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1. COL11A1 is associated with developmental dysplasia of the hip and secondary osteoarthritis in the HUNT study

Author

Martinsen, Amy E., Skogholt, Anne Heidi, Brumpton, Ben M., Willer, Cristen J., Fors, Egil A., Kristoffersen, Espen S., Heuch, Ingrid, Mundal, Ingunn, Zwart, John-Anker, Nielsen, Jonas B., Storheim, Kjersti, Hagen, Knut, Nilsen, Kristian Bernhard, Hveem, Kristian, Fritsche, Lars G., Thomas, Laurent F., Pedersen, Linda M., Gabrielsen, Maiken E., Lie, Marie U., Stensland, Synne Ø., Zhou, Wei, Jacobsen, Kaya Kvarme, Børte, Sigrid, Laborie, Lene Bjerke, Kristiansen, Hege, Schäfer, Annette, Gundersen, Trude, Zayats, Tetyana, Slagsvold Winsvold, Bendik Kristoffer, and Rosendahl, Karen

Published
2024
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2. Genetic Risk Score for Intracranial Aneurysms: Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity

Author

Bakker, Mark K., Kanning, Jos P., Abraham, Gad, Martinsen, Amy E., Winsvold, Bendik S., Zwart, John-Anker, Bourcier, Romain, Sawada, Tomonobu, Koido, Masaru, Kamatani, Yoichiro, Morel, Sandrine, Amouyel, Philippe, Debette, Stéphanie, Bijlenga, Philippe, Berrandou, Takiy, Ganesh, Santhi K., Bouatia-Naji, Nabila, Jones, Gregory, Bown, Matthew, Rinkel, Gabriel J.E., Veldink, Jan H., Ruigrok, Ynte M., Hege Aamodt, Anne, Heidi Skogholt, Anne, Brumpton, Ben M, Willer, Cristen J, Sandset, Else C, Kristoffersen, Espen S, Ellekjær, Hanne, Heuch, Ingrid, Nielsen, Jonas B, Hagen, Knut, Hveem, Kristian, Fritsche, Lars G, Thomas, Laurent F, Pedersen, Linda M, Gabrielsen, Maiken E, Holmen, Oddgeir L, Børte, Sigrid, Zhou, Wei, Abboud, Shérine, Pandolfo, Massimo, Thijs, Vincent, Leys, Didier, Bodenant, Marie, Louillet, Fabien, Touzé, Emmanuel, Mas, Jean-Louis, Samson, Yves, Leder, Sara, Léger, Anne, Deltour, Sandrine, Crozier, Sophie, Méresse, Isabelle, Canaple, Sandrine, Godefroy, Olivier, Giroud, Maurice, Béjot, Yannick, Decavel, Pierre, Medeiros, Elizabeth, Montiel, Paola, Moulin, Thierry, Vuillier, Fabrice, Dallongeville, Jean, Metso, Antti J, Metso, Tiina, Tatlisumak, Turgut, Grond-Ginsbach, Caspar, Lichy, Christoph, Kloss, Manja, Werner, Inge, Arnold, Marie-Luise, Dos Santos, Michael, Grau, Armin, Dichgans, Martin, Thomas-Feles, Constanze, Weber, Ralf, Brandt, Tobias, Pezzini, Alessandro, De Giuli, Valeria, Caria, Filomena, Poli, Loris, Padovani, Alessandro, Bersano, Anna, Lanfranconi, Silvia, Beretta, Simone, Ferrarese, Carlo, Giacolone, Giacomo, Paolucci, Stefano, Lyrer, Philippe, Engelter, Stefan, Fluri, Felix, Hatz, Florian, Gisler, Dominique, Bonati, Leo, Gensicke, Henrik, Amort, Margareth, Markus, Hugh, Majersik, Jennifer, Worrall, Bradford, Southerland, Andrew, Cole, John, Kittner, Steven, Evangelou, Evangelos, Warren, Helen R, Gao, He, Ntritsos, Georgios, Dimou, Niki, Esko, Tonu, Mägi, Reedik, Milani, Lili, Almgren, Peter, Boutin, Thibaud, Ding, Jun, Giulianini, Franco, Holliday, Elizabeth G, Jackson, Anne U, Li-Gao, Ruifang, Lin, Wei-Yu, Luan, Jian’an, Mangino, Massimo, Oldmeadow, Christopher, Peter Prins, Bram, Qian, Yong, Sargurupremraj, Muralidharan, Shah, Nabi, Surendran, Praveen, Thériault, Sébastien, Verweij, Niek, Willems, Sara M, Zhao, Jing-Hua, Connell, John, de Mutsert, Renée, Doney, Alex SF, Farrall, Martin, Menni, Cristina, Morris, Andrew D, Noordam, Raymond, Paré, Guillaume, Poulter, Neil R, Shields, Denis C, Stanton, Alice, Thom, Simon, Abecasis, Gonçalo, Amin, Najaf, Arking, Dan E, Ayers, Kristin L, Barbieri, Caterina M, Batini, Chiara, Bis, Joshua C, Blake, Tineka, Bochud, Murielle, Boehnke, Michael, Boerwinkle, Eric, Boomsma, Dorret I, Bottinger, Erwin P, Braund, Peter S, Brumat, Marco, Campbell, Archie, Campbell, Harry, Chakravarti, Aravinda, Chambers, John C, Chauhan, Ganesh, Ciullo, Marina, Cocca, Massimiliano, Collins, Francis, Cordell, Heather J, Davies, Gail, de Borst, Martin H, de Geus, Eco J, Deary, Ian J, Deelen, Joris, Del Greco M, Fabiola, Yusuf Demirkale, Cumhur, Dörr, Marcus, Ehret, Georg B, Elosua, Roberto, Enroth, Stefan, Mesut Erzurumluoglu, A, Ferreira, Teresa, Frånberg, Mattias, Franco, Oscar H, Gandin, Ilaria, Gasparini, Paolo, Giedraitis, Vilmantas, Gieger, Christian, Girotto, Giorgia, Goel, Anuj, Gow, Alan J, Gudnason, Vilmundur, Guo, Xiuqing, Gyllensten, Ulf, Hamsten, Anders, Harris, Tamara B, Harris, Sarah E, Hartman, Catharina A, Havulinna, Aki S, Hicks, Andrew A, Hofer, Edith, Hofman, Albert, Hottenga, Jouke-Jan, Huffman, Jennifer E, Hwang, Shih-Jen, Ingelsson, Erik, James, Alan, Jansen, Rick, Jarvelin, Marjo-Riitta, Joehanes, Roby, Johansson, Åsa, Johnson, Andrew D, Joshi, Peter K, Jousilahti, Pekka, Wouter Jukema, J, Jula, Antti, Kähönen, Mika, Kathiresan, Sekar, Keavney, Bernard D, Khaw, Kay-Tee, Knekt, Paul, Knight, Joanne, Kolcic, Ivana, Kooner, Jaspal S, Koskinen, Seppo, Kristiansson, Kati, Kutalik, Zoltan, Laan, Maris, Larson, Marty, Launer, Lenore J, Lehne, Benjamin, Lehtimäki, Terho, Liewald, David CM, Lin, Li, Lind, Lars, Lindgren, Cecilia M, Liu, YongMei, Loos, Ruth JF, Lopez, Lorna M, Lu, Yingchang, Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Mamasoula, Chrysovalanto, Marrugat, Jaume, Marten, Jonathan, Milaneschi, Yuri, Morgan, Anna, Morris, Andrew P, Morrison, Alanna C, Munson, Peter J, Nalls, Mike A, Nandakumar, Priyanka, Nelson, Christopher P, Niiranen, Teemu, Nolte, Ilja M, Nutile, Teresa, Oldehinkel, Albertine J, Oostra, Ben A, O’Reilly, Paul F, Org, Elin, Padmanabhan, Sandosh, Palmas, Walter, Palotie, Aarno, Pattie, Alison, WJH Penninx, Brenda, Perola, Markus, Peters, Annette, Polasek, Ozren, Pramstaller, Peter P, Tri Nguyen, Quang, Raitakari, Olli T, Rettig, Rainer, Rice, Kenneth, Ridker, Paul M, Ried, Janina S, Riese, Harriëtte, Ripatti, Samuli, Robino, Antonietta, Rose, Lynda M, Rotter, Jerome I, Rudan, Igor, Ruggiero, Daniela, Saba, Yasaman, Sala, Cinzia F, Salomaa, Veikko, Samani, Nilesh J, Sarin, Antti-Pekka, Schmidt, Reinhold, Schmidt, Helena, Shrine, Nick, Siscovick, David, Smith, Albert V, Snieder, Harold, Sõber, Siim, Sorice, Rossella, Starr, John M, Stott, David J, Strachan, David P, Strawbridge, Rona J, Sundström, Johan, Swertz, Morris A, Taylor, Kent D, Teumer, Alexander, Tobin, Martin D, Tomaszewski, Maciej, Toniolo, Daniela, Traglia, Michela, Trompet, Stella, Tuomilehto, Jaakko, Tzourio, Christophe, Uitterlinden, André G, Vaez, Ahmad, van der Most, Peter J, van Duijn, Cornelia M, Verwoert, Germaine C, Vitart, Veronique, Völker, Uwe, Vollenweider, Peter, Vuckovic, Dragana, Watkins, Hugh, Wild, Sarah H, Willemsen, Gonneke, Wilson, James F, Wright, Alan F, Yao, Jie, Zemunik, Tatijana, Zhang, Weihua, Attia, John R, Butterworth, Adam S, Chasman, Daniel I, Conen, David, Cucca, Francesco, Danesh, John, Hayward, Caroline, Howson, Joanna MM, Laakso, Markku, Lakatta, Edward G, Langenberg, Claudia, Melander, Olle, Mook-Kanamori, Dennis O, Palmer, Colin NA, Risch, Lorenz, Scott, Robert A, Scott, Rodney J, Sever, Peter, Spector, Tim D, van der Harst, Pim, Wareham, Nicholas J, Zeggini, Eleftheria, Levy, Daniel, Munroe, Patricia B, Newton-Cheh, Christopher, Brown, Morris J, Metspalu, Andres, Psaty, Bruce M., Wain, Louise V, Elliott, Paul, Caulfield, Mark J, Gormley, Padhraig, Anttila, Verneri, Palta, Priit, Esko, Tonu, Pers, Tune H, Farh, Kai-How, Cuenca-Leon, Ester, Muona, Mikko, Furlotte, Nicholas A, Kurth, Tobias, Ingason, Andres, McMahon, George, Ligthart, Lannie, Terwindt, Gisela M, Kallela, Mikko, Freilinger, Tobias M, Ran, Caroline, Gordon, Scott G, Stam, Anine H, Steinberg, Stacy, Borck, Guntram, Koiranen, Markku, Quaye, Lydia, Adams, Hieab H H, Lehtimäki, Terho, Sarin, Antti-Pekka, Wedenoja, Juho, Hinds, David A, Buring, Julie E, Schürks, Markus, Ridker, Paul M, Gudlaug Hrafnsdottir, Maria, Stefansson, Hreinn, Ring, Susan M, Hottenga, Jouke-Jan, Penninx, Brenda W J H, Färkkilä, Markus, Artto, Ville, Kaunisto, Mari, Vepsäläinen, Salli, Malik, Rainer, Heath, Andrew C, Madden, Pamela A F, Martin, Nicholas G, Montgomery, Grant W, Kurki, Mitja I, Kals, Mart, Mägi, Reedik, Pärn, Kalle, Hämäläinen, Eija, Huang, Hailiang, Byrnes, Andrea E, Franke, Lude, Huang, Jie, Stergiakouli, Evie, Lee, Phil H, Sandor, Cynthia, Webber, Caleb, Cader, Zameel, Muller-Myhsok, Bertram, Schreiber, Stefan, Meitinger, Thomas, Eriksson, Johan G, Salomaa, Veikko, Heikkilä, Kauko, Loehrer, Elizabeth, Uitterlinden, Andre G, Hofman, Albert, van Duijn, Cornelia M, Cherkas, Lynn, Pedersen, Linda M, Stubhaug, Audun, Nielsen, Christopher S, Männikkö, Minna, Mihailov, Evelin, Milani, Lili, Göbel, Hartmut, Esserlind, Ann-Louise, Francke Christensen, Anne, Folkmann Hansen, Thomas, Werge, Thomas, Kaprio, Jaakko, Aromaa, Arpo J, Raitakari, Olli, Arfan Ikram, M, Spector, Tim, Järvelin, Marjo-Riitta, Metspalu, Andres, Kubisch, Christian, Strachan, David P, Ferrari, Michel D, Belin, Andrea C, Dichgans, Martin, Wessman, Maija, van den Maagdenberg, Arn M J M, Boomsma, Dorret I, Davey Smith, George, Stefansson, Kari, Eriksson, Nicholas, Daly, Mark J, Neale, Benjamin M, Olesen, Jes, Chasman, Daniel I, Nyholt, Dale R, Palotie, Aarno, Akiyama, Masato, Alg, Varinder S., Børte, Sigrid, Broderick, Joseph P., Brumpton, Ben M., Dauvillier, Jérôme, Desal, Hubert, Dina, Christian, Friedrich, Christoph M., Gaál-Paavola, Emília I., Gentric, Jean-Christophe, Hirsch, Sven, Hostettler, Isabel C., Houlden, Henry, Hveem, Kristian, Jääskeläinen, Juha E., Johnsen, Marianne Bakke, Li, Liming, Lin, Kuang, Lindgren, Antti, Martin, Olivier, Matsuda, Koichi, Millwood, Iona Y., Naggara, Olivier, Niemelä, Mika, Pera, Joanna, Redon, Richard, Rouleau, Guy A., Sandvei, Marie Søfteland, Schilling, Sabine, Shotar, Eimad, Slowik, Agnieszka, Terao, Chikashi, Verschuren, W. M. Monique, Walters, Robin G., Werring, David J., Willer, Cristen J., Woo, Daniel, Worrall, Bradford B., and Zhou, Sirui

