedt, S, Tatlisumak, T, Torres-Aguila, NP, Tiwari, HK, Tregouet, D-A, Trompet, S, Tuladhar, AM, Tybjaerg-Hansen, A, van Vugt, M, Vibo, R, Verma, SS, Wiggins, KL, Wennberg, P, Woo, D, Wilson, PWF, Xu, H, Yang, Q, Yoon, K, Millwood, IY, Gieger, C, Ninomiya, T, Grabe, HJ, Jukema, JW, Rissanen, IL, Strbian, D, Kim, YJ, Chen, P-H, Mayerhofer, E, Howson, JMM, Irvin, MR, Adams, H, Wassertheil-Smoller, S, Christensen, K, Ikram, MA, Rundek, T, Worrall, BB, Lathrop, GM, Riaz, M, Simonsick, EM, Korv, J, Franca, PHC, Zand, R, Prasad, K, Frikke-Schmidt, R, de Leeuw, F-E, Liman, T, Haeusler, KG, Ruigrok, YM, Heuschmann, PU, Longstreth, WT, Jung, KJ, Bastarache, L, Pare, G, Damrauer, SM, Chasman, DI, Rotter, JI, Anderson, CD, Zwart, J-A, Niiranen, TJ, Fornage, M, Liaw, Y-P, Seshadri, S, Fernandez-Cadenas, I, Walters, RG, Ruff, CT, Owolabi, MO, Huffman, JE, Milani, L, Kamatani, Y, Dichgans, M, Debette, S, Lee, J-M, Cheng, Y-C, Meschia, JF, Chen, WM, Sale, MM, Zonderman, AB, Evans, MK, Wilson, JG, Correa, A, Traylor, M, Lewis, CM, Reiner, A, Haessler, J, Langefeld, CD, Gottesman, RF, Yaffe, K, Liu, YM, Kooperberg, C, Lange, LA, Furie, KL, Arnett, DK, Benavente, OR, Grewal, RP, Peddareddygari, LR, Hveem, K, Lindstrom, S, Wang, L, Smith, EN, Gordon, W, Vlieg, AVH, de Andrade, M, Brody, JA, Pattee, JW, Brumpton, BM, Suchon, P, Chen, M-H, Frazer, KA, Turman, C, Germain, M, MacDonald, J, Braekkan, SK, Armasu, SM, Pankratz, N, Jackson, RD, Nielsen, JB, Giulianin, F, Puurunen, MK, Ibrahim, M, Heckbert, SR, Bammler, TK, McCauley, BM, Taylor, KD, Pankow, JS, Reiner, AP, Gabrielsen, ME, Deleuze, J-F, O'Donnell, CJ, Kim, J, McKnight, B, Kraft, P, Hansen, J-B, Rosendaal, FR, Heit, JA, Tang, W, Morange, P-E, Johnson, AD, Kabrhel, C, van Dijk, EJ, Koudstaal, PJ, Luijckx, G-J, Nederkoorn, PJ, van Oostenbrugge, RJ, Visser, MC, Wermer, MJH, Kappelle, LJ, Esko, T, Metspalu, A, Magi, R, Nelis, M, Levi, CR, Maguire, J, Jimenez-Conde, J, Sharma, P, Sudlow, CLM, Rannikmae, K, Schmidt, R, Slowik, A, Pera, J, Thijs, VNS, Lindgren, AG, Ilinca, A, Melander, O, Engstrom, G, Rexrode, KM, Rothwell, PM, Stanne, TM, Johnson, JA, Danesh, J, Butterworth, AS, Heitsch, L, Boncoraglio, GB, Kubo, M, Pezzini, A, Rolfs, A, Giese, A-K, Weir, D, Ross, OA, Lemmons, R, Soderholm, M, Cushman, M, Jood, K, McDonough, CW, Bell, S, Linkohr, B, Lee, T-H, Putaala, J, Lopez, OL, Carty, CL, Jian, X, Schminke, U, Cullell, N, Delgado, P, Ibanez, L, Krupinski, J, Lioutas, V, Matsuda, K, Montaner, J, Muino, E, Roquer, J, Sarnowski, C, Sattar, N, Sibolt, G, Teumer, A, Rutten-Jacobs, L, Kanai, M, Gretarsdottir, S, Rost, NS, Yusuf, S, Almgren, P, Ay, H, Bevan, S, Brown, RD, Carrera, C, Buring, JE, Chen, W-M, Cotlarciuc, I, de Bakker, PIW, DeStefano, AL, den Hoed, M, Duan, Q, Engelter, ST, Falcone, GJ, Gustafsson, S, Hassan, A, Holliday, EG, Howard, G, Hsu, F-C, Ingelsson, E, Harris, TB, Kissela, BM, Kleindorfer, DO, Langenberg, C, Leys, D, Lin, W-Y, Lorentzen, E, Magnusson, PK, McArdle, PF, Pulit, SL, Rice, K, Sakaue, S, Sapkota, BR, Tanislav, C, Thorleifsson, G, Thorsteinsdottir, U, Tzourio, C, van Duijn, CM, Walters, M, Wareham, NJ, Amin, N, Aparicio, HJ, Attia, J, Beiser, AS, Berr, C, Bustamante, M, Caso, V, Choi, SH, Chowhan, A, Dartigues, J-F, Delavaran, H, Dorr, M, Ford, I, Gurpreet, WS, Hamsten, A, Hozawa, A, Ingelsson, M, Iwasaki, M, Kaffashian, S, Kalra, L, Kjartansson, O, Kloss, M, Labovitz, DL, Laurie, CC, Lind, L, Lindgren, CM, Makoto, H, Minegishi, N, Morris, AP, Mueller-Nurasyid, M, Norrving, B, Ogishima, S, Parati, EA, Pedersen, NL, Perola, M, Jousilahti, P, Pileggi, S, Rabionet, R, Riba-Llena, I, Ribases, M, Romero, JR, Rudd, AG, Sarin, A-P, Sarju, R, Satoh, M, Sawada, N, Sigurdsson, A, Smith, A, Stine, OC, Stott, DJ, Strauch, K, Takai, T, Tanaka, H, Touze, E, Tsugane, S, Uitterlinden, AG, Valdimarsson, EM, van der Lee, SJ, Wakai, K, Williams, SR, Wolfe, CDA, Wong, Q, Yamaji, T, Sanghera, DK, Stefansson, K, Martinez-Majander, N, Sobue, K, Soriano-Tarraga, C, Volzke, H, Akpa, O, Sarfo, FS, Akpalu, A, Obiako, R, Wahab, K, Osaigbovo, G, Owolabi, L, Komolafe, M, Jenkins, C, Arulogun, O, Ogbole, G, Adeoye, AM, Akinyemi, J, Agunloye, A, Fakunle, AG, Uvere, E, Olalere, A, Adebajo, OJ, Chen, J, Clarke, R, Collins, R, Guo, Y, Wang, C, Lv, J, Peto, R, Chen, Y, Fairhurst-Hunter, Z, Hill, M, Pozarickij, A, Schmidt, D, Stevens, B, Turnbull, I, Yu, C, Nagai, A, Murakami, Y, Shiroma, EJ, Sigurdsson, S, Ghanbari, M, Boerwinkle, E, Fongang, B, Wang, R, Ikram, MK, Volker, U, de Laat, KF, van Norden, AGW, de Kort, PL, Vermeer, SE, Brouwers, PJAM, Gons, RAR, den Heijer, T, van Dijk, GW, van Rooij, FGW, Aamodt, AH, Skogholt, AH, Willer, CJ, Heuch, I, Hagen, K, Fritsche, LG, Pedersen, LM, Ellekjaer, H, Zhou, W, Martinsen, AE, Kristoffersen, ES, Thomas, LF, Kleinschnitz, C, Frantz, S, Ungethum, K, Gallego-Fabrega, C, Lledos, M, Llucia-Carol, L, Sobrino, T, Campos, F, Castillo, J, Freijo, M, Arenillas, JF, Obach, V, Alvarez-Sabin, J, Molina, CA, Ribo, M, Munoz-Narbona, L, Lopez-Cancio, E, Millan, M, Diaz-Navarro, R, Vives-Bauza, C, Serrano-Heras, G, Segura, T, Dhar, R, Delgado-Mederos, R, Prats-Sanchez, L, Camps-Renom, P, Blay, N, Sumoy, L, Marti-Fabregas, J, Schnohr, P, Jensen, GB, Benn, M, Afzal, S, Kamstrup, PR, van Setten, J, van der Laan, SW, Vonk, JMJ, Kim, B-J, Curtze, S, Tiainen, M, Kinnunen, J, Menon, V, Sung, YJ, Saillour-Glenisson, F, Gravel, S, Mishra, A, Malik, R, Hachiya, T, Jurgenson, T, Namba, S, Posner, DC, Kamanu, FK, Koido, M, Le Grand, Q, Shi, M, He, Y, Georgakis, MK, Caro, I, Krebs, K, Liaw, Y-C, Vaura, FC, Lin, K, Winsvold, BS, Srinivasasainagendra, V, Parodi, L, Bae, H-J, Chauhan, G, Chong, MR, Tomppo, L, Akinyemi, R, Roshchupkin, GV, Habib, N, Jee, YH, Thomassen, JQ, Abedi, V, Carcel-Marquez, J, Nygaard, M, Leonard, HL, Yang, C, Yonova-Doing, E, Knol, MJ, Lewis, AJ, Judy, RL, Ago, T, Amouyel, P, Armstrong, ND, Bakker, MK, Bartz, TM, Bennett, DA, Bis, JC, Bordes, C, Borte, S, Cain, A, Ridker, PM, Cho, K, Chen, Z, Cruchaga, C, Cole, JW, de Jager, PL, de Cid, R, Endres, M, Ferreira, LE, Geerlings, MI, Gasca, NC, Gudnason, V, Hata, J, He, J, Heath, AK, Ho, Y-L, Havulinna, AS, Hopewell, JC, Hyacinth, HI, Inouye, M, Jacob, MA, Jeon, CE, Jern, C, Kamouchi, M, Keene, KL, Kitazono, T, Kittner, SJ, Konuma, T, Kumar, A, Lacaze, P, Launer, LJ, Lee, K-J, Lepik, K, Li, J, Li, L, Manichaikul, A, Markus, HS, Marston, NA, Meitinger, T, Mitchell, BD, Montellano, FA, Morisaki, T, Mosley, TH, Nalls, MA, Nordestgaard, BG, O'Donnell, MJ, Okada, Y, Onland-Moret, NC, Ovbiagele, B, Peters, A, Psaty, BM, Rich, SS, Rosand, J, Sabatine, MS, Sacco, RL, Saleheen, D, Sandset, EC, Salomaa, V, Sargurupremraj, M, Sasaki, M, Satizabal, CL, Schmidt, CO, Shimizu, A, Smith, NL, Sloane, KL, Sutoh, Y, Sun, YV, Tanno, K, Tiedt, S, Tatlisumak, T, Torres-Aguila, NP, Tiwari, HK, Tregouet, D-A, Trompet, S, Tuladhar, AM, Tybjaerg-Hansen, A, van Vugt, M, Vibo, R, Verma, SS, Wiggins, KL, Wennberg, P, Woo, D, Wilson, PWF, Xu, H, Yang, Q, Yoon, K, Millwood, IY, Gieger, C, Ninomiya, T, Grabe, HJ, Jukema, JW, Rissanen, IL, Strbian, D, Kim, YJ, Chen, P-H, Mayerhofer, E, Howson, JMM, Irvin, MR, Adams, H, Wassertheil-Smoller, S, Christensen, K, Ikram, MA, Rundek, T, Worrall, BB, Lathrop, GM, Riaz, M, Simonsick, EM, Korv, J, Franca, PHC, Zand, R, Prasad, K, Frikke-Schmidt, R, de Leeuw, F-E, Liman, T, Haeusler, KG, Ruigrok, YM, Heuschmann, PU, Longstreth, WT, Jung, KJ, Bastarache, L, Pare, G, Damrauer, SM, Chasman, DI, Rotter, JI, Anderson, CD, Zwart, J-A, Niiranen, TJ, Fornage, M, Liaw, Y-P, Seshadri, S, Fernandez-Cadenas, I, Walters, RG, Ruff, CT, Owolabi, MO, Huffman, JE, Milani, L, Kamatani, Y, Dichgans, M, Debette, S, Lee, J-M, Cheng, Y-C, Meschia, JF, Chen, WM, Sale, MM, Zonderman, AB, Evans, MK, Wilson, JG, Correa, A, Traylor, M, Lewis, CM, Reiner, A, Haessler, J, Langefeld, CD, Gottesman, RF, Yaffe, K, Liu, YM, Kooperberg, C, Lange, LA, Furie, KL, Arnett, DK, Benavente, OR, Grewal, RP, Peddareddygari, LR, Hveem, K, Lindstrom, S, Wang, L, Smith, EN, Gordon, W, Vlieg, AVH, de