Published
2023
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3. A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease

Author

Wightman, Douglas P., Jansen, Iris E., Savage, Jeanne E., Shadrin, Alexey A., Bahrami, Shahram, Holland, Dominic, Rongve, Arvid, Børte, Sigrid, Winsvold, Bendik S., Drange, Ole Kristian, Martinsen, Amy E., Skogholt, Anne Heidi, Willer, Cristen, Bråthen, Geir, Bosnes, Ingunn, Nielsen, Jonas Bille, Fritsche, Lars G., Thomas, Laurent F., Pedersen, Linda M., Gabrielsen, Maiken E., Johnsen, Marianne Bakke, Meisingset, Tore Wergeland, Zhou, Wei, Proitsi, Petroula, Hodges, Angela, Dobson, Richard, Velayudhan, Latha, Heilbron, Karl, Auton, Adam, Sealock, Julia M., Davis, Lea K., Pedersen, Nancy L., Reynolds, Chandra A., Karlsson, Ida K., Magnusson, Sigurdur, Stefansson, Hreinn, Thordardottir, Steinunn, Jonsson, Palmi V., Snaedal, Jon, Zettergren, Anna, Skoog, Ingmar, Kern, Silke, Waern, Margda, Zetterberg, Henrik, Blennow, Kaj, Stordal, Eystein, Hveem, Kristian, Zwart, John-Anker, Athanasiu, Lavinia, Selnes, Per, Saltvedt, Ingvild, Sando, Sigrid B., Ulstein, Ingun, Djurovic, Srdjan, Fladby, Tormod, Aarsland, Dag, Selbæk, Geir, Ripke, Stephan, Stefansson, Kari, Andreassen, Ole A., and Posthuma, Danielle

Published
2021
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4. Author Correction: A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease

Author

Wightman, Douglas P., Jansen, Iris E., Savage, Jeanne E., Shadrin, Alexey A., Bahrami, Shahram, Holland, Dominic, Rongve, Arvid, Børte, Sigrid, Winsvold, Bendik S., Drange, Ole Kristian, Martinsen, Amy E., Skogholt, Anne Heidi, Willer, Cristen, Bråthen, Geir, Bosnes, Ingunn, Nielsen, Jonas Bille, Fritsche, Lars G., Thomas, Laurent F., Pedersen, Linda M., Gabrielsen, Maiken E., Johnsen, Marianne Bakke, Meisingset, Tore Wergeland, Zhou, Wei, Proitsi, Petroula, Hodges, Angela, Dobson, Richard, Velayudhan, Latha, Heilbron, Karl, Auton, Adam, Sealock, Julia M., Davis, Lea K., Pedersen, Nancy L., Reynolds, Chandra A., Karlsson, Ida K., Magnusson, Sigurdur, Stefansson, Hreinn, Thordardottir, Steinunn, Jonsson, Palmi V., Snaedal, Jon, Zettergren, Anna, Skoog, Ingmar, Kern, Silke, Waern, Margda, Zetterberg, Henrik, Blennow, Kaj, Stordal, Eystein, Hveem, Kristian, Zwart, John-Anker, Athanasiu, Lavinia, Selnes, Per, Saltvedt, Ingvild, Sando, Sigrid B., Ulstein, Ingun, Djurovic, Srdjan, Fladby, Tormod, Aarsland, Dag, Selbæk, Geir, Ripke, Stephan, Stefansson, Kari, Andreassen, Ole A., and Posthuma, Danielle

Published
2022
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5. Author Correction: A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease

Author

Wightman, Douglas P., Jansen, Iris E., Savage, Jeanne E., Shadrin, Alexey A., Bahrami, Shahram, Holland, Dominic, Rongve, Arvid, Børte, Sigrid, Winsvold, Bendik S., Drange, Ole Kristian, Martinsen, Amy E., Skogholt, Anne Heidi, Willer, Cristen, Bråthen, Geir, Bosnes, Ingunn, Nielsen, Jonas Bille, Fritsche, Lars G., Thomas, Laurent F., Pedersen, Linda M., Gabrielsen, Maiken E., Johnsen, Marianne Bakke, Meisingset, Tore Wergeland, Zhou, Wei, Proitsi, Petroula, Hodges, Angela, Dobson, Richard, Velayudhan, Latha, Heilbron, Karl, Auton, Adam, Sealock, Julia M., Davis, Lea K., Pedersen, Nancy L., Reynolds, Chandra A., Karlsson, Ida K., Magnusson, Sigurdur, Stefansson, Hreinn, Thordardottir, Steinunn, Jonsson, Palmi V., Snaedal, Jon, Zettergren, Anna, Skoog, Ingmar, Kern, Silke, Waern, Margda, Zetterberg, Henrik, Blennow, Kaj, Stordal, Eystein, Hveem, Kristian, Zwart, John-Anker, Athanasiu, Lavinia, Selnes, Per, Saltvedt, Ingvild, Sando, Sigrid B., Ulstein, Ingun, Djurovic, Srdjan, Fladby, Tormod, Aarsland, Dag, Selbæk, Geir, Ripke, Stephan, Stefansson, Kari, Andreassen, Ole A., and Posthuma, Danielle

Published
2021
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8. Cerebral small vessel disease genomics and its implications across the lifespan

Author

Sargurupremraj, Muralidharan, Suzuki, Hideaki, Zhao, Wei, Okada, Yukinori, Mazoyer, Bernard, Wardlaw, Joanna M, Nyquist, Paul A, Mather, Karen A, Grabe, Hans, Schmidt, Helena, Van Duijn, Cornelia M, Gudnason, Vilmundur, Longstreth, William T, Armstrong, Nicola J, Launer, Lenore J, Lathrop, Mark, Seshadri, Sudha, Tzourio, Christophe, Adams, Hieab H, Matthews, Paul M, Fornage, Myriam, Debette, Stéphanie, Amouyel, Philippe, de Andrade, Mariza, Hofer, Edith, Basu, Saonli, Berr, Claudine, Brody, Jennifer A, Chasman, Daniel I, Dartigues, Jean-Francois, Folsom, Aaron R, Germain, Marine, de Haan, Hugoline, Heit, John, Houwing-Duitermaat, Jeanine, Yanek, Lisa R, Kabrhel, Christopher, Kraft, Peter, Legal, Grégoire, Lindström, Sara, Monajemi, Ramin, Morange, Pierre-Emmanuel, Psaty, Bruce M, Reitsma, Pieter H, Ridker, Paul M, Rose, Lynda M, Hagenaars, Saskia P, Rosendaal, Frits R, Saut, Noémie, Slagboom, Eline, Smadja, David, Smith, Nicholas L, Suchon, Pierre, Tang, Weihong, Taylor, Kent D, Trégouët, David-Alexandre, Kumar, Rajan B, de Visser, Marieke C H, van Hylckama Vlieg, Astrid, Weng, Lu-Chen, Wiggins, Kerri L, Gormley, Padhraig, Anttila, Verneri, Winsvold, Bendik S, Palta, Priit, Esko, Tonu, Pers, Tune H, van den Akker, Erik B, Farh, Kai-How, Cuenca-Leon, Ester, Muona, Mikko, Furlotte, Nicholas A, Kurth, Tobias, Ingason, Andres, McMahon, George, Ligthart, Lannie, Terwindt, Gisela M, Kallela, Mikko, McWhirter, Rebekah E, Freilinger, Tobias M, Ran, Caroline, Gordon, Scott G, Stam, Anine H, Steinberg, Stacy, Borck, Guntram, Koiranen, Markku, Quaye, Lydia, Adams, Hieab H H, Lehtimäki, Terho, Trompet, Stella, Sarin, Antti-Pekka, Wedenoja, Juho, Hinds, David A, Buring, Julie E, Schürks, Markus, Gudlaug Hrafnsdottir, Maria, Stefansson, Hreinn, Ring, Susan M, Hottenga, Jouke-Jan, Mishra, Aniket, Penninx, Brenda W J H, Färkkilä, Markus, Artto, Ville, Kaunisto, Mari, Vepsäläinen, Salli, Malik, Rainer, Heath, Andrew C, Madden, Pamela A F, Martin, Nicholas G, Montgomery, Grant W, Jian, Xueqiu, Saba, Yasaman, Kurki, Mitja, Kals, Mart, Mägi, Reedik, Pärn, Kalle, Hämäläinen, Eija, Huang, Hailiang, Byrnes, Andrea E, Franke, Lude, Huang, Jie, Stergiakouli, Evie, Satizabal, Claudia L, Lee, Phil H, Sandor, Cynthia, Webber, Caleb, Cader, Zameel, Muller-Myhsok, Bertram, Schreiber, Stefanie, Meitinger, Thomas, Eriksson, Johan G, Salomaa, Veikko, Heikkilä, Kauko, Beaudet, Gregory, Loehrer, Elizabeth, Uitterlinden, Andre G, Hofman, Albert, van Duijn, Cornelia M, Cherkas, Lynn, Pedersen, Linda M, Stubhaug, Audun, Nielsen, Christopher S, Männikkö, Minna, Mihailov, Evelin, Petit, Laurent, Milani, Lili, Göbel, Hartmut, Esserlind, Ann-Louise, Francke Christensen, Anne, Folkmann Hansen, Thomas, Werge, Thomas, Kaprio, Jaakko, Aromaa, Arpo J, Raitakari, Olli, Ikram, M Arfan, Tsuchida, Ami, Spector, Tim, Järvelin, Marjo-Riitta, Metspalu, Andres, Kubisch, Christian, Strachan, David P, Ferrari, Michel D, Belin, Andrea C, Dichgans, Martin, Wessman, Maija, van den Maagdenberg, Arn M J M, Zago, Laure, Zwart, John-Anker, Boomsma, Dorret I, Davey Smith, George, Stefansson, Kari, Eriksson, Nicholas, Daly, Mark J, Neale, Benjamin M, Olesen, Jes, Nyholt, Dale R, Schilling, Sabrina, Palotie, Aarno, Sigurdsson, Sigurdur, Gottesman, Rebecca F, Lewis, Cora E, Sarnowski, Chloé, Aggarwal, Neelum T, Lopez, Oscar L, Smith, Jennifer A, Valdés Hernández, Maria C, van der Grond, Jeroen, Wright, Margaret J, Knol, Maria J, Dörr, Marcus, Thomson, Russell J, Bordes, Constance, Evans, Tavia E, Le Grand, Quentin, Duperron, Marie-Gabrielle, Smith, Albert V, Knopman, David S, Schreiner, Pamela J, Evans, Denis A, Rotter, Jerome I, Beiser, Alexa S, Maniega, Susana Muñoz, Beekman, Marian, Bis, Joshua C, Trollor, Julian, Stott, David J, Vernooij, Meike W, Wittfeld, Katharina, Niessen, Wiro J, Soumaré, Aicha, Boerwinkle, Eric, Sidney, Stephen, Turner, Stephen T, Davies, Gail, Eiriksdottir, Gudny, Thalamuthu, Anbupalam, Völker, Uwe, van Buchem, Mark A, Bryan, R Nick, Dupuis, Josée, Bastin, Mark E, Ames, David, Teumer, Alexander, Kwok, John B, Sakaue, Saori, Bülow, Robin, Deary, Ian J, Schofield, Peter R, Brodaty, Henry, Jiang, Jiyang, Tabara, Yasuharu, Setoh, Kazuya, Miyamoto, Susumu, Yoshida, Kazumichi, Nagata, Manabu, Terzikhan, Natalie, Kamatani, Yoichiro, Matsuda, Fumihiko, Bennett, David A, De Jager, Philip L, Mosley, Thomas H, Sachdev, Perminder S, Schmidt, Reinhold, Warren, Helen R, Evangelou, Evangelos, Habes, Mohamad, Thrombosis, International Network against, Consortium, International Headache Genomics, Ikram, Mohammad A, Wen, Wei, DeCarli, Charles, Srikanth, Velandai K, Jukema, J Wouter, Slagboom, Eline P, Kardia, Sharon L R, Equipe VINTAGE - Inserm U1219 [Bordeaux], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe d'imagerie neurofonctionnelle (GIN), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), and Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)