Andrade, M, Brody, JA, Pattee, JW, Brumpton, BM, Suchon, P, Chen, M-H, Frazer, KA, Turman, C, Germain, M, MacDonald, J, Braekkan, SK, Armasu, SM, Pankratz, N, Jackson, RD, Nielsen, JB, Giulianin, F, Puurunen, MK, Ibrahim, M, Heckbert, SR, Bammler, TK, McCauley, BM, Taylor, KD, Pankow, JS, Reiner, AP, Gabrielsen, ME, Deleuze, J-F, O'Donnell, CJ, Kim, J, McKnight, B, Kraft, P, Hansen, J-B, Rosendaal, FR, Heit, JA, Tang, W, Morange, P-E, Johnson, AD, Kabrhel, C, van Dijk, EJ, Koudstaal, PJ, Luijckx, G-J, Nederkoorn, PJ, van Oostenbrugge, RJ, Visser, MC, Wermer, MJH, Kappelle, LJ, Esko, T, Metspalu, A, Magi, R, Nelis, M, Levi, CR, Maguire, J, Jimenez-Conde, J, Sharma, P, Sudlow, CLM, Rannikmae, K, Schmidt, R, Slowik, A, Pera, J, Thijs, VNS, Lindgren, AG, Ilinca, A, Melander, O, Engstrom, G, Rexrode, KM, Rothwell, PM, Stanne, TM, Johnson, JA, Danesh, J, Butterworth, AS, Heitsch, L, Boncoraglio, GB, Kubo, M, Pezzini, A, Rolfs, A, Giese, A-K, Weir, D, Ross, OA, Lemmons, R, Soderholm, M, Cushman, M, Jood, K, McDonough, CW, Bell, S, Linkohr, B, Lee, T-H, Putaala, J, Lopez, OL, Carty, CL, Jian, X, Schminke, U, Cullell, N, Delgado, P, Ibanez, L, Krupinski, J, Lioutas, V, Matsuda, K, Montaner, J, Muino, E, Roquer, J, Sarnowski, C, Sattar, N, Sibolt, G, Teumer, A, Rutten-Jacobs, L, Kanai, M, Gretarsdottir, S, Rost, NS, Yusuf, S, Almgren, P, Ay, H, Bevan, S, Brown, RD, Carrera, C, Buring, JE, Chen, W-M, Cotlarciuc, I, de Bakker, PIW, DeStefano, AL, den Hoed, M, Duan, Q, Engelter, ST, Falcone, GJ, Gustafsson, S, Hassan, A, Holliday, EG, Howard, G, Hsu, F-C, Ingelsson, E, Harris, TB, Kissela, BM, Kleindorfer, DO, Langenberg, C, Leys, D, Lin, W-Y, Lorentzen, E, Magnusson, PK, McArdle, PF, Pulit, SL, Rice, K, Sakaue, S, Sapkota, BR, Tanislav, C, Thorleifsson, G, Thorsteinsdottir, U, Tzourio, C, van Duijn, CM, Walters, M, Wareham, NJ, Amin, N, Aparicio, HJ, Attia, J, Beiser, AS, Berr, C, Bustamante, M, Caso, V, Choi, SH, Chowhan, A, Dartigues, J-F, Delavaran, H, Dorr, M, Ford, I, Gurpreet, WS, Hamsten, A, Hozawa, A, Ingelsson, M, Iwasaki, M, Kaffashian, S, Kalra, L, Kjartansson, O, Kloss, M, Labovitz, DL, Laurie, CC, Lind, L, Lindgren, CM, Makoto, H, Minegishi, N, Morris, AP, Mueller-Nurasyid, M, Norrving, B, Ogishima, S, Parati, EA, Pedersen, NL, Perola, M, Jousilahti, P, Pileggi, S, Rabionet, R, Riba-Llena, I, Ribases, M, Romero, JR, Rudd, AG, Sarin, A-P, Sarju, R, Satoh, M, Sawada, N, Sigurdsson, A, Smith, A, Stine, OC, Stott, DJ, Strauch, K, Takai, T, Tanaka, H, Touze, E, Tsugane, S, Uitterlinden, AG, Valdimarsson, EM, van der Lee, SJ, Wakai, K, Williams, SR, Wolfe, CDA, Wong, Q, Yamaji, T, Sanghera, DK, Stefansson, K, Martinez-Majander, N, Sobue, K, Soriano-Tarraga, C, Volzke, H, Akpa, O, Sarfo, FS, Akpalu, A, Obiako, R, Wahab, K, Osaigbovo, G, Owolabi, L, Komolafe, M, Jenkins, C, Arulogun, O, Ogbole, G, Adeoye, AM, Akinyemi, J, Agunloye, A, Fakunle, AG, Uvere, E, Olalere, A, Adebajo, OJ, Chen, J, Clarke, R, Collins, R, Guo, Y, Wang, C, Lv, J, Peto, R, Chen, Y, Fairhurst-Hunter, Z, Hill, M, Pozarickij, A, Schmidt, D, Stevens, B, Turnbull, I, Yu, C, Nagai, A, Murakami, Y, Shiroma, EJ, Sigurdsson, S, Ghanbari, M, Boerwinkle, E, Fongang, B, Wang, R, Ikram, MK, Volker, U, de Laat, KF, van Norden, AGW, de Kort, PL, Vermeer, SE, Brouwers, PJAM, Gons, RAR, den Heijer, T, van Dijk, GW, van Rooij, FGW, Aamodt, AH, Skogholt, AH, Willer, CJ, Heuch, I, Hagen, K, Fritsche, LG, Pedersen, LM, Ellekjaer, H, Zhou, W, Martinsen, AE, Kristoffersen, ES, Thomas, LF, Kleinschnitz, C, Frantz, S, Ungethum, K, Gallego-Fabrega, C, Lledos, M, Llucia-Carol, L, Sobrino, T, Campos, F, Castillo, J, Freijo, M, Arenillas, JF, Obach, V, Alvarez-Sabin, J, Molina, CA, Ribo, M, Munoz-Narbona, L, Lopez-Cancio, E, Millan, M, Diaz-Navarro, R, Vives-Bauza, C, Serrano-Heras, G, Segura, T, Dhar, R, Delgado-Mederos, R, Prats-Sanchez, L, Camps-Renom, P, Blay, N, Sumoy, L, Marti-Fabregas, J, Schnohr, P, Jensen, GB, Benn, M, Afzal, S, Kamstrup, PR, van Setten, J, van der Laan, SW, Vonk, JMJ, Kim, B-J, Curtze, S, Tiainen, M, Kinnunen, J, Menon, V, Sung, YJ, Saillour-Glenisson, F, and Gravel, S
- Abstract
Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
- Published
- 2022
132. Stroke genetics informs drug discovery and risk prediction across ancestries
- Author
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Mishra, Aniket, Malik, Rainer, Hachiya, Tsuyoshi, Jurgenson, Tuuli, Namba, Shinichi, Posner, Daniel C, Kamanu, Frederick K, Koido, Masaru, Le Grand, Quentin, Shi, Mingyang, He, Yunye, Georgakis, Marios K, Caro, Ilana, Krebs, Kristi, Liaw, Yi-Ching, Vaura, Felix C, Lin, Kuang, Winsvold, Bendik Slagsvold, Srinivasasainagendra, Vinodh, Parodi, Livia, Bae, Hee-Joon, Chauhan, Ganesh, Chong, Michael R, Tomppo, Liisa, Akinyemi, Rufus, Roshchupkin, Gennady V, Habib, Naomi, Jee, Yon Ho, Thomassen, Jesper Qvist, Abedi, Vida, Carcel-Marquez, Jara, Nygaard, Marianne, Leonard, Hampton L, Yang, Chaojie, Yonova-Doing, Ekaterina, Knol, Maria J, Lewis, Adam J, Judy, Renae L, Ago, Tetsuro, Amouyel, Philippe, Armstrong, Nicole D, Bakker, Mark K, Bartz, Traci M, Bennett, David A, Bis, Joshua C, Bordes, Constance, Borte, Sigrid, Cain, Anael, Ridker, Paul M, Cho, Kelly, Chen, Zhengming, Cruchaga, Carlos, Cole, John W, de Jager, Phil L, de Cid, Rafael, Endres, Matthias, Ferreira, Leslie E, Geerlings, Mirjam I, Gasca, Natalie C, Gudnason, Vilmundur, Hata, Jun, He, Jing, Heath, Alicia K, Ho, Yuk-Lam, Havulinna, Aki S, Hopewell, Jemma C, Hyacinth, Hyacinth I, Inouye, Michael, Jacob, Mina A, Jeon, Christina E, Jern, Christina, Kamouchi, Masahiro, Keene, Keith L, Kitazono, Takanari, Kittner, Steven J, Konuma, Takahiro, Kumar, Amit, Lacaze, Paul, Launer, Lenore J, Lee, Keon-Joo, Lepik, Kaido, Li, Jiang, Li, Liming, Manichaikul, Ani, Markus, Hugh S, Marston, Nicholas A, Meitinger, Thomas, Mitchell, Braxton D, Montellano, Felipe A, Morisaki, Takayuki, Mosley, Thomas H, Nalls, Mike A, Nordestgaard, Borge G, O'Donnell, Martin J, Okada, Yukinori, Onland-Moret, N Charlotte, Ovbiagele, Bruce, Peters, Annette, Psaty, Bruce M, Rich, Stephen S, Rosand, Jonathan, Sabatine, Marc S, Sacco, Ralph L, Saleheen, Danish, Sandset, Else Charlotte, Salomaa, Veikko, Sargurupremraj, Muralidharan, Sasaki, Makoto, Satizabal, Claudia L, Schmidt, Carsten O, Shimizu, Atsushi, Smith, Nicholas L, Sloane, Kelly L, Sutoh, Yoichi, Sun, Yan V, Tanno, Kozo, Tiedt, Steffen, Tatlisumak, Turgut, Torres-Aguila, Nuria P, Tiwari, Hemant K, Tregouet, David-Alexandre, Trompet, Stella, Tuladhar, Anil Man, Tybjaerg-Hansen, Anne, van Vugt, Marion, Vibo, Riina, Verma, Shefali S, Wiggins, Kerri L, Wennberg, Patrik, Woo, Daniel, Wilson, Peter WF, Xu, Huichun, Yang, Qiong, Yoon, Kyungheon, Lee, Jin-Moo, Cheng, Yu-Ching, Meschia, James F, Chen, Wei Min, Sale, Michele M, Zonderman, Alan B, Evans, Michele K, Wilson, James G, Correa, Adolfo, Traylor, Matthew, Lewis, Cathryn M, Carty, Cara L, Reiner, Alexander, Haessler, Jeffrey, Langefeld, Carl D, Gottesman, Rebecca F, Yaffe, Kristine, Liu, Yong Mei, Kooperberg, Charles, Lange, Leslie A, Furie, Karen L, Arnett, Donna K, Benavente, Oscar R, Grewal, Raji P, Peddareddygari, Leema Reddy, Hveem, Kristian, Lindstrom, Sara, Wang, Lu, Smith, Erin N, Gordon, William, van Hylckama Vlieg, Astrid, de Andrade, Mariza, Brody, Jennifer A, Pattee, Jack W, Brumpton, Ben M, Suchon, Pierre, Chen, Ming-Huei, Frazer, Kelly A, Turman, Constance, Germain, Marine, MacDonald, James, Braekkan, Sigrid K, Armasu, Sebastian M, Pankratz, Nathan, Jackson, Rebecca D, Nielsen, Jonas B, Giulianini, Franco, Puurunen, Marja K, Ibrahim, Manal, Heckbert, Susan R, Bammler, Theo K, McCauley, Bryan M, Taylor, Kent D, Pankow, James S, Reiner, Alexander P, Gabrielsen, Maiken E, Deleuze, Jean-Francois, O'Donnell, Chris J, Kim, Jihye, McKnight, Barbara, Kraft, Peter, Hansen, John-Bjarne, Rosendaal, Frits R, Heit, John