Subjects
Adult, Male, epidemiology [Alzheimer Disease], genetics [Alzheimer Disease], diagnosis [Cerebral Small Vessel Diseases], epidemiology [Hypertension], Genome-wide association studies, behavioral disciplines and activities, Risk Assessment, Article, diagnostic imaging [White Matter], Young Adult, Alzheimer Disease, Risk Factors, White matter disease, mental disorders, Humans, Medical History Taking, Aged, Aged, 80 and over, [SCCO.NEUR]Cognitive science/Neuroscience, Mendelian Randomization Analysis, Middle Aged, White Matter, Stroke, Diffusion Tensor Imaging, Genetic Loci, Cerebral Small Vessel Diseases, complications [Cerebral Small Vessel Diseases], Hypertension, genetics [Stroke], genetics [Cerebral Small Vessel Diseases], Female, genetics [Hypertension], ddc:500, epidemiology [Stroke], Genome-Wide Association Study
Abstract

White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials., White matter hyperintensities (WMH) are a common brain-imaging feature of cerebral small vessel disease. Here, the authors carry out a GWAS and followup analyses for WMH-volume, implicating several variants with potential for risk stratification and drug targeting.

Published
2020

9. A genome-wide cross-phenotype meta-analysis of the association of blood pressure with migraine

Author

Guo, Yanjun, Rist, Pamela M., Daghlas, Iyas, Giulianini, Franco, Gormley, Padhraig, Anttila, Verneri, Winsvold, Bendik S., Palta, Priit, Esko, Tonu, Pers, Tune H., Farh, Kai How, Cuenca-Leon, Ester, Muona, Mikko, Furlotte, Nicholas A., Kurth, Tobias, Ingason, Andres, McMahon, George, Ligthart, Lannie, Terwindt, Gisela M., Kallela, Mikko, Freilinger, Tobias M., Ran, Caroline, Gordon, Scott G., Stam, Anine H., Steinberg, Stacy, Borck, Guntram, Koiranen, Markku, Quaye, Lydia, Adams, Hieab H.H., Lehtimäki, Terho, Sarin, Antti Pekka, Wedenoja, Juho, Hinds, David A., Buring, Julie E., Schürks, Markus, Ridker, Paul M., Hrafnsdottir, Maria Gudlaug, Stefansson, Hreinn, Ring, Susan M., Hottenga, Jouke Jan, Penninx, Brenda W.J.H., Färkkilä, Markus, Artto, Ville, Kaunisto, Mari, Vepsäläinen, Salli, Malik, Rainer, Heath, Andrew C., Madden, Pamela A.F., Martin, Nicholas G., Montgomery, Grant W., Kurki, Mitja, Kals, Mart, Mägi, Reedik, Pärn, Kalle, Hämäläinen, Eija, Huang, Hailiang, Byrnes, Andrea E., Franke, Lude, Huang, Jie, Stergiakouli, Evie, Lee, Phil H., Sandor, Cynthia, Webber, Caleb, Cader, Zameel, Muller-Myhsok, Bertram, Schreiber, Stefan, Meitinger, Thomas, Eriksson, Johan G., Salomaa, Veikko, Heikkilä, Kauko, Loehrer, Elizabeth, Uitterlinden, Andre G., Hofman, Albert, Duijn, Cornelia M.van, Cherkas, Lynn, Pedersen, Linda M., Stubhaug, Audun, Nielsen, Christopher S., Männikkö, Minna, Mihailov, Evelin, Milani, Lili, Göbel, Hartmut, Esserlind, Ann Louise, Christensen, Anne Francke, Hansen, Thomas Folkmann, Werge, Thomas, Kaprio, Jaakko, Aromaa, Arpo J., Raitakari, Olli, Ikram, M. Arfan, Spector, Tim, Järvelin, Marjo Riitta, Metspalu, Andres, Kubisch, Christian, Strachan, David P., Ferrari, Michel D., Belin, Andrea C., Dichgans, Martin, Wessman, Maija, Maagdenberg, Arn M.J.M.van den, Zwart, John Anker, Boomsma, Dorret I., Smith, George Davey, Stefansson, Kari, Eriksson, Nicholas, Daly, Mark J., Neale, Benjamin M., Olesen, Jes, Chasman, Daniel I., Nyholt, Dale R., Palotie, Aarno, Agee, Michelle, Auton, Adam, Bell, Robert K., Bryc, Katarzyna, Elson, Sarah L., Fontanillas, Pierre, Huber, Karen E., Kleinman, Aaron, Litterman, Nadia K., McCreight, Jennifer C., McIntyre, Matthew H., Mountain, Joanna L., Noblin, Elizabeth S., Northover, Carrie A.M., Pitts, Steven J., Sathirapongsasuti, J. Fah, Sazonova, Olga V., Shelton, Janie F., Shringarpure, Suyash, Tian, Chao, Tung, Joyce Y., Vacic, Vladimir, Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, APH - Mental Health, Amsterdam Neuroscience - Complex Trait Genetics, Psychiatry, APH - Digital Health, Radiology & Nuclear Medicine, Epidemiology, Neurology, Internal Medicine, Biological Psychology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, APH - Methodology, Clinicum, Neurologian yksikkö, HUS Neurocenter, HUS Helsinki and Uusimaa Hospital District, Department of Neurosciences, Research Programs Unit, Institute for Molecular Medicine Finland, Neuroscience Center, STEMM - Stem Cells and Metabolism Research Program, Genomics of Neurological and Neuropsychiatric Disorders, Department of Public Health, Biosciences, Centre of Excellence in Complex Disease Genetics, Research Programme of Molecular Medicine, Aarno Palotie / Principal Investigator, Helsinki University Hospital Area, University of Helsinki, Johan Eriksson / Principal Investigator, and Department of General Practice and Primary Health Care

Subjects
0301 basic medicine, Netherlands Twin Register (NTR), Integrin beta Chains, LOCI, Medizin, General Physics and Astronomy, Blood Pressure, Genome-wide association study, Genome-wide association studies, DISEASE, 3124 Neurology and psychiatry, 0302 clinical medicine, HEADACHE, Risk Factors, Polymorphism (computer science), Genome-wide, lcsh:Science, Telomerase, Multidisciplinary, Mendelian Randomization Analysis, Blóðþrýstingur, 3. Good health, Pulse pressure, Mígreni, Hypertension, Blood pressure, Cross-phenotype, Erfðarannsóknir, medicine.medical_specialty, Migraine Disorders, Science, Diastole, Polymorphism, Single Nucleotide, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Meta-Analysis as Topic, SDG 3 - Good Health and Well-being, Receptors, Adrenergic, alpha-2, Internal medicine, Mendelian randomization, medicine, Humans, Genetic Predisposition to Disease, Migraine, business.industry, Proteins, General Chemistry, medicine.disease, Meta-analysis, 030104 developmental biology, Endocrinology, RISK-FACTORS, lcsh:Q, business, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Publisher's version (útgefin grein), Blood pressure (BP) was inconsistently associated with migraine and the mechanisms of BP-lowering medications in migraine prophylaxis are unknown. Leveraging large-scale summary statistics for migraine (Ncases/Ncontrols = 59,674/316,078) and BP (N = 757,601), we find positive genetic correlations of migraine with diastolic BP (DBP, rg = 0.11, P = 3.56 × 10−06) and systolic BP (SBP, rg = 0.06, P = 0.01), but not pulse pressure (PP, rg = −0.01, P = 0.75). Cross-trait meta-analysis reveals 14 shared loci (P ≤ 5 × 10−08), nine of which replicate (P, This research has been conducted using the UK Biobank Resource under Application Number 29273. We would like to thank the participants and researchers from the UK Biobank, 23andMe, Inc., International Headache Genetics Consortium (IHGC), MEGASTROKE, CARDIoGRAM, and International Consortium of Blood Pressure-Genome Wide Association Studies (ICBP) who contributed or collected data. Daniel I. Chasman is funded by US National Institutes of Health and US National Institute of Neurological Disorders and Stroke (R21NS09296 and R21NS104398). Pamela M. Rist is funded by K01 HL128791. The MEGASTROKE project received funding from sources specified at http://www.megastroke.org/acknowledgments.html.

Published
2020

10. Molecular genetic overlap between migraine and major depressive disorder

Author

Yang, Yuanhao, Zhao, Huiying, Boomsma, Dorret I, Smith, George Davey, Esko, Tonu, Hansen, Thomas Folkmann, Ikram, M. Arfan, Paraskevi, Christofidou, Strachan, David P., Wessman, Maija, Gormley, Padhraig, Anttila, Verneri, Winsvold, Bendik S., Palta, Priit, Pers, Tune H., Farh, Kai-How, Cuenca-Leon, Ester, Muona, Mikko, Furlotte, Nicholas A., Kurth, Tobias, Ingason, Andres, McMahon, George, Ligthart, Lannie, Kallela, Mikko, Freilinger, Tobias M., Ran, Caroline, Gordon, Scott G., Stam, Anine H., Steinberg, Stacy, Borck, Guntram, Koiranen, Markku, Quaye, Lydia, Adams, Hieab H. H., Lehtimäki, Terho, Sarin, Antti-Pekka, Wedenoja, Juho, Hinds, David A., Buring, Julie E., Schürks, Markus, Ridker, Paul M., Hrafnsdottir, Maria Gudlaug, Stefansson, Hreinn, Ring, Susan M., Hottenga, Jouke-Jan, Penninx, Brenda W. J. H., Färkkilä, Markus, Artto, Ville, Kaunisto, Mari, Vepsäläinen, Salli, Malik, Rainer, Heath, Andrew C., Madden, Pamela A. F., Martin, Nicholas G., Montgomery, Grant W, Kurki, Mitja I, Kals, Mart, Mägi, Reedik, Pärn, Kalle, Hämäläinen, Eija, Huang, Hailiang, Byrnes, Andrea E., Franke, Lude, Huang, Jie, Stergiakouli, Evie, Lee, Phil H., Sandor, Cynthia, Webber, Caleb, Cader, Zameel, Muller-Myhsok, Bertram, Schreiber, Stefan, Meitinger, Thomas, Eriksson, Johan G., Salomaa, Veikko, Heikkilä, Kauko, Loehrer, Elizabeth, Uitterlinden, Andre G., Hofman, Albert, van Duijn, Cornelia M., Cherkas, Lynn, Pedersen, Linda M., Stubhaug, Audun, Nielsen, Christopher S., Männikkö, Minna, Mihailov, Evelin, Milani, Lili, Göbel, Hartmut, Esserlind, Ann-Louise, Christensen, Anne Francke, Werge, Thomas, Kaprio, Jaakko, Aromaa, Arpo J., Raitakari, Olli, Spector, Tim, Järvelin, Marjo-Riitta, Metspalu, Andres, Kubisch, Christian, Ferrari, Michel D., Belin, Andrea C., Dichgans, Martin, Zwart, John-Anker, Stefansson, Kari, Eriksson, Nicholas, Daly, Mark J., Neale, Benjamin M., Olesen, Jes, Chasman, Daniel I., Nyholt, Dale R., Palotie, Aarno, van den Maagdenberg, Arn M. J. M., Terwindt, Gisela M., Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, Epidemiology, Biological Psychology, APH - Methodology, APH - Personalized Medicine, and APH - Health Behaviors & Chronic Diseases

Subjects
0301 basic medicine, Netherlands Twin Register (NTR), Linkage disequilibrium, Migraine Disorders, Medizin, Single-nucleotide polymorphism, Genome-wide association study, Polymorphism, Single Nucleotide, Article, Linkage Disequilibrium, 03 medical and health sciences, 0302 clinical medicine, Potassium Channels, Tandem Pore Domain, SDG 3 - Good Health and Well-being, Genotype, Databases, Genetic, Genetics, medicine, SNP, Humans, Genetics (clinical), Depressive Disorder, Major, business.industry, medicine.disease, Comorbidity, Ankyrin Repeat, 030104 developmental biology, Migraine, Major depressive disorder, business, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Migraine and major depressive disorder (MDD) are common brain disorders that frequently co-occur. Despite epidemiological evidence that migraine and MDD share a genetic basis, their overlap at the molecular genetic level has not been thoroughly investigated. Using single-nucleotide polymorphism (SNP) and gene-based analysis of genome-wide association study (GWAS) genotype data, we found significant genetic overlap across the two disorders. LD Score regression revealed a significant SNP-based heritability for both migraine (h2= 12%) and MDD (h2= 19%), and a significant cross-disorder genetic correlation (rG= 0.25; P = 0.04). Meta-analysis of results for 8,045,569 SNPs from a migraine GWAS (comprising 30,465 migraine cases and 143,147 control samples) and the top 10,000 SNPs from a MDD GWAS (comprising 75,607 MDD cases and 231,747 healthy controls), implicated three SNPs (rs146377178, rs672931, and rs11858956) with novel genome-wide significant association (PSNP≤ 5 × 10−8) to migraine and MDD. Moreover, gene-based association analyses revealed significant enrichment of genes nominally associated (Pgene-based≤ 0.05) with both migraine and MDD (Pbinomial-test= 0.001). Combining results across migraine and MDD, two genes, ANKDD1B and KCNK5, produced Fisher’s combined gene-based P values that surpassed the genome-wide significance threshold (PFisher’s-combined≤ 3.6 × 10−6). Pathway analysis of genes with PFisher’s-combined≤ 1 × 10−3suggested several pathways, foremost neural-related pathways of signalling and ion channel regulation, to be involved in migraine and MDD aetiology. In conclusion, our study provides strong molecular genetic support for shared genetically determined biological mechanisms underlying migraine and MDD.

Published
2018

11. The association between selected genetic variants and individual differences in experimental pain.

Author

Lie, Marie Udnesseter, Winsvold, Bendik, Gjerstad, Johannes, Matre, Dagfinn, Pedersen, Linda M., Heuch, Ingrid, Zwart, John-Anker, and Nilsen, Kristian Bernhard

Abstract

Objectives: The underlying mechanisms for individual differences in experimental pain are not fully understood, but genetic susceptibility is hypothesized to explain some of these differences. In the present study we focus on three genetic variants important for modulating experimental pain related to serotonin (SLC6A4 5-HTTLPR/rs25531 A>G), catecholamine (COMT rs4680 Val158Met) and opioid (OPRM1 rs1799971 A118G) signaling. We aimed to investigate associations between each of the selected genetic variants and individual differences in experimental pain. Methods: In total 356 subjects (232 low back pain patients and 124 healthy volunteers) were genotyped and assessed with tests of heat pain threshold, pressure pain thresholds, heat pain tolerance, conditioned pain modulation (CPM), offset analgesia, temporal summation and secondary hyperalgesia. Low back pain patients and healthy volunteers did not differ in regards to experimental test results or allelic frequencies, and were therefore analyzed as one group. The associations were tested using analysis of variance and the Kruskal-Wallis test. Results: No significant associations were observed between the genetic variants (SLC6A4 5-HTTLPR/rs25531 A>G, COMT rs4680 Val158Met and OPRM1 rs1799971 A118G) and individual differences in experimental pain (heat pain threshold, pressure pain threshold, heat pain tolerance, CPM, offset analgesia, temporal summation and secondary hyperalgesia). Conclusions: The selected pain-associated genetic variants were not associated with individual differences in experimental pain. Genetic variants well known for playing central roles in pain perception failed to explain individual differences in experimental pain in 356 subjects. The finding is an important contribution to the literature, which often consists of studies with lower sample size and one or few experimental pain assessments. [ABSTRACT FROM AUTHOR]

Published
2021
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12. Predicting the outcome of persistent sciatica using conditioned pain modulation: 1-year results from a prospective cohort study.