A, Tang, Weihong, Morange, Pierre-Emmanuel, Johnson, Andrew D, Kabrhel, Christopher, van Dijk, Ewoud J, Koudstaal, Peter J, Luijckx, Gert-Jan, Nederkoorn, Paul J, van Oostenbrugge, Robert J, Visser, Marieke C, Wermer, Marieke JH, Kappelle, L Jaap, Esko, Tonu, Metspalu, Andres, Magi, Reedik, Nelis, Mari, Irvin, Marguerite R, de Leeuw, Frank-Erik, Levi, Christopher R, Maguire, Jane, Jimenez-Conde, Jordi, Sharma, Pankaj, Sudlow, Cathie LM, Rannikmae, Kristiina, Schmidt, Reinhold, Slowik, Agnieszka, Pera, Joanna, Thijs, Vincent NS, Lindgren, Arne G, Ilinca, Andreea, Melander, Olle, Engstrom, Gunnar, Rexrode, Kathryn M, Rothwell, Peter M, Stanne, Tara M, Johnson, Julie A, Danesh, John, Butterworth, Adam S, Heitsch, Laura, Boncoraglio, Giorgio B, Kubo, Michiaki, Pezzini, Alessandro, Rolfs, Arndt, Giese, Anne-Katrin, Weir, David, Ross, Owen A, Lemmons, Robin, Soderholm, Martin, Cushman, Mary, Jood, Katarina, McDonough, Caitrin W, Bell, Steven, Linkohr, Birgit, Lee, Tsong-Hai, Putaala, Jukka, Anderson, Christopher D, Lopez, Oscar L, Jian, Xueqiu, Schminke, Ulf, Cullell, Natalia, Delgado, Pilar, Ibanez, Laura, Krupinski, Jerzy, Lioutas, Vasileios, Matsuda, Koichi, Montaner, Joan, Muino, Elena, Roquer, Jaume, Sarnowski, Chloe, Sattar, Naveed, Sibolt, Gerli, Teumer, Alexander, Rutten-Jacobs, Loes, Kanai, Masahiro, Gretarsdottir, Solveig, Rost, Natalia S, Yusuf, Salim, Almgren, Peter, Ay, Hakan, Bevan, Steve, Brown, Robert D, Carrera, Caty, Buring, Julie E, Chen, Wei-Min, Cotlarciuc, Ioana, de Bakker, Paul IW, DeStefano, Anita L, den Hoed, Marcel, Duan, Qing, Engelter, Stefan T, Falcone, Guido J, Gustafsson, Stefan, Hassan, Ahamad, Holliday, Elizabeth G, Howard, George, Hsu, Fang-Chi, Ingelsson, Erik, Harris, Tamara B, Kissela, Brett M, Kleindorfer, Dawn O, Langenberg, Claudia, Lemmens, Robin, Leys, Didier, Lin, Wei-Yu, Lorentzen, Erik, Magnusson, Patrik K, McArdle, Patrick F, Pulit, Sara L, Rice, Kenneth, Sakaue, Saori, Sapkota, Bishwa R, Tanislav, Christian, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tzourio, Christophe, van Duijn, Cornelia M, Walters, Matthew, Wareham, Nicholas J, Amin, Najaf, Aparicio, Hugo J, Attia, John, Beiser, Alexa S, Berr, Claudine, Bustamante, Mariana, Caso, Valeria, Choi, Seung Hoan, Chowhan, Ayesha, Dartigues, Jean-Francois, Delavaran, Hossein, Dorr, Marcus, Ford, Ian, Gurpreet, Wander S, Hamsten, Anders, Hozawa, Atsushi, Ingelsson, Martin, Iwasaki, Motoki, Kaffashian, Sara, Kalra, Lalit, Kjartansson, Olafur, Kloss, Manja, Labovitz, Daniel L, Laurie, Cathy C, Li, Linxin, Lind, Lars, Lindgren, Cecilia M, Makoto, Hirata, Minegishi, Naoko, Morris, Andrew P, Muller-Nurasyid, Martina, Norrving, Bo, Ogishima, Soichi, Parati, Eugenio A, Pedersen, Nancy L, Perola, Markus, Jousilahti, Pekka, Pileggi, Silvana, Rabionet, Raquel, Riba-Llena, Iolanda, Ribases, Marta, Romero, Jose R, Rudd, Anthony G, Sarin, Antti-Pekka, Sarju, Ralhan, Satoh, Mamoru, Sawada, Norie, Sigurdsson, Asgeir, Smith, Albert, Stine, O Colin, Stott, David J, Strauch, Konstantin, Takai, Takako, Tanaka, Hideo, Touze, Emmanuel, Tsugane, Shoichiro, Uitterlinden, Andre G, Valdimarsson, Einar M, van der Lee, Sven J, Wakai, Kenji, Williams, Stephen R, Wolfe, Charles DA, Wong, Quenna, Yamaji, Taiki, Sanghera, Dharambir K, Stefansson, Kari, Martinez-Majander, Nicolas, Sobue, Kenji, Soriano-Tarraga, Carolina, Volzke, Henry, Akpa, Onoja, Sarfo, Fred S, Akpalu, Albert, Obiako, Reginald, Wahab, Kolawole, Osaigbovo, Godwin, Owolabi, Lukman, Komolafe, Morenikeji, Jenkins, Carolyn, Arulogun, Oyedunni, Ogbole, Godwin, Adeoye, Abiodun M, Akinyemi, Joshua, Agunloye, Atinuke, Fakunle, Adekunle G, Uvere, Ezinne, Olalere, Abimbola, Adebajo, Olayinka J, Chen, Junshi, Clarke, Robert, Collins, Rory, Guo, Yu, Wang, Chen, Lv, Jun, Peto, Richard, Chen, Yiping, Fairhurst-Hunter, Zammy, Hill, Michael, Pozarickij, Alfred, Schmidt, Dan, Stevens, Becky, Turnbull, Iain, Yu, Canqing, Nagai, Akiko, Murakami, Yoishinori, Shiroma, Eric J, Sigurdsson, Sigurdur, Ghanbari, Mohsen, Boerwinkle, Eric, Fongang, Bernard, Wang, Ruiqi, Ikram, Mohammad K, Volker, Uwe, de Laat, Karlijn F, van Norden, Anouk GW, de Kort, Paul L, Vermeer, Sarah E, Brouwers, Paul JAM, Gons, Rob AR, den Heijer, Tom, van Dijk, Gert W, van Rooij, Frank GW, Aamodt, Anne H, Skogholt, Anne H, Willer, Cristen J, Heuch, Ingrid, Hagen, Knut, Fritsche, Lars G, Pedersen, Linda M, Ellekjaer, Hanne, Zhou, Wei, Martinsen, Amy E, Kristoffersen, Espen S, Thomas, Laurent F, Kleinschnitz, Christoph, Frantz, Stefan, Ungethum, Kathrin, Gallego-Fabrega, Cristina, Lledos, Miquel, Llucia-Carol, Laia, Sobrino, Tomas, Campos, Francisco, Castillo, Jose, Freijo, Marimar, Arenillas, Juan Francisco, Obach, Victor, Alvarez-Sabin, Jose, Molina, Carlos A, Ribo, Marc, Munoz-Narbona, Lucia, Lopez-Cancio, Elena, Millan, Monica, Diaz-Navarro, Rosa, Vives-Bauza, Cristofol, Serrano-Heras, Gemma, Segura, Tomas, Dhar, Rajat, Delgado-Mederos, Raquel, Prats-Sanchez, Luis, Camps-Renom, Pol, Blay, Natalia, Sumoy, Lauro, Marti-Fabregas, Joan, Schnohr, Peter, Jensen, Gorm B, Benn, Marianne, Afzal, Shoaib, Kamstrup, Pia R, van Setten, Jessica, van der Laan, Sander W, Vonk, Jet MJ, Kim, Bong-Jo, Curtze, Sami, Tiainen, Marjaana, Kinnunen, Janne, Menon, Vilas, Sung, Yun Ju, Yang, Chengran, Saillour-Glenisson, Florence, Gravel, Simon, Millwood, Iona Y, Gieger, Christian, Ninomiya, Toshiharu, Grabe, Hans J, Jukema, J Wouter, Rissanen, Ina L, Strbian, Daniel, Kim, Young Jin, Chen, Pei-Hsin, Mayerhofer, Ernst, Howson, Joanna MM, Adams, Hieab, Wassertheil-Smoller, Sylvia, Christensen, Kaare, Ikram, Mohammad A, Rundek, Tatjana, Worrall, Bradford B, Lathrop, G Mark, Riaz, Moeen, Simonsick, Eleanor M, Korv, Janika, Franca, Paulo HC, Zand, Ramin, Prasad, Kameshwar, Frikke-Schmidt, Ruth, Liman, Thomas, Haeusler, Karl Georg, Ruigrok, Ynte M, Heuschmann, Peter Ulrich, Longstreth, WT, Jung, Keum Ji, Bastarache, Lisa, Pare, Guillaume, Damrauer, Scott M, Chasman, Daniel I, Rotter, Jerome I, Zwart, John-Anker, Niiranen, Teemu J, Fornage, Myriam, Liaw, Yung-Po, Seshadri, Sudha, Fernandez-Cadenas, Israel, Walters, Robin G, Ruff, Christian T, Owolabi, Mayowa O, Huffman, Jennifer E, Milani, Lili, Kamatani, Yoichiro, Dichgans, Martin, Debette, Stephanie, Mishra, Aniket, Malik, Rainer, Hachiya, Tsuyoshi, Jurgenson, Tuuli, Namba, Shinichi, Posner, Daniel C, Kamanu, Frederick K, Koido, Masaru, Le Grand, Quentin, Shi, Mingyang, He, Yunye, Georgakis, Marios K, Caro, Ilana, Krebs, Kristi, Liaw, Yi-Ching, Vaura, Felix C, Lin, Kuang, Winsvold, Bendik Slagsvold, Srinivasasainagendra, Vinodh, Parodi, Livia, Bae, Hee-Joon, Chauhan, Ganesh, Chong, Michael R, Tomppo, Liisa, Akinyemi, Rufus, Roshchupkin, Gennady V, Habib, Naomi, Jee, Yon Ho, Thomassen, Jesper Qvist, Abedi, Vida, Carcel-Marquez, Jara, Nygaard, Marianne, Leonard, Hampton L, Yang, Chaojie, Yonova-Doing, Ekaterina, Knol, Maria J, Lewis, Adam J, Judy, Renae L, Ago, Tetsuro, Amouyel, Philippe, Armstrong, Nicole D, Bakker, Mark K, Bartz, Traci M, Bennett, David A, Bis, Joshua C, Bordes, Constance, Borte, Sigrid, Cain, Anael, Ridker, Paul M, Cho, Kelly, Chen, Zhengming, Cruchaga, Carlos, Cole, John W, de Jager, Phil L, de Cid, Rafael, Endres, Matthias, Ferreira, Leslie E, Geerlings, Mirjam I, Gasca, Natalie C, Gudnason, Vilmundur, Hata, Jun, He, Jing, Heath, Alicia K, Ho, Yuk-Lam, Havulinna, Aki S, Hopewell, Jemma C, Hyacinth, Hyacinth I, Inouye, Michael, Jacob, Mina A, Jeon, Christina E, Jern, Christina, Kamouchi, Masahiro, Keene, Keith L, Kitazono, Takanari, Kittner, Steven J, Konuma, Takahiro, Kumar, Amit, Lacaze, Paul, Launer, Lenore J, Lee, Keon-Joo, Lepik, Kaido, Li, Jiang, Li, Liming, Manichaikul, Ani, Markus, Hugh S, Marston, Nicholas A, Meitinger, Thomas, Mitchell, Braxton D, Montellano, Felipe A, Morisaki, Takayuki, Mosley, Thomas H, Nalls, Mike A, Nordestgaard, Borge G, O'Donnell, Martin J, Okada, Yukinori, Onland-Moret, N Charlotte, Ovbiagele, Bruce, Peters, Annette, Psaty, Bruce M, Rich, Stephen S, Rosand, Jonathan, Sabatine, Marc S, Sacco, Ralph L, Saleheen, Danish, Sandset, Else Charlotte, Salomaa, Veikko, Sargurupremraj, Muralidharan, Sasaki, Makoto, Satizabal, Claudia L, Schmidt, Carsten O, Shimizu, Atsushi, Smith, Nicholas L, Sloane, Kelly L, Sutoh, Yoichi, Sun, Yan V, Tanno, Kozo, Tiedt, Steffen, Tatlisumak, Turgut, Torres-Aguila, Nuria P, Tiwari, Hemant K, Tregouet, David-Alexandre, Trompet, Stella, Tuladhar, Anil Man, Tybjaerg-Hansen, Anne, van Vugt, Marion, Vibo, Riina, Verma, Shefali S, Wiggins, Kerri L, Wennberg, Patrik, Woo, Daniel, Wilson, Peter WF, Xu, Huichun, Yang, Qiong, Yoon, Kyungheon, Lee, Jin-Moo, Cheng, Yu-Ching, Meschia, James F, Chen, Wei Min, Sale, Michele M, Zonderman, Alan B, Evans, Michele K, Wilson, James G, Correa, Adolfo, Traylor, Matthew, Lewis, Cathryn M, Carty, Cara L, Reiner, Alexander, Haessler, Jeffrey, Langefeld, Carl D, Gottesman, Rebecca F, Yaffe, Kristine, Liu, Yong Mei, Kooperberg, Charles, Lange, Leslie A, Furie, Karen L, Arnett, Donna K, Benavente, Oscar R, Grewal, Raji P, Peddareddygari, Leema Reddy, Hveem, Kristian, Lindstrom, Sara, Wang, Lu, Smith, Erin N, Gordon, William, van Hylckama Vlieg, Astrid, de Andrade, Mariza, Brody, Jennifer A, Pattee, Jack W, Brumpton, Ben M, Suchon, Pierre, Chen, Ming-Huei, Frazer, Kelly A, Turman, Constance, Germain, Marine, MacDonald, James, Braekkan, Sigrid K, Armasu, Sebastian M, Pankratz, Nathan, Jackson, Rebecca D, Nielsen, Jonas B, Giulianini, Franco, Puurunen, Marja K, Ibrahim, Manal, Heckbert, Susan R, Bammler, Theo K, McCauley, Bryan M, Taylor, Kent D, Pankow, James S, Reiner, Alexander P, Gabrielsen, Maiken E, Deleuze, Jean-Francois, O'Donnell, Chris J, Kim, Jihye, McKnight, Barbara, Kraft, Peter, Hansen, John-Bjarne, Rosendaal, Frits R, Heit, John A, Tang, Weihong, Morange, Pierre-Emmanuel, Johnson, Andrew D, Kabrhel, Christopher, van Dijk, Ewoud J, Koudstaal, Peter J, Luijckx, Gert-Jan, Nederkoorn, Paul J, van Oostenbrugge, Robert J, Visser, Marieke C, Wermer, Marieke JH, Kappelle, L Jaap, Esko, Tonu, Metspalu, Andres, Magi, Reedik, Nelis, Mari, Irvin, Marguerite R, de Leeuw, Frank-Erik, Levi, Christopher R, Maguire, Jane, Jimenez-Conde, Jordi, Sharma, Pankaj, Sudlow, Cathie LM, Rannikmae, Kristiina, Schmidt, Reinhold, Slowik, Agnieszka, Pera, Joanna, Thijs, Vincent NS, Lindgren, Arne G, Ilinca, Andreea, Melander, Olle, Engstrom, Gunnar, Rexrode, Kathryn M, Rothwell, Peter M, Stanne, Tara M, Johnson, Julie A, Danesh, John, Butterworth, Adam S, Heitsch, Laura, Boncoraglio, Giorgio B, Kubo, Michiaki, Pezzini, Alessandro, Rolfs, Arndt, Giese, Anne-Katrin, Weir, David, Ross, Owen A, Lemmons, Robin, Soderholm, Martin, Cushman, Mary, Jood, Katarina, McDonough, Caitrin W, Bell, Steven, Linkohr, Birgit, Lee, Tsong-Hai, Putaala, Jukka, Anderson, Christopher D, Lopez, Oscar L, Jian, Xueqiu, Schminke, Ulf, Cullell, Natalia, Delgado, Pilar, Ibanez, Laura, Krupinski, Jerzy, Lioutas, Vasileios, Matsuda, Koichi, Montaner, Joan, Muino, Elena, Roquer, Jaume, Sarnowski, Chloe, Sattar, Naveed, Sibolt, Gerli, Teumer, Alexander, Rutten-Jacobs, Loes, Kanai, Masahiro, Gretarsdottir, Solveig, Rost, Natalia S, Yusuf, Salim, Almgren, Peter, Ay, Hakan, Bevan, Steve, Brown, Robert D, Carrera, Caty, Buring, Julie E, Chen, Wei-Min, Cotlarciuc, Ioana, de Bakker, Paul IW, DeStefano, Anita L, den Hoed, Marcel, Duan, Qing, Engelter, Stefan T, Falcone, Guido J, Gustafsson, Stefan, Hassan, Ahamad, Holliday, Elizabeth G, Howard, George, Hsu, Fang-Chi, Ingelsson, Erik, Harris, Tamara B, Kissela, Brett M, Kleindorfer, Dawn O, Langenberg, Claudia, Lemmens, Robin, Leys, Didier, Lin, Wei-Yu, Lorentzen, Erik, Magnusson, Patrik K, McArdle, Patrick F, Pulit, Sara L, Rice, Kenneth, Sakaue, Saori, Sapkota, Bishwa R, Tanislav, Christian, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tzourio, Christophe, van Duijn, Cornelia M, Walters, Matthew, Wareham, Nicholas J, Amin, Najaf, Aparicio, Hugo J, Attia, John, Beiser, Alexa S, Berr, Claudine, Bustamante, Mariana, Caso, Valeria, Choi, Seung Hoan, Chowhan, Ayesha, Dartigues, Jean-Francois, Delavaran, Hossein, Dorr, Marcus, Ford, Ian, Gurpreet, Wander S, Hamsten, Anders, Hozawa, Atsushi, Ingelsson, Martin, Iwasaki, Motoki, Kaffashian, Sara, Kalra, Lalit, Kjartansson, Olafur, Kloss, Manja, Labovitz, Daniel L, Laurie, Cathy C, Li, Linxin, Lind, Lars, Lindgren, Cecilia M, Makoto, Hirata, Minegishi, Naoko, Morris, Andrew P, Muller-Nurasyid, Martina, Norrving, Bo, Ogishima, Soichi, Parati, Eugenio A, Pedersen, Nancy L, Perola, Markus, Jousilahti, Pekka, Pileggi, Silvana, Rabionet, Raquel, Riba-Llena, Iolanda, Ribases, Marta, Romero, Jose R, Rudd, Anthony G, Sarin, Antti-Pekka, Sarju, Ralhan, Satoh, Mamoru, Sawada, Norie, Sigurdsson, Asgeir, Smith, Albert, Stine, O Colin, Stott, David J, Strauch, Konstantin, Takai, Takako, Tanaka, Hideo, Touze, Emmanuel, Tsugane, Shoichiro, Uitterlinden, Andre G, Valdimarsson, Einar M, van der Lee, Sven J, Wakai, Kenji, Williams, Stephen R, Wolfe, Charles DA, Wong, Quenna, Yamaji, Taiki, Sanghera, Dharambir K, Stefansson, Kari, Martinez-Majander, Nicolas, Sobue, Kenji, Soriano-Tarraga, Carolina, Volzke, Henry, Akpa, Onoja, Sarfo, Fred S, Akpalu, Albert, Obiako, Reginald, Wahab, Kolawole, Osaigbovo, Godwin, Owolabi, Lukman, Komolafe, Morenikeji, Jenkins, Carolyn, Arulogun, Oyedunni, Ogbole, Godwin, Adeoye, Abiodun M, Akinyemi, Joshua, Agunloye, Atinuke, Fakunle, Adekunle G, Uvere, Ezinne, Olalere, Abimbola, Adebajo, Olayinka J, Chen, Junshi, Clarke, Robert, Collins, Rory, Guo, Yu, Wang, Chen, Lv, Jun, Peto, Richard, Chen, Yiping, Fairhurst-Hunter, Zammy, Hill, Michael, Pozarickij, Alfred, Schmidt, Dan, Stevens, Becky, Turnbull, Iain, Yu, Canqing, Nagai, Akiko, Murakami, Yoishinori, Shiroma, Eric J, Sigurdsson, Sigurdur, Ghanbari, Mohsen, Boerwinkle, Eric, Fongang, Bernard, Wang, Ruiqi, Ikram, Mohammad K, Volker, Uwe, de Laat, Karlijn F, van Norden, Anouk GW, de Kort, Paul L, Vermeer, Sarah E, Brouwers, Paul JAM, Gons, Rob AR, den Heijer, Tom, van Dijk, Gert W, van Rooij, Frank GW, Aamodt, Anne H, Skogholt, Anne H, Willer, Cristen J, Heuch, Ingrid, Hagen, Knut, Fritsche, Lars G, Pedersen, Linda M, Ellekjaer, Hanne, Zhou, Wei, Martinsen, Amy E, Kristoffersen, Espen S, Thomas, Laurent F, Kleinschnitz, Christoph, Frantz, Stefan, Ungethum, Kathrin, Gallego-Fabrega, Cristina, Lledos, Miquel, Llucia-Carol, Laia, Sobrino, Tomas, Campos, Francisco, Castillo, Jose, Freijo, Marimar, Arenillas, Juan Francisco, Obach, Victor, Alvarez-Sabin, Jose, Molina, Carlos A, Ribo, Marc, Munoz-Narbona, Lucia, Lopez-Cancio, Elena, Millan, Monica, Diaz-Navarro, Rosa, Vives-Bauza, Cristofol, Serrano-Heras, Gemma, Segura, Tomas, Dhar, Rajat, Delgado-Mederos, Raquel, Prats-Sanchez, Luis, Camps-Renom, Pol, Blay, Natalia, Sumoy, Lauro, Marti-Fabregas, Joan, Schnohr, Peter, Jensen, Gorm B, Benn, Marianne, Afzal, Shoaib, Kamstrup, Pia R, van Setten, Jessica, van der Laan, Sander W, Vonk, Jet MJ, Kim, Bong-Jo, Curtze, Sami, Tiainen, Marjaana, Kinnunen, Janne, Menon, Vilas, Sung, Yun Ju, Yang, Chengran, Saillour-Glenisson, Florence, Gravel, Simon, Millwood, Iona Y, Gieger, Christian, Ninomiya, Toshiharu, Grabe, Hans J, Jukema, J Wouter, Rissanen, Ina L, Strbian, Daniel, Kim, Young Jin, Chen, Pei-Hsin, Mayerhofer, Ernst, Howson, Joanna MM, Adams, Hieab, Wassertheil-Smoller, Sylvia, Christensen, Kaare, Ikram, Mohammad A, Rundek, Tatjana, Worrall, Bradford B, Lathrop, G Mark, Riaz, Moeen, Simonsick, Eleanor M, Korv, Janika, Franca, Paulo HC, Zand, Ramin, Prasad, Kameshwar, Frikke-Schmidt, Ruth, Liman, Thomas, Haeusler, Karl Georg, Ruigrok, Ynte M, Heuschmann, Peter Ulrich, Longstreth, WT, Jung, Keum Ji, Bastarache, Lisa, Pare, Guillaume, Damrauer, Scott M, Chasman, Daniel I, Rotter, Jerome I, Zwart, John-Anker, Niiranen, Teemu J, Fornage, Myriam, Liaw, Yung-Po, Seshadri, Sudha, Fernandez-Cadenas, Israel, Walters, Robin G, Ruff, Christian T, Owolabi, Mayowa O, Huffman, Jennifer E, Milani, Lili, Kamatani, Yoichiro, Dichgans, Martin, and Debette, Stephanie