Author

Fjeld, Olaf R., Grotle, Margreth, Matre, Dagfinn, Pedersen, Linda M., Lie, Marie U., Småstuen, Milada C., Storheim, Kjersti, Heuch, Ingrid, Stubhaug, Audun, Zwart, John-Anker, and Nilsen, Kristian Bernhard

Abstract

Background and aims: Recovery in patients hospitalised with severe sciatica is unpredictable. Prognostic tools to aid clinicians in the early identification of patients at risk of developing chronic sciatic pain are warranted. Conditioned pain modulation (CPM) is a psychophysical measure of the endogenous pain modulatory pathways. Several studies have suggested CPM as a potentially important predictive biomarker for the development of chronic pain. The aim of the study was to determine whether CPM effect in patients still suffering from leg pain 6 weeks after hospital discharge for severe sciatica is associated with persistent leg pain at 12 months. A potential association would suggest that measuring CPM effect could be a valuable prognostic tool in the hospital management of sciatica. Methods: A prospective cohort study in which CPM effect was measured 6 weeks after hospital discharge following an acute admission with sciatica as the main complaint. The impact of CPM effect on the outcome was analysed using logistic regression. The outcome measured was self-reported leg pain score of ≥1 in the past week on a 0–10 numeric rating scale (NRS) at 12 months post discharge. Results: A total of 111 patients completed the entire study, 51 of whom received non-randomised surgical treatment. Crude and confounder adjusted analyses showed no significant association between CPM effect and leg-pain measured at 12 months, crude Odds Ratio 0.87, 95% CI 0.7–1.1, p = 0.23. Conclusions: Our results suggest that CPM assessment has limited prognostic value for the long-term outcome in severe sciatica when measured 6 weeks after hospital discharge. Implications: The present study adds important knowledge concerning the limited clinical use of late CPM testing in sciatica patients. The heterogeneity in patients, the wide range of treatments received and a generally favourable outcome are factors that may affect CPM's clinical value as a prognostic factor for severe sciatica. [ABSTRACT FROM AUTHOR]

Published
2020
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13. Antibiotic treatment In patients with chronic low back pain and Modic changes (the AIM study): study protocol for a randomised controlled trial.

Author

Storheim, Kjersti, Espeland, Ansgar, Grøvle, Lars, Skouen, Jan Sture, Aßmus, Jörg, Anke, Audny, Froholdt, Anne, Pedersen, Linda M., Haugen, Anne Julsrud, Fors, Terese, Schistad, Elina, Lutro, Olav, Marchand, Gunn Hege, Kadar, Thomas, Vetti, Nils, Randen, Sigrun, Nygaard, Øystein Petter, Brox, Jens Ivar, Grotle, Margreth, and Zwart, John-Anker

Subjects
RANDOMIZED controlled trials, MEDICAL care, BACKACHE, ANTIBIOTICS, BONE marrow
Abstract

Background: A previous randomised controlled trial (RCT) of patients with chronic low back pain (LBP) and vertebral bone marrow (Modic) changes (MCs) on magnetic resonance imaging (MRI), reported that a 3-month, high-dose course of antibiotics had a better effect than placebo at 12 months' follow-up. The present study examines the effects of antibiotic treatment in chronic LBP patients with MCs at the level of a lumbar disc herniation, similar to the previous study. It also aims to assess the cost-effectiveness of the treatment, refine the MRI assessment of MCs, and further evaluate the impact of the treatment and the pathogenesis of MCs by studying genetic variability and the gene and protein expression of inflammatory biomarkers.Methods/design: A double-blinded RCT is conducted at six hospitals in Norway, comparing orally administered amoxicillin 750 mg, or placebo three times a day, over a period of 100 days in patients with chronic LBP and type I or II MCs at the level of a MRI-confirmed lumbar disc herniation within the preceding 2 years. The inclusion will be stopped when at least 80 patients are included in each of the two MC type groups. In each MC type group, the study is designed to detect (β = 0.1, α = 0.05) a mean difference of 4 (standard deviation 5) in the Roland Morris Disability Questionnaire score between the two treatment groups (amoxicillin or placebo) at 1-year follow-up. The study includes cost-effectiveness measures. Blood samples are assessed for security measures and for possible inflammatory mediators and biomarkers at different time points. MCs are evaluated on MRI at baseline and after 12 months. A blinded intention-to-treat analysis of treatment effects will be performed in the total sample and in each MC type group.Discussion: To ensure the appropriate use of antibiotic treatment, its effect in chronic LBP patients with MCs should be re-assessed. This study will investigate the effects and cost-effectiveness of amoxicillin in patients with chronic LBP and MCs at the level of a disc herniation. The study may also help to refine imaging and characterise the biomarkers of MCs.Trial Registration: ClinicalTrials.gov, ID: NCT02323412 . Registered on 21 November 2014. [ABSTRACT FROM AUTHOR]

Published
2017
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16. Catechol-O-methyltransferase (COMT) inhibition reduces spinal nociceptive activity

Author

Jacobsen, Line M., Eriksen, Guro S., Pedersen, Linda M., and Gjerstad, Johannes

Subjects
*ENZYME inhibitors, *CATECHOL, *METHYLTRANSFERASES, *SPINAL cord, *GENE expression, *CATECHOLAMINES, *MATHEMATICAL models
Abstract

Abstract: Several variants of the catechol-O-methyltransferase (COMT) gene have recently been linked to pain sensitivity. In the present study, electrophysiological field potential recordings from the dorsal horn in rats were used to examine the spinal effect of reduced COMT activity. The data demonstrated that 30mg/kg of the COMT inhibitor OR 486 reduced spinal nociceptive responses to painful stimuli (p ≤0.01, OR 486 vs. vehicle) and attenuated the expression of spinal long-term potentiation (LTP), an often studied model for central sensitization (p ≤0.01, HFS vs. HFS+OR 486). Our findings suggest that low COMT activity may have an antinociceptive effect in the spinal cord. [Copyright &y& Elsevier]

Published
2010
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17. Publisher Correction : Stroke genetics informs drug discovery and risk prediction across ancestries