- Abstract
Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
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- 2022
133. Allele-specific regulation of MTTP expression influences the risk of ischemic heart disease[S]
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Anna Aminoff, Helena Ledmyr, Petra Thulin, Kerstin Lundell, Leyla Nunez, Elisabeth Strandhagen, Charlotte Murphy, Ulf Lidberg, Jukka Westerbacka, Anders Franco-Cereceda, Jan Liska, Lars Bo Nielsen, Mats Gåfvels, Maria Nastase Mannila, Anders Hamsten, Hannele Yki-Järvinen, Dag Thelle, Per Eriksson, Jan Borén, and Ewa Ehrenborg
- Subjects
promoter activity ,lipotoxicity ,lipid accumulation ,myocardium ,Biochemistry ,QD415-436 - Abstract
Promoter polymorphisms in microsomal triglyceride transfer protein (MTTP) have been associated with decreased plasma lipids but an increased risk for ischemic heart disease (IHD), indicating that MTTP influences the susceptibility for IHD independent of plasma lipids. The objective of this study was to characterize the functional promoter polymorphism in MTTP predisposing to IHD and its underlying mechanism. Use of pyrosequencing technology revealed that presence of the minor alleles of the promoter polymorphisms -493G>T and -164T>C result in lower transcription of MTTP in vivo in the heart, liver, and macrophages. In vitro experiments indicated that the minor -164C allele mediates the lower gene expression and that C/EBP binds to the polymorphic region in an allele-specific manner. Furthermore, homozygous carriers of the -164C were found to have increased risk for IHD as shown in a case-control study including a total of 544 IHD patients and 544 healthy control subjects. We concluded that carriers of the minor -164C allele have lower expression of MTTP in the heart, mediated at least partly by the transcription factor CCAAT/enhancer binding protein, and that reduced concentration of MTTP in the myocardium may contribute to IHD upon ischemic damage.
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- 2010
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134. Blood Pressure Loci Identified with a Gene-Centric Array
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Johnson, Toby, Gaunt, Tom R., Newhouse, Stephen J., Padmanabhan, Sandosh, Tomaszewski, Maciej, Kumari, Meena, Morris, Richard W., Tzoulaki, Ioanna, O'Brien, Eoin T., Poulter, Neil R., Sever, Peter, Shields, Denis C., Thom, Simon, Wannamethee, Sasiwarang G., Whincup, Peter H., Brown, Morris J., Connell, John M., Dobson, Richard J., Howard, Philip J., Mein, Charles A., Onipinla, Abiodun, Shaw-Hawkins, Sue, Zhang, Yun, Smith, George Davey, Day, Ian N.M., Lawlor, Debbie A., Goodall, Alison H., Fowkes, F. Gerald, Abecasis, Gonçalo R., Elliott, Paul, Gateva, Vesela, Braund, Peter S., Burton, Paul R., Nelson, Christopher P., Tobin, Martin D., van der Harst, Pim, Glorioso, Nicola, Neuvrith, Hani, Salvi, Erika, Staessen, Jan A., Stucchi, Andrea, Devos, Nabila, Jeunemaitre, Xavier, Plouin, Pierre-François, Tichet, Jean, Juhanson, Peeter, Org, Elin, Putku, Margus, Sõber, Siim, Veldre, Gudrun, Viigimaa, Margus, Levinsson, Anna, Rosengren, Annika, Thelle, Dag S., Hastie, Claire E., Hedner, Thomas, Lee, Wai K., Melander, Olle, Wahlstrand, Björn, Hardy, Rebecca, Wong, Andrew, Cooper, Jackie A., Palmen, Jutta, Chen, Li, Stewart, Alexandre F.R., Wells, George A., Westra, Harm-Jan, Wolfs, Marcel G.M., Clarke, Robert, Franzosi, Maria Grazia, Goel, Anuj, Hamsten, Anders, Lathrop, Mark, Peden, John F., Seedorf, Udo, Watkins, Hugh, Ouwehand, Willem H., Sambrook, Jennifer, Stephens, Jonathan, Casas, Juan-Pablo, Drenos, Fotios, Holmes, Michael V., Kivimaki, Mika, Shah, Sonia, Shah, Tina, Talmud, Philippa J., Whittaker, John, Wallace, Chris, Delles, Christian, Laan, Maris, Kuh, Diana, Humphries, Steve E., Nyberg, Fredrik, Cusi, Daniele, Roberts, Robert, Newton-Cheh, Christopher, Franke, Lude, Stanton, Alice V., Dominiczak, Anna F., Farrall, Martin, Hingorani, Aroon D., Samani, Nilesh J., Caulfield, Mark J., and Munroe, Patricia B.
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- 2011
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135. Meta-analysis of Dense Genecentric Association Studies Reveals Common and Uncommon Variants Associated with Height
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Lanktree, Matthew B., Guo, Yiran, Murtaza, Muhammed, Glessner, Joseph T., Bailey, Swneke D., Onland-Moret, N. Charlotte, Lettre, Guillaume, Ongen, Halit, Rajagopalan, Ramakrishnan, Johnson, Toby, Shen, Haiqing, Nelson, Christopher P., Klopp, Norman, Baumert, Jens, Padmanabhan, Sandosh, Pankratz, Nathan, Pankow, James S., Shah, Sonia, Taylor, Kira, Barnard, John, Peters, Bas J., M. Maloney, Cliona, Lobmeyer, Maximilian T., Stanton, Alice, Zafarmand, M. Hadi, Romaine, Simon P.R., Mehta, Amar, van Iperen, Erik P.A., Gong, Yan, Price, Tom S., Smith, Erin N., Kim, Cecilia E., Li, Yun R., Asselbergs, Folkert W., Atwood, Larry D., Bailey, Kristian M., Bhatt, Deepak, Bauer, Florianne, Behr, Elijah R., Bhangale, Tushar, Boer, Jolanda M.A., Boehm, Bernhard O., Bradfield, Jonathan P., Brown, Morris, Braund, Peter S., Burton, Paul R., Carty, Cara, Chandrupatla, Hareesh R., Chen, Wei, Connell, John, Dalgeorgou, Chrysoula, Boer, Anthonius de, Drenos, Fotios, Elbers, Clara C., Fang, James C., Fox, Caroline S., Frackelton, Edward C., Fuchs, Barry, Furlong, Clement E., Gibson, Quince, Gieger, Christian, Goel, Anuj, Grobbee, Diederik E., Hastie, Claire, Howard, Philip J., Huang, Guan-Hua, Johnson, W. Craig, Li, Qing, Kleber, Marcus E., Klein, Barbara E.K., Klein, Ronald, Kooperberg, Charles, Ky, Bonnie, LaCroix, Andrea, Lanken, Paul, Lathrop, Mark, Li, Mingyao, Marshall, Vanessa, Melander, Olle, Mentch, Frank D., J. Meyer, Nuala, Monda, Keri L., Montpetit, Alexandre, Murugesan, Gurunathan, Nakayama, Karen, Nondahl, Dave, Onipinla, Abiodun, Rafelt, Suzanne, Newhouse, Stephen J., Otieno, F. George, Patel, Sanjey R., Putt, Mary E., Rodriguez, Santiago, Safa, Radwan N., Sawyer, Douglas B., Schreiner, Pamela J., Simpson, Claire, Sivapalaratnam, Suthesh, Srinivasan, Sathanur R., Suver, Christine, Swergold, Gary, Sweitzer, Nancy K., Thomas, Kelly A., Thorand, Barbara, Timpson, Nicholas J., Tischfield, Sam, Tobin, Martin, Tomaszweski, Maciej, Verschuren, W.M. Monique, Wallace, Chris, Winkelmann, Bernhard, Zhang, Haitao, Zheng, Dongling, Zhang, Li, Zmuda, Joseph M., Clarke, Robert, Balmforth, Anthony J., Danesh, John, Day, Ian N., Schork, Nicholas J., de Bakker, Paul I.W., Delles, Christian, Duggan, David, Hingorani, Aroon D., Hirschhorn, Joel N., Hofker, Marten H., Humphries, Steve E., Kivimaki, Mika, Lawlor, Debbie A., Kottke-Marchant, Kandice, Mega, Jessica L., Mitchell, Braxton D., Morrow, David A., Palmen, Jutta, Redline, Susan, Shields, Denis C., Shuldiner, Alan R., Sleiman, Patrick M., Smith, George Davey, Farrall, Martin, Jamshidi, Yalda, Christiani, David C., Casas, Juan P., Hall, Alistair S., Doevendans, Pieter A., D. Christie, Jason, Berenson, Gerald S., Murray, Sarah S., Illig, Thomas, Dorn, Gerald W., II, Cappola, Thomas P., Boerwinkle, Eric, Sever, Peter, Rader, Daniel J., Reilly, Muredach P., Caulfield, Mark, Talmud, Philippa J., Topol, Eric, Engert, James C., Wang, Kai, Dominiczak, Anna, Hamsten, Anders, Curtis, Sean P., Silverstein, Roy L., Lange, Leslie A., Sabatine, Marc S., Trip, Mieke, Saleheen, Danish, Peden, John F., Cruickshanks, Karen J., März, Winfried, O'Connell, Jeffrey R., Klungel, Olaf H., Wijmenga, Cisca, Maitland-van der Zee, Anke Hilse, Schadt, Eric E., Johnson, Julie A., Jarvik, Gail P., Papanicolaou, George J., Grant, Struan F.A., Munroe, Patricia B., North, Kari E., Samani, Nilesh J., Koenig, Wolfgang, Gaunt, Tom R., Anand, Sonia S., van der Schouw, Yvonne T., Soranzo, Nicole, FitzGerald, Garret A., Reiner, Alex, Hegele, Robert A., Hakonarson, Hakon, and Keating, Brendan J.