Author

Mishra, Aniket, Malik, Rainer, He, Yunye, 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, Georgakis, Marios K, 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, Caro, Ilana, Trégouët, David-Alexandre, Trompet, Stella, Tuladhar, Anil Man, Tybjærg-Hansen, Anne, van Vugt, Marion, Vibo, Riina, Verma, Shefali S, Wiggins, Kerri L, Wennberg, Patrik, Woo, Daniel, Krebs, Kristi, Wilson, Peter W F, Xu, Huichun, Yang, Qiong, Yoon, Kyungheon, Consortium, COMPASS, Consortium, INVENT, Initiative, Dutch Parelsnoer, Biobank, Estonian, Consortium, PRECISE4Q, Consortium, FinnGen, Liaw, Yi-Ching, Network, NINDS Stroke Genetics, Consortium, MEGASTROKE, Consortium, SIREN, Group, China Kadoorie Biobank Collaborative, Program, VA Million Veteran, Consortium, International Stroke Genetics, Japan, Biobank, Consortium, CHARGE, Consortium, GIGASTROKE, Millwood, Iona Y, Vaura, Felix C, 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 M M, Lin, Kuang, Irvin, Marguerite R, Adams, Hieab, Wassertheil-Smoller, Sylvia, Christensen, Kaare, Ikram, Mohammad A, Rundek, Tatjana, Worrall, Bradford B, Lathrop, G Mark, Riaz, Moeen, Simonsick, Eleanor M, Winsvold, Bendik Slagsvold, Kõrv, Janika, França, Paulo H C, Zand, Ramin, Prasad, Kameshwar, Frikke-Schmidt, Ruth, de Leeuw, Frank-Erik, Liman, Thomas G., Haeusler, Karl Georg, Ruigrok, Ynte M, Heuschmann, Peter Ulrich, Srinivasasainagendra, Vinodh, Longstreth, W. T., Jung, Keum Ji, Bastarache, Lisa, Paré, Guillaume, Damrauer, Scott M, Chasman, Daniel I, Rotter, Jerome I, Anderson, Christopher D, Zwart, John-Anker, Niiranen, Teemu J, Parodi, Livia, Fornage, Myriam, Liaw, Yung-Po, Seshadri, Sudha, Fernández-Cadenas, Israel, Walters, Robin G, Ruff, Christian T, Owolabi, Mayowa O, Huffman, Jennifer E, Milani, Lili, Kamatani, Yoichiro, Hachiya, Tsuyoshi, Bae, Hee-Joon, Dichgans, Martin, Debette, Stephanie, Chauhan, Ganesh, Chong, Michael R, Tomppo, Liisa, Akinyemi, Rufus, Roshchupkin, Gennady V, Habib, Naomi, Jee, Yon Ho, Thomassen, Jesper Qvist, Abedi, Vida, Jürgenson, Tuuli, Cárcel-Márquez, Jara, Nygaard, Marianne, Leonard, Hampton L, Yang, Chaojie, Yonova-Doing, Ekaterina, Knol, Maria J, Lewis, Adam J, Judy, Renae L, Ago, Tetsuro, Amouyel, Philippe, Namba, Shinichi, Armstrong, Nicole D, Bakker, Mark K, Bartz, Traci M, Bennett, David A, Bis, Joshua C, Bordes, Constance, Børte, Sigrid, Cain, Anael, Ridker, Paul M, Cho, Kelly, Posner, Daniel C, 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, Kamanu, Frederick K, 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, Koido, Masaru, Jern, Christina, Kamouchi, Masahiro, Keene, Keith L, Kitazono, Takanari, Kittner, Steven J, Konuma, Takahiro, Kumar, Amit, Lacaze, Paul, Launer, Lenore J, Lee, Keon-Joo, Le Grand, Quentin, Lepik, Kaido, Li, Jiang, Li, Liming, Manichaikul, Ani, Markus, Hugh S, Marston, Nicholas A, Meitinger, Thomas, Mitchell, Braxton D, Montellano, Felipe A, Morisaki, Takayuki, Shi, Mingyang, Mosley, Thomas H, Nalls, Mike A, Nordestgaard, Børge G, O'Donnell, Martin J, Okada, Yukinori, Onland-Moret, N Charlotte, Ovbiagele, Bruce, Peters, Annette, Psaty, Bruce M, Rich, Stephen S, Bis, Joshua C, Lee, Jin-Moo, Cheng, Yu-Ching, Meschia, James F, Chen, Wei Min, Sale, Michèle 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-François, 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 J H, Kappelle, L Jaap, Esko, Tõnu, Metspalu, Andres, Mägi, Reedik, Nelis, Mari, Irvin, Marguerite R, de Leeuw, Frank-Erik, Levi, Christopher R, Maguire, Jane, Jiménez-Conde, Jordi, Sharma, Pankaj, Sudlow, Cathie L M, Rannikmäe, Kristiina, Schmidt, Reinhold, Slowik, Agnieszka, Pera, Joanna, Thijs, Vincent N S, Lindgren, Arne G, Ilinca, Andreea, Melander, Olle, Engström, 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, Ibañez, Laura, Krupinski, Jerzy, Lioutas, Vasileios, Matsuda, Koichi, Montaner, Joan, Muiño, 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 I W, 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-François, Delavaran, Hossein, Dörr, 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, Müller-Nurasyid, Martina, Norrving, Bo, Ogishima, Soichi, Parati, Eugenio A, Pedersen, Nancy L, Perola, Markus, Jousilahti, Pekka, Pileggi, Silvana, Rabionet, Raquel, Riba-Llena, Iolanda, Ribasés, Marta, Romero, Jose R, Rudd, Anthony G, Sarin, Antti-Pekka, Sarju, Ralhan, Satoh, Mamoru, Sawada, Norie, Sigurdsson, Ásgeir, 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 D A, Wong, Quenna, Yamaji, Taiki, Sanghera, Dharambir K, Stefansson, Kari, Martinez-Majander, Nicolas, Sobue, Kenji, Soriano-Tárraga, Carolina, Völzke, 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, Le Grand, Quentin, Ferreira, Leslie E, Nagai, Akiko, Murakami, Yoishinori, Geerlings, Mirjam I, Gasca, Natalie C, Gudnason, Vilmundur, van Vugt, Marion, Shiroma, Eric J, Sigurdsson, Sigurdur, Ghanbari, Mohsen, Boerwinkle, Eric, Fongang, Bernard, Wang, Ruiqi, Ikram, Mohammad K, Völker, Uwe, de Jager, Phil L, de Cid, Rafael, Nordestgaard, Børge G, Sargurupremraj, Muralidharan, Verma, Shefali S, de Laat, Karlijn F, van Norden, Anouk G W, de Kort, Paul L, Vermeer, Sarah E, Brouwers, Paul J A M, Gons, Rob A R, den Heijer, Tom, van Dijk, Gert W, van Rooij, Frank G W, Aamodt, Anne H, Skogholt, Anne H, Willer, Cristen J, Heuch, Ingrid, Hagen, Knut, Fritsche, Lars G, Pedersen, Linda M, Ellekjær, Hanne, Zhou, Wei, Martinsen, Amy E, Kristoffersen, Espen S, Thomas, Laurent F, Kleinschnitz, Christoph, Frantz, Stefan, Ungethüm, Kathrin, Gallego-Fabrega, Cristina, Lledós, Miquel, Llucià-Carol, Laia, Sobrino, Tomas, Campos, Francisco, Castillo, José, Freijó, Marimar, Arenillas, Juan Francisco, Obach, Victor, Álvarez-Sabín, José, Molina, Carlos A, Ribó, Marc, Muñoz-Narbona, Lucia, Lopez-Cancio, Elena, Millán, Mònica, Diaz-Navarro, Rosa, Vives-Bauza, Cristòfol, Serrano-Heras, Gemma, Segura, Tomás, Dhar, Rajat, Delgado-Mederos, Raquel, Prats-Sánchez, Luis, Camps-Renom, Pol, Blay, Natalia, Sumoy, Lauro, Martí-Fàbregas, Joan, Schnohr, Peter, Jensen, Gorm B, Benn, Marianne, Afzal, Shoaib, Kamstrup, Pia R, van Setten, Jessica, van der Laan, Sander W, Vonk, Jet M J, Kim, Bong-Jo, Curtze, Sami, Tiainen, Marjaana, Kinnunen, Janne, Menon, Vilas, Sung, Yun Ju, Yang, Chengran, Saillour-Glenisson, Florence, Gravel, Simon, Onland-Moret, N Charlotte, and Heath, Alicia K

Subjects
Stroke, Multidisciplinary, Genetic markers, ddc:500, Predictive markers, Genome-wide association studies
Published
2022

18. Inhibition of fatty acid amide hydrolase (FAAH) reduces spinal nociceptive responses and expression of spinal long-term potentiation (LTP)

Author

Eriksen, Guro S., Jacobsen, Line Melå, Mahmood, Aqsa, Pedersen, Linda M., and Gjerstad, Johannes

Subjects
*CANNABINOIDS, *POLYMERASE chain reaction, *OPIOID receptors, *HYPERALGESIA, *NALOXONE, *ENZYME inhibitors
Abstract

Abstract: Fatty acid amide hydrolase (FAAH) is an enzyme that metabolizes endocannabinoids and fatty acid amides possibly linked to activation of the opioid system. To examine how this enzyme affects spinal signalling, electrophysiological recordings in the dorsal horn and qPCR on dorsal horn tissue following systemic administration of the FAAH inhibitor URB597 (0.3 and 1.0mg/kg i.v.) and spinal administration of the opioid receptor antagonist naloxone (0.1μg/μl i.th.), were performed. The present data showed that the suppressive effect of the FAAH inhibitor URB597 (1.0mg/kg i.v.) on the spinal nociceptive responses was prevented by spinal administration of the opioid receptor antagonist naloxone (0.1μg/μl i.th.). Moreover, the present findings demonstrated that the FAAH inhibitor URB597 (1.0mg/kg i.v.) partly reversed expression of spinal long-term potentiation (LTP) and also attenuated the LTP-associated increased Zif expression. We conclude that pharmacological inactivation of FAAH may be a promising strategy to inhibit the development of central hyperalgesia; thereby reinforcing the role of FAAH as a potential therapeutic target. [Copyright &y& Elsevier]

Published
2012
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19. The association between selected genetic variants and individual differences in experimental pain.