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- 2011
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136. The prevalence of peripheral neuropathy in a population-based study of patients with type 2 diabetes in Sweden
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Kärvestedt, Lars, Mårtensson, Eva, Grill, Valdemar, Elofsson, Stig, von Wendt, Gunvor, Hamsten, Anders, and Brismar, Kerstin
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- 2011
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137. Human C-Reactive Protein Slows Atherosclerosis Development in a Mouse Model with Human-Like Hypercholesterolemia
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Kovacs, Alexander, Tornvall, Per, Nilsson, Roland, Tegnér, Jesper, Hamsten, Anders, and Björkegren, Johan
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- 2007
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138. Auxilin is a novel susceptibility gene for congenital heart block which directly impacts fetal heart function
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Meisgen, Sabrina, primary, Hedlund, Malin, additional, Ambrosi, Aurelie, additional, Folkersen, Lasse, additional, Ottosson, Vijole, additional, Forsberg, David, additional, Thorlacius, Gudny Ella, additional, Biavati, Luca, additional, Strandberg, Linn, additional, Mofors, Johannes, additional, Ramskold, Daniel, additional, Ruhrmann, Sabrina, additional, Meneghel, Lauro, additional, Nyberg, William, additional, Espinosa, Alexander, additional, Hamilton, Robert Murray, additional, Franco-Cereceda, Anders, additional, Hamsten, Anders, additional, Olsson, Tomas, additional, Greene, Lois, additional, Eriksson, Per, additional, Gemzell-Danielsson, Kristina, additional, Salomonsson, Stina, additional, Kuchroo, Vijay K, additional, Herlenius, Eric, additional, Kockum, Ingrid, additional, Sonesson, Sven-Erik, additional, and Wahren-Herlenius, Marie, additional
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- 2022
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139. Genome-wide analysis in over 1 million individuals reveals over 2,000 independent genetic signals for blood pressure
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Helen Warren, Todd Edwards, Ahmad Vaez, Jacob Keaton, Zoha Kamali, Tian Xie, Alireza Ani, Evangelos Evangelou, Jacklyn Hellwege, Loïc Yengo, William Young, Matthew Traylor, Ayush Giri, Peter Visscher, Daniel Chasman, Andrew Morris, Mark Caulfield, Shih-Jen Hwang, Jaspal Kooner, David Conen, John Attia, Alanna Morrison, Ruth Loos, Kati Kristiansson, Reinhold Schmidt, Andrew Hicks, Peter Pramstaller, Christopher Nelson, Nilesh Samani, Lorenz Risch, Ulf Gyllensten, Olle Melander, Harriëtte Riese, James Wilson, Harry Campbell, Bruce Psaty, Yingchang Lu, Jerome Rotter, Xiuqing Guo, Kenneth Rice, Peter Vollenweider, Johan Sundstrom, Claudia Langenberg, Martin Tobin, Vilmantas Giedraitis, Jian'an Luan, Jaakko Tuomilehto, Zoltan Kutalik, Samuli Ripatti, Veikko Salomaa, Giorgia Girotto, Stella Trompet, J Wouter Jukema, Pim van der Harst, Paul Ridker, Franco Giulianini, Veronique Vitart, Anuj Goel, Hugh Watkins, Sarah Harris, Ian Deary, Peter van der Most, Albertine Oldehinkel, Bernard Keavney, Caroline Hayward, Archie Campbell, Michael Boehnke, Laura Scott, Thibaud Boutin, Chrysovalanto Mamasoula, Marjo-Riitta Jarvelin, Annette Peters, Christian Gieger, Edward Lakatta, Francesco Cucca, Jennie Hui, Paul Knekt, Stefan Enroth, Martin de Borst, Ozren Polasek, Maria Pina Concas, Eulalia Catamo, Massimiliano Cocca, Ruifang Li-Gao, Edith Hofer, Helena Schmidt, Beatrice Spedicati, Melanie Waldenberger, David Strachan, Maris Laan, Alexander Teumer, Marcus Dörr, Vilmundur Gudnason, James Cook, Daniela Ruggiero, Ivana Kolcic, Eric Boerwinkle, Michela Traglia, Terho Lehtimäki, Olli Raitakari, Andrew Johnson, Christopher Newton-Cheh, Morris Brown, Anna Dominiczak, Peter Sever, Neil Poulter, John Chambers, Roberto Elosua, David Siscovick, Tōnu Esko, Andres Metspalu, Rona Strawbridge, Markku Laakso, Anders Hamsten, Jouke-Jan Hottenga, Eco de Geus, Colin Palmer, Ilja Nolte, Yuri Milaneschi, Jonathan Marten, Alan Wright, Eleftheria Zeggini, Joanna Howson, Christopher O'Donnell, Tim Spector, Mike Nalls, Eleanor Simonsick, Yongmei Liu, Cornelia van Duijn, Adam Butterworth, John Danesh, Cristina Menni, Nick Wareham, Kay Khaw, Joshua Denny, Daniel Levy, Patricia Munroe, and Harold Snieder
- Abstract
Hypertension is a leading cause of premature death affecting more than a billion individuals worldwide. Here we report on the genetic determinants of blood pressure (BP) traits (systolic, diastolic, and pulse pressure) in the largest single-stage genome-wide analysis to date (N = 1,028,980 European-descent individuals). We identified 2,103 independent genetic signals (P − 8) for BP traits, including 113 novel loci. These associations explain ~ 40% of common SNP heritability of systolic and diastolic BP. Comparison of top versus bottom deciles of polygenic risk scores (PRS) based on these results reveal clinically meaningful differences in BP (12.9 mm Hg for systolic BP, 95% CI 11.5–14.2 mm Hg, p = 9.08×10− 73) and hypertension risk (OR 5.41; 95% CI 4.12 to 7.10; P = 9.71×10− 33) in an independent dataset. Compared with the area under the curve (AUC) for hypertension discrimination for a model with sex, age, BMI, and genetic ancestry, adding systolic and diastolic BP PRS increased discrimination from 0.791 (95% CI = 0.781–0.801) to 0.814 (95% CI = 0.805–0.824, ∆AUC = 0.023, P = 2.27x10− 22). Our transcriptome-wide association study detected 2,793 BP colocalized associations with genetically-predicted expression of 1,070 genes in five cardiovascular tissues, of which 500 are previously unreported for BP traits. These findings represent an advance in our understanding of hypertension and highlight the role of increasingly large genomic studies for development of more accurate PRS, which may inform precision health research.
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- 2022
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140. Auxilin is a novel susceptibility gene for congenital heart block which directly impacts fetal heart function
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Sabrina Meisgen, Malin Hedlund, Aurelie Ambrosi, Lasse Folkersen, Vijole Ottosson, David Forsberg, Gudny Ella Thorlacius, Luca Biavati, Linn Strandberg, Johannes Mofors, Daniel Ramskold, Sabrina Ruhrmann, Lauro Meneghel, William Nyberg, Alexander Espinosa, Robert Murray Hamilton, Anders Franco-Cereceda, Anders Hamsten, Tomas Olsson, Lois Greene, Per Eriksson, Kristina Gemzell-Danielsson, Stina Salomonsson, Vijay K Kuchroo, Eric Herlenius, Ingrid Kockum, Sven-Erik Sonesson, and Marie Wahren-Herlenius
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Immunology ,Auxilins ,General Biochemistry, Genetics and Molecular Biology ,Mice ,Fetal Heart ,Heart Block ,Rheumatology ,Antibodies, Antinuclear ,Immunology and Allergy ,Animals ,Lupus Erythematosus, Systemic ,Atrioventricular Block ,Autoantibodies ,Genome-Wide Association Study - Abstract
ObjectiveNeonatal lupus erythematosus (NLE) may develop after transplacental transfer of maternal autoantibodies with cardiac manifestations (congenital heart block, CHB) including atrioventricular block, atrial and ventricular arrhythmias, and cardiomyopathies. The association with anti-Ro/SSA antibodies is well established, but a recurrence rate of only 12%–16% despite persisting maternal autoantibodies suggests that additional factors are required for CHB development. Here, we identify fetal genetic variants conferring risk of CHB and elucidate their effects on cardiac function.MethodsA genome-wide association study was performed in families with at least one case of CHB. Gene expression was analysed by microarrays, RNA sequencing and PCR and protein expression by western blot, immunohistochemistry, immunofluorescence and flow cytometry. Calcium regulation and connectivity were analysed in primary cardiomyocytes and cells induced from pleuripotent stem cells. Fetal heart performance was analysed by Doppler/echocardiography.ResultsWe identifiedDNAJC6as a novel fetal susceptibility gene, with decreased cardiac expression ofDNAJC6associated with the disease risk genotype. We further demonstrate that fetal cardiomyocytes deficient in auxilin, the protein encoded byDNAJC6, have abnormal connectivity and Ca2+homoeostasis in culture, as well as decreased cell surface expression of the Cav1.3 calcium channel. Doppler echocardiography of auxilin-deficient fetal mice revealed cardiac NLE abnormalities in utero, including abnormal heart rhythm with atrial and ventricular ectopias, as well as a prolonged atrioventricular time intervals.ConclusionsOur study identifies auxilin as the first genetic susceptibility factor in NLE modulating cardiac function, opening new avenues for the development of screening and therapeutic strategies in CHB.
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- 2022
141. The microbiome in reproductive health: protocol for a systems biology approach using a prospective, observational study design
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Maria Christine Krog, Mette Elkjær Madsen, Sofie Bliddal, Zahra Bashir, Laura Emilie Vexø, Dorthe Hartwell, Luisa W Hugerth, Emma Fransson, Marica Hamsten, Fredrik Boulund, Kristin Wannerberger, Lars Engstrand, Ina Schuppe-Koistinen, and Henriette Svarre Nielsen
- Abstract
STUDY QUESTION What is the microbiome profile across different body sites in relation to the normal menstrual cycle (with and without hormonal contraception), recurrent pregnancy loss (RPL) (before and during pregnancy, pregnancy loss or birth) and endometriosis (before, during and after surgery)? How do these profiles interact with genetics, environmental exposures, immunological and endocrine biomarkers? WHAT IS KNOWN ALREADY The microbiome is a key factor influencing human health and disease in areas as diverse as immune functioning, gastrointestinal disease and mental and metabolic disorders. There is mounting evidence to suggest that the reproductive microbiome may be influential in general and reproductive health, fertility and pregnancy outcomes. STUDY DESIGN, SIZE, DURATION This is a prospective, longitudinal, observational study using a systems biology approach in three cohorts totalling 920 participants. Since microbiome profiles by shot-gun sequencing have never been investigated in healthy controls during varying phases of the menstrual cycle, patients with RPL and patients with endometriosis, no formal sample size calculation can be performed. The study period is from 2017 to 2024 and allows for longitudinal profiling of study participants to enable deeper understanding of the role of the microbiome and of host–microbe interactions in reproductive health. PARTICIPANTS/MATERIALS, SETTING, METHODS Participants in each cohort are as follows: Part 1 MiMens—150 healthy women with or without hormonal contraception; Part 2 MiRPL—200 couples with RPL, 50 healthy couples with prior uncomplicated pregnancy and 150 newborns; Part 3 MiEndo—120 patients with endometriosis requiring surgery with or without hormonal treatment. Microbiome profiles from saliva, faeces, rectal mucosa, vaginal fluid and endometrium will be studied, as well as the Omics profile, endocrine disrupting chemicals and endocrine and immune factors in blood, hair, saliva and urine. Pregnancy loss products, seminal microbiome, HLA types, endometriotic tissue and genetic risk and comprehensive questionnaire data will also be studied, where appropriate. Correlations with mental and physical health will be evaluated. STUDY FUNDING/COMPETING INTEREST(S) This work is supported by funding from Ferring Pharmaceuticals ([#MiHSN01] to H.S.N., M.C.K., M.E.M., L.E.V., L.E., I.S.-K., F.B., L.W.H., E.F. and M.H.), Rigshospitalet’s Research Funds ([#E-22614-01 and #E-22614-02] to M.C.K. and [#E-22222-06] to S.B.), Niels and Desiree Yde’s Foundation (S.B., endocrine analyses [#2015-2784]), the Musikforlæggerne Agnes and Knut Mørk’s Foundation (S.B., endocrine and immune analyses [#35108-001]) and Oda and Hans Svenningsen’s Foundation ([#F-22614-08] to H.S.N.). Medical writing assistance with this manuscript was provided by Caroline Loat, PhD, and funded by Ferring Pharmaceuticals. H.S.N. reports personal fees from Ferring Pharmaceuticals, Merck Denmark A/S, Ibsa Nordic, Astra Zeneca and Cook Medical outside the submitted work. K.W. is a full-time employee of Ferring Pharmaceuticals. No other conflicts are reported. TRIAL REGISTRATION NUMBER N/A TRIAL REGISTRATION DATE N/A DATE OF FIRST PATIENT’S ENROLMENT N/A
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- 2022
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142. Genome-wide association study with additional genetic and post-transcriptional analyses reveals novel regulators of plasma factor XI levels
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Sennblad, Bengt, Basu, Saonli, Mazur, Johanna, Suchon, Pierre, Martinez-Perez, Angel, van Hylckama Vlieg, Astrid, Truong, Vinh, Li, Yuhuang, Gådin, Jesper R., Tang, Weihong, Grossman, Vera, de Haan, Hugoline G., Handin, Niklas, Silveira, Angela, Souto, Juan Carlos, Franco-Cereceda, Anders, Morange, Pierre-Emmanuel, Gagnon, France, Soria, Jose Manuel, Eriksson, Per, Hamsten, Anders, Maegdefessel, Lars, Rosendaal, Frits R., Wild, Philipp, Folsom, Aaron R., Trégouët, David-Alexandre, and Sabater-Lleal, Maria
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- 2017
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143. Effects of Genetic Loci Associated with Central Obesity on Adipocyte Lipolysis.
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Rona J Strawbridge, Helmut Laumen, Anders Hamsten, Michaela Breier, Harald Grallert, Hans Hauner, Peter Arner, and Ingrid Dahlman
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Medicine ,Science - Abstract
OBJECTIVES:Numerous genetic loci have been associated with measures of central fat accumulation, such as waist-to-hip ratio adjusted for body mass index (WHRadjBMI). However the mechanisms by which genetic variations influence obesity remain largely elusive. Lipolysis is a key process for regulation of lipid storage in adipocytes, thus is implicated in obesity and its metabolic complications. Here, genetic variants at 36 WHRadjBMI-associated loci were examined for their influence on abdominal subcutaneous adipocyte lipolysis. SUBJECTS AND METHODS:Fasting subcutaneous adipose tissue biopsies were collected from 789 volunteers (587 women and 202 men, body mass index (BMI) range 17.7-62.3 kg/m2). We quantified subcutaneous adipocyte lipolysis, both spontaneous and stimulated by the catecholamine isoprenaline or a cyclic AMP analogue. DNA was extracted from peripheral blood mononuclear cells and genotyping of SNPs associated with WHRadjBMI conducted. The effects on adipocyte lipolysis measures were assessed for SNPs individually and combined in a SNP score. RESULTS:The WHRadjBMI-associated loci CMIP, PLXND1, VEGFA and ZNRF3-KREMEN1 demonstrated nominal associations with spontaneous and/or stimulated lipolysis. Candidate genes in these loci have been reported to influence NFκB-signaling, fat cell size and Wnt signalling, all of which may influence lipolysis. SIGNIFICANCE:This report provides evidence for specific WHRadjBMI-associated loci as candidates to modulate adipocyte lipolysis. Additionally, our data suggests that genetically increased central fat accumulation is unlikely to be a major cause of altered lipolysis in abdominal adipocytes.
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- 2016
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144. Genetic Determinants of Thrombin Generation and Their Relation to Venous Thrombosis: Results from the GAIT-2 Project.
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Laura Martin-Fernandez, Andrey Ziyatdinov, Marina Carrasco, Juan Antonio Millon, Angel Martinez-Perez, Noelia Vilalta, Helena Brunel, Montserrat Font, Anders Hamsten, Juan Carlos Souto, and José Manuel Soria
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Medicine ,Science - Abstract
BACKGROUND:Venous thromboembolism (VTE) is a common disease where known genetic risk factors explain only a small portion of the genetic variance. Then, the analysis of intermediate phenotypes, such as thrombin generation assay, can be used to identify novel genetic risk factors that contribute to VTE. OBJECTIVES:To investigate the genetic basis of distinct quantitative phenotypes of thrombin generation and its relationship to the risk of VTE. PATIENTS/METHODS:Lag time, thrombin peak and endogenous thrombin potential (ETP) were measured in the families of the Genetic Analysis of Idiopathic Thrombophilia 2 (GAIT-2) Project. This sample consisted of 935 individuals in 35 extended families selected through a proband with idiopathic thrombophilia. We performed also genome wide association studies (GWAS) with thrombin generation phenotypes. RESULTS:The results showed that 67% of the variation in the risk of VTE is attributable to genetic factors. The heritabilities of lag time, thrombin peak and ETP were 49%, 54% and 52%, respectively. More importantly, we demonstrated also the existence of positive genetic correlations between thrombin peak or ETP and the risk of VTE. Moreover, the major genetic determinant of thrombin generation was the F2 gene. However, other suggestive signals were observed. CONCLUSIONS:The thrombin generation phenotypes are strongly genetically determined. The thrombin peak and ETP are significantly genetically correlated with the risk of VTE. In addition, F2 was identified as a major determinant of thrombin generation. We reported suggestive signals that might increase our knowledge to explain the variability of this important phenotype. Validation and functional studies are required to confirm GWAS results.
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- 2016
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145. A serum 25-hydroxyvitamin D concentration-associated genetic variant in DHCR7 interacts with type 2 diabetes status to influence subclinical atherosclerosis (measured by carotid intima–media thickness)
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Strawbridge, Rona J., Deleskog, Anna, McLeod, Olga, Folkersen, Lasse, Kavousi, Maryam, Gertow, Karl, Baldassarre, Damiano, Veglia, Fabrizio, Leander, Karin, Gigante, Bruna, Kauhanen, Jussi, Rauramaa, Rainer, Smit, Andries J., Mannarino, Elmo, Giral, Philippe, Dehghan, Abbas, Hofman, Albert, Franco, Oscar H., Humphries, Steve E., Tremoli, Elena, de Faire, Ulf, Gustafsson, Sven, Östensson, Claes-Göran, Eriksson, Per, Öhrvik, John, and Hamsten, Anders
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- 2014
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146. The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study.
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Thomas W Winkler, Anne E Justice, Mariaelisa Graff, Llilda Barata, Mary F Feitosa, Su Chu, Jacek Czajkowski, Tõnu Esko, Tove Fall, Tuomas O Kilpeläinen, Yingchang Lu, Reedik Mägi, Evelin Mihailov, Tune H Pers, Sina Rüeger, Alexander Teumer, Georg B Ehret, Teresa Ferreira, Nancy L Heard-Costa, Juha Karjalainen, Vasiliki Lagou, Anubha Mahajan, Michael D Neinast, Inga Prokopenko, Jeannette Simino, Tanya M Teslovich, Rick Jansen, Harm-Jan Westra, Charles C White, Devin Absher, Tarunveer S Ahluwalia, Shafqat Ahmad, Eva Albrecht, Alexessander Couto Alves, Jennifer L Bragg-Gresham, Anton J M de Craen, Joshua C Bis, Amélie Bonnefond, Gabrielle Boucher, Gemma Cadby, Yu-Ching Cheng, Charleston W K Chiang, Graciela Delgado, Ayse Demirkan, Nicole Dueker, Niina Eklund, Gudny Eiriksdottir, Joel Eriksson, Bjarke Feenstra, Krista Fischer, Francesca Frau, Tessel E Galesloot, Frank Geller, Anuj Goel, Mathias Gorski, Tanja B Grammer, Stefan Gustafsson, Saskia Haitjema, Jouke-Jan Hottenga, Jennifer E Huffman, Anne U Jackson, Kevin B Jacobs, Åsa Johansson, Marika Kaakinen, Marcus E Kleber, Jari Lahti, Irene Mateo Leach, Benjamin Lehne, Youfang Liu, Ken Sin Lo, Mattias Lorentzon, Jian'an Luan, Pamela A F Madden, Massimo Mangino, Barbara McKnight, Carolina Medina-Gomez, Keri L Monda, May E Montasser, Gabriele Müller, Martina Müller-Nurasyid, Ilja M Nolte, Kalliope Panoutsopoulou, Laura Pascoe, Lavinia Paternoster, Nigel W Rayner, Frida Renström, Federica Rizzi, Lynda M Rose, Kathy A Ryan, Perttu Salo, Serena Sanna, Hubert Scharnagl, Jianxin Shi, Albert Vernon Smith, Lorraine Southam, Alena Stančáková, Valgerdur Steinthorsdottir, Rona J Strawbridge, Yun Ju Sung, Ioanna Tachmazidou, Toshiko Tanaka, Gudmar Thorleifsson, Stella Trompet, Natalia Pervjakova, Jonathan P Tyrer, Liesbeth Vandenput, Sander W van der Laan, Nathalie van der Velde, Jessica van Setten, Jana V van Vliet-Ostaptchouk, Niek Verweij, Efthymia Vlachopoulou, Lindsay L Waite, Sophie R Wang, Zhaoming Wang, Sarah H Wild, Christina Willenborg, James F Wilson, Andrew Wong, Jian Yang, Loïc Yengo, Laura M Yerges-Armstrong, Lei Yu, Weihua Zhang, Jing Hua Zhao, Ehm A Andersson, Stephan J L Bakker, Damiano Baldassarre, Karina Banasik, Matteo Barcella, Cristina Barlassina, Claire Bellis, Paola Benaglio, John Blangero, Matthias Blüher, Fabrice Bonnet, Lori L Bonnycastle, Heather A Boyd, Marcel Bruinenberg, Aron S Buchman, Harry Campbell, Yii-Der Ida Chen, Peter S Chines, Simone Claudi-Boehm, John Cole, Francis S Collins, Eco J C de Geus, Lisette C P G M de Groot, Maria Dimitriou, Jubao Duan, Stefan Enroth, Elodie Eury, Aliki-Eleni Farmaki, Nita G Forouhi, Nele Friedrich, Pablo V Gejman, Bruna Gigante, Nicola Glorioso, Alan S Go, Omri Gottesman, Jürgen Gräßler, Harald Grallert, Niels Grarup, Yu-Mei Gu, Linda Broer, Annelies C Ham, Torben Hansen, Tamara B Harris, Catharina A Hartman, Maija Hassinen, Nicholas Hastie, Andrew T Hattersley, Andrew C Heath, Anjali K Henders, Dena Hernandez, Hans Hillege, Oddgeir Holmen, Kees G Hovingh, Jennie Hui, Lise L Husemoen, Nina Hutri-Kähönen, Pirro G Hysi, Thomas Illig, Philip L De Jager, Shapour Jalilzadeh, Torben Jørgensen, J Wouter Jukema, Markus Juonala, Stavroula Kanoni, Maria Karaleftheri, Kay Tee Khaw, Leena Kinnunen, Steven J Kittner, Wolfgang Koenig, Ivana Kolcic, Peter Kovacs, Nikolaj T Krarup, Wolfgang Kratzer, Janine Krüger, Diana Kuh, Meena Kumari, Theodosios Kyriakou, Claudia Langenberg, Lars Lannfelt, Chiara Lanzani, Vaneet Lotay, Lenore J Launer, Karin Leander, Jaana Lindström, Allan Linneberg, Yan-Ping Liu, Stéphane Lobbens, Robert Luben, Valeriya Lyssenko, Satu Männistö, Patrik K Magnusson, Wendy L McArdle, Cristina Menni, Sigrun Merger, Lili Milani, Grant W Montgomery, Andrew P Morris, Narisu Narisu, Mari Nelis, Ken K Ong, Aarno Palotie, Louis Pérusse, Irene Pichler, Maria G Pilia, Anneli Pouta, Myriam Rheinberger, Rasmus Ribel-Madsen, Marcus Richards, Kenneth M Rice, Treva K Rice, Carlo Rivolta, Veikko Salomaa, Alan R Sanders, Mark A Sarzynski, Salome Scholtens, Robert A Scott, William R Scott, Sylvain Sebert, Sebanti Sengupta, Bengt Sennblad, Thomas Seufferlein, Angela Silveira, P Eline Slagboom, Jan H Smit, Thomas H Sparsø, Kathleen Stirrups, Ronald P Stolk, Heather M Stringham, Morris A Swertz, Amy J Swift, Ann-Christine Syvänen, Sian-Tsung Tan, Barbara Thorand, Anke Tönjes, Angelo Tremblay, Emmanouil Tsafantakis, Peter J van der Most, Uwe Völker, Marie-Claude Vohl, Judith M Vonk, Melanie Waldenberger, Ryan W Walker, Roman Wennauer, Elisabeth Widén, Gonneke Willemsen, Tom Wilsgaard, Alan F Wright, M Carola Zillikens, Suzanne C van Dijk, Natasja M van Schoor, Folkert W Asselbergs, Paul I W de Bakker, Jacques S Beckmann, John Beilby, David A Bennett, Richard N Bergman, Sven Bergmann, Carsten A Böger, Bernhard O Boehm, Eric Boerwinkle, Dorret I Boomsma, Stefan R Bornstein, Erwin P Bottinger, Claude Bouchard, John C Chambers, Stephen J Chanock, Daniel I Chasman, Francesco Cucca, Daniele Cusi, George Dedoussis, Jeanette Erdmann, Johan G Eriksson, Denis A Evans, Ulf de Faire, Martin Farrall, Luigi Ferrucci, Ian Ford, Lude Franke, Paul W Franks, Philippe Froguel, Ron T Gansevoort, Christian Gieger, Henrik Grönberg, Vilmundur Gudnason, Ulf Gyllensten, Per Hall, Anders Hamsten, Pim van der Harst, Caroline Hayward, Markku Heliövaara, Christian Hengstenberg, Andrew A Hicks, Aroon Hingorani, Albert Hofman, Frank Hu, Heikki V Huikuri, Kristian Hveem, Alan L James, Joanne M Jordan, Antti Jula, Mika Kähönen, Eero Kajantie, Sekar Kathiresan, Lambertus A L M Kiemeney, Mika Kivimaki, Paul B Knekt, Heikki A Koistinen, Jaspal S Kooner, Seppo Koskinen, Johanna Kuusisto, Winfried Maerz, Nicholas G Martin, Markku Laakso, Timo A Lakka, Terho Lehtimäki, Guillaume Lettre, Douglas F Levinson, Lars Lind, Marja-Liisa Lokki, Pekka Mäntyselkä, Mads Melbye, Andres Metspalu, Braxton D Mitchell, Frans L Moll, Jeffrey C Murray, Arthur W Musk, Markku S Nieminen, Inger Njølstad, Claes Ohlsson, Albertine J Oldehinkel, Ben A Oostra, Lyle J Palmer, James S Pankow, Gerard Pasterkamp, Nancy L Pedersen, Oluf Pedersen, Brenda W Penninx, Markus Perola, Annette Peters, Ozren Polašek, Peter P Pramstaller, Bruce M Psaty, Lu Qi, Thomas Quertermous, Olli T Raitakari, Tuomo Rankinen, Rainer Rauramaa, Paul M Ridker, John D Rioux, Fernando Rivadeneira, Jerome I Rotter, Igor Rudan, Hester M den Ruijter, Juha Saltevo, Naveed Sattar, Heribert Schunkert, Peter E H Schwarz, Alan R Shuldiner, Juha Sinisalo, Harold Snieder, Thorkild I A Sørensen, Tim D Spector, Jan A Staessen, Bandinelli Stefania, Unnur Thorsteinsdottir, Michael Stumvoll, Jean-Claude Tardif, Elena Tremoli, Jaakko Tuomilehto, André G Uitterlinden, Matti Uusitupa, André L M Verbeek, Sita H Vermeulen, Jorma S Viikari, Veronique Vitart, Henry Völzke, Peter Vollenweider, Gérard Waeber, Mark Walker, Henri Wallaschofski, Nicholas J Wareham, Hugh Watkins, Eleftheria Zeggini, CHARGE Consortium, DIAGRAM Consortium, GLGC Consortium, Global-BPGen Consortium, ICBP Consortium, MAGIC Consortium, Aravinda Chakravarti, Deborah J Clegg, L Adrienne Cupples, Penny Gordon-Larsen, Cashell E Jaquish, D C Rao, Goncalo R Abecasis, Themistocles L Assimes, Inês Barroso, Sonja I Berndt, Michael Boehnke, Panos Deloukas, Caroline S Fox, Leif C Groop, David J Hunter, Erik Ingelsson, Robert C Kaplan, Mark I McCarthy, Karen L Mohlke, Jeffrey R O'Connell, David Schlessinger, David P Strachan, Kari Stefansson, Cornelia M van Duijn, Joel N Hirschhorn, Cecilia M Lindgren, Iris M Heid, Kari E North, Ingrid B Borecki, Zoltán Kutalik, and Ruth J F Loos
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Genetics ,QH426-470 - Abstract
Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR
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- 2015
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147. Discovering Genetic Interactions in Large-Scale Association Studies by Stage-wise Likelihood Ratio Tests.
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Mattias Frånberg, Karl Gertow, Anders Hamsten, PROCARDIS consortium, Jens Lagergren, and Bengt Sennblad
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Genetics ,QH426-470 - Abstract
Despite the success of genome-wide association studies in medical genetics, the underlying genetics of many complex diseases remains enigmatic. One plausible reason for this could be the failure to account for the presence of genetic interactions in current analyses. Exhaustive investigations of interactions are typically infeasible because the vast number of possible interactions impose hard statistical and computational challenges. There is, therefore, a need for computationally efficient methods that build on models appropriately capturing interaction. We introduce a new methodology where we augment the interaction hypothesis with a set of simpler hypotheses that are tested, in order of their complexity, against a saturated alternative hypothesis representing interaction. This sequential testing provides an efficient way to reduce the number of non-interacting variant pairs before the final interaction test. We devise two different methods, one that relies on a priori estimated numbers of marginally associated variants to correct for multiple tests, and a second that does this adaptively. We show that our methodology in general has an improved statistical power in comparison to seven other methods, and, using the idea of closed testing, that it controls the family-wise error rate. We apply our methodology to genetic data from the PROCARDIS coronary artery disease case/control cohort and discover three distinct interactions. While analyses on simulated data suggest that the statistical power may suffice for an exhaustive search of all variant pairs in ideal cases, we explore strategies for a priori selecting subsets of variant pairs to test. Our new methodology facilitates identification of new disease-relevant interactions from existing and future genome-wide association data, which may involve genes with previously unknown association to the disease. Moreover, it enables construction of interaction networks that provide a systems biology view of complex diseases, serving as a basis for more comprehensive understanding of disease pathophysiology and its clinical consequences.
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- 2015
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148. Discovery and Fine-Mapping of Glycaemic and Obesity-Related Trait Loci Using High-Density Imputation.
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Momoko Horikoshi, Reedik Mӓgi, Martijn van de Bunt, Ida Surakka, Antti-Pekka Sarin, Anubha Mahajan, Letizia Marullo, Gudmar Thorleifsson, Sara Hӓgg, Jouke-Jan Hottenga, Claes Ladenvall, Janina S Ried, Thomas W Winkler, Sara M Willems, Natalia Pervjakova, Tõnu Esko, Marian Beekman, Christopher P Nelson, Christina Willenborg, Steven Wiltshire, Teresa Ferreira, Juan Fernandez, Kyle J Gaulton, Valgerdur Steinthorsdottir, Anders Hamsten, Patrik K E Magnusson, Gonneke Willemsen, Yuri Milaneschi, Neil R Robertson, Christopher J Groves, Amanda J Bennett, Terho Lehtimӓki, Jorma S Viikari, Johan Rung, Valeriya Lyssenko, Markus Perola, Iris M Heid, Christian Herder, Harald Grallert, Martina Müller-Nurasyid, Michael Roden, Elina Hypponen, Aaron Isaacs, Elisabeth M van Leeuwen, Lennart C Karssen, Evelin Mihailov, Jeanine J Houwing-Duistermaat, Anton J M de Craen, Joris Deelen, Aki S Havulinna, Matthew Blades, Christian Hengstenberg, Jeanette Erdmann, Heribert Schunkert, Jaakko Kaprio, Martin D Tobin, Nilesh J Samani, Lars Lind, Veikko Salomaa, Cecilia M Lindgren, P Eline Slagboom, Andres Metspalu, Cornelia M van Duijn, Johan G Eriksson, Annette Peters, Christian Gieger, Antti Jula, Leif Groop, Olli T Raitakari, Chris Power, Brenda W J H Penninx, Eco de Geus, Johannes H Smit, Dorret I Boomsma, Nancy L Pedersen, Erik Ingelsson, Unnur Thorsteinsdottir, Kari Stefansson, Samuli Ripatti, Inga Prokopenko, Mark I McCarthy, Andrew P Morris, and ENGAGE Consortium
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Genetics ,QH426-470 - Abstract
Reference panels from the 1000 Genomes (1000G) Project Consortium provide near complete coverage of common and low-frequency genetic variation with minor allele frequency ≥0.5% across European ancestry populations. Within the European Network for Genetic and Genomic Epidemiology (ENGAGE) Consortium, we have undertaken the first large-scale meta-analysis of genome-wide association studies (GWAS), supplemented by 1000G imputation, for four quantitative glycaemic and obesity-related traits, in up to 87,048 individuals of European ancestry. We identified two loci for body mass index (BMI) at genome-wide significance, and two for fasting glucose (FG), none of which has been previously reported in larger meta-analysis efforts to combine GWAS of European ancestry. Through conditional analysis, we also detected multiple distinct signals of association mapping to established loci for waist-hip ratio adjusted for BMI (RSPO3) and FG (GCK and G6PC2). The index variant for one association signal at the G6PC2 locus is a low-frequency coding allele, H177Y, which has recently been demonstrated to have a functional role in glucose regulation. Fine-mapping analyses revealed that the non-coding variants most likely to drive association signals at established and novel loci were enriched for overlap with enhancer elements, which for FG mapped to promoter and transcription factor binding sites in pancreatic islets, in particular. Our study demonstrates that 1000G imputation and genetic fine-mapping of common and low-frequency variant association signals at GWAS loci, integrated with genomic annotation in relevant tissues, can provide insight into the functional and regulatory mechanisms through which their effects on glycaemic and obesity-related traits are mediated.
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- 2015
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149. CLINICAL THERAPY RESEARCH IN ALLERGIC DISEASES
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Campana, Raffaela, primary, Valenta, Rudolf, additional, Grundström, Jeanette, additional, Hamsten, Carl, additional, and van Hage, Marianne, additional
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- 2015
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150. The Feasibility of Velocity Vector Imaging by Transesophageal Echocardiography for Assessment of Elastic Properties of the Descending Aorta in Aortic Valve Disease
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Petrini, Johan, Yousry, Mohamed, Rickenlund, Anette, Liska, Jan, Hamsten, Anders, Eriksson, Per, Franco-Cereceda, Anders, Caidahl, Kenneth, and Eriksson, Maria J.
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- 2010
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