Author

Lie MU, Winsvold B, Gjerstad J, Matre D, Pedersen LM, Heuch I, Zwart JA, and Nilsen KB

Subjects
Humans, Pain Threshold, Polymorphism, Single Nucleotide, Serotonin Plasma Membrane Transport Proteins, Catechol O-Methyltransferase genetics, Individuality, Pain genetics, Receptors, Opioid, mu genetics
Abstract

Objectives: The underlying mechanisms for individual differences in experimental pain are not fully understood, but genetic susceptibility is hypothesized to explain some of these differences. In the present study we focus on three genetic variants important for modulating experimental pain related to serotonin (SLC6A4 5-HTTLPR/rs25531 A>G), catecholamine (COMT rs4680 Val158Met) and opioid (OPRM1 rs1799971 A118G) signaling. We aimed to investigate associations between each of the selected genetic variants and individual differences in experimental pain., Methods: In total 356 subjects (232 low back pain patients and 124 healthy volunteers) were genotyped and assessed with tests of heat pain threshold, pressure pain thresholds, heat pain tolerance, conditioned pain modulation (CPM), offset analgesia, temporal summation and secondary hyperalgesia. Low back pain patients and healthy volunteers did not differ in regards to experimental test results or allelic frequencies, and were therefore analyzed as one group. The associations were tested using analysis of variance and the Kruskal-Wallis test., Results: No significant associations were observed between the genetic variants (SLC6A4 5-HTTLPR/rs25531 A>G, COMT rs4680 Val158Met and OPRM1 rs1799971 A118G) and individual differences in experimental pain (heat pain threshold, pressure pain threshold, heat pain tolerance, CPM, offset analgesia, temporal summation and secondary hyperalgesia)., Conclusions: The selected pain-associated genetic variants were not associated with individual differences in experimental pain. Genetic variants well known for playing central roles in pain perception failed to explain individual differences in experimental pain in 356 subjects. The finding is an important contribution to the literature, which often consists of studies with lower sample size and one or few experimental pain assessments., (© 2020 Walter de Gruyter GmbH, Berlin/Boston.)

Published
2020
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20. Predicting the outcome of persistent sciatica using conditioned pain modulation: 1-year results from a prospective cohort study.

Author

Fjeld OR, Grotle M, Matre D, Pedersen LM, Lie MU, Småstuen MC, Storheim K, Heuch I, Stubhaug A, Zwart JA, and Nilsen KB

Subjects
Adult, Female, Hospitalization, Humans, Longitudinal Studies, Male, Middle Aged, Prospective Studies, Surveys and Questionnaires, Pain complications, Pain Measurement, Prognosis, Sciatica surgery, Sciatica therapy
Abstract

Background and aims Recovery in patients hospitalised with severe sciatica is unpredictable. Prognostic tools to aid clinicians in the early identification of patients at risk of developing chronic sciatic pain are warranted. Conditioned pain modulation (CPM) is a psychophysical measure of the endogenous pain modulatory pathways. Several studies have suggested CPM as a potentially important predictive biomarker for the development of chronic pain. The aim of the study was to determine whether CPM effect in patients still suffering from leg pain 6 weeks after hospital discharge for severe sciatica is associated with persistent leg pain at 12 months. A potential association would suggest that measuring CPM effect could be a valuable prognostic tool in the hospital management of sciatica. Methods A prospective cohort study in which CPM effect was measured 6 weeks after hospital discharge following an acute admission with sciatica as the main complaint. The impact of CPM effect on the outcome was analysed using logistic regression. The outcome measured was self-reported leg pain score of ≥1 in the past week on a 0-10 numeric rating scale (NRS) at 12 months post discharge. Results A total of 111 patients completed the entire study, 51 of whom received non-randomised surgical treatment. Crude and confounder adjusted analyses showed no significant association between CPM effect and leg-pain measured at 12 months, crude Odds Ratio 0.87, 95% CI 0.7-1.1, p = 0.23. Conclusions Our results suggest that CPM assessment has limited prognostic value for the long-term outcome in severe sciatica when measured 6 weeks after hospital discharge. Implications The present study adds important knowledge concerning the limited clinical use of late CPM testing in sciatica patients. The heterogeneity in patients, the wide range of treatments received and a generally favourable outcome are factors that may affect CPM's clinical value as a prognostic factor for severe sciatica.

Published
2019
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21. Corrigendum: Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine.

Author

Gormley P, Anttila V, Winsvold BS, Palta P, Esko T, Pers TH, Farh KH, Cuenca-Leon E, Muona M, Furlotte NA, Kurth T, Ingason A, McMahon G, Ligthart L, Terwindt GM, Kallela M, Freilinger TM, Ran C, Gordon SG, Stam AH, Steinberg S, Borck G, Koiranen M, Quaye L, Adams HH, Lehtimäki T, Sarin AP, Wedenoja J, Hinds DA, Buring JE, Schürks M, Ridker PM, Hrafnsdottir MG, Stefansson H, Ring SM, Hottenga JJ, Penninx BW, Färkkilä M, Artto V, Kaunisto M, Vepsäläinen S, Malik R, Heath AC, Madden PA, Martin NG, Montgomery GW, Kurki MI, Kals M, Mägi R, Pärn K, Hämäläinen E, Huang H, Byrnes AE, Franke L, Huang J, Stergiakouli E, Lee PH, Sandor C, Webber C, Cader Z, Muller-Myhsok B, Schreiber S, Meitinger T, Eriksson JG, Salomaa V, Heikkilä K, Loehrer E, Uitterlinden AG, Hofman A, van Duijn CM, Cherkas L, Pedersen LM, Stubhaug A, Nielsen CS, Männikkö M, Mihailov E, Milani L, Göbel H, Esserlind AL, Christensen AF, Hansen TF, Werge T, Kaprio J, Aromaa AJ, Raitakari O, Ikram MA, Spector T, Järvelin MR, Metspalu A, Kubisch C, Strachan DP, Ferrari MD, Belin AC, Dichgans M, Wessman M, van den Maagdenberg AM, Zwart JA, Boomsma DI, Smith GD, Stefansson K, Eriksson N, Daly MJ, Neale BM, Olesen J, Chasman DI, Nyholt DR, and Palotie A

Published
2016
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22. Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine.

Author

Gormley P, Anttila V, Winsvold BS, Palta P, Esko T, Pers TH, Farh KH, Cuenca-Leon E, Muona M, Furlotte NA, Kurth T, Ingason A, McMahon G, Ligthart L, Terwindt GM, Kallela M, Freilinger TM, Ran C, Gordon SG, Stam AH, Steinberg S, Borck G, Koiranen M, Quaye L, Adams HH, Lehtimäki T, Sarin AP, Wedenoja J, Hinds DA, Buring JE, Schürks M, Ridker PM, Hrafnsdottir MG, Stefansson H, Ring SM, Hottenga JJ, Penninx BW, Färkkilä M, Artto V, Kaunisto M, Vepsäläinen S, Malik R, Heath AC, Madden PA, Martin NG, Montgomery GW, Kurki MI, Kals M, Mägi R, Pärn K, Hämäläinen E, Huang H, Byrnes AE, Franke L, Huang J, Stergiakouli E, Lee PH, Sandor C, Webber C, Cader Z, Muller-Myhsok B, Schreiber S, Meitinger T, Eriksson JG, Salomaa V, Heikkilä K, Loehrer E, Uitterlinden AG, Hofman A, van Duijn CM, Cherkas L, Pedersen LM, Stubhaug A, Nielsen CS, Männikkö M, Mihailov E, Milani L, Göbel H, Esserlind AL, Christensen AF, Hansen TF, Werge T, Kaprio J, Aromaa AJ, Raitakari O, Ikram MA, Spector T, Järvelin MR, Metspalu A, Kubisch C, Strachan DP, Ferrari MD, Belin AC, Dichgans M, Wessman M, van den Maagdenberg AM, Zwart JA, Boomsma DI, Smith GD, Stefansson K, Eriksson N, Daly MJ, Neale BM, Olesen J, Chasman DI, Nyholt DR, and Palotie A

Subjects
Case-Control Studies, Genome-Wide Association Study, Genomics, Humans, Muscle, Smooth metabolism, Vascular Diseases genetics, Genetic Loci genetics, Genetic Markers genetics, Genetic Predisposition to Disease, Migraine Disorders genetics, Polymorphism, Single Nucleotide genetics
Abstract

Migraine is a debilitating neurological disorder affecting around one in seven people worldwide, but its molecular mechanisms remain poorly understood. There is some debate about whether migraine is a disease of vascular dysfunction or a result of neuronal dysfunction with secondary vascular changes. Genome-wide association (GWA) studies have thus far identified 13 independent loci associated with migraine. To identify new susceptibility loci, we carried out a genetic study of migraine on 59,674 affected subjects and 316,078 controls from 22 GWA studies. We identified 44 independent single-nucleotide polymorphisms (SNPs) significantly associated with migraine risk (P < 5 × 10(-8)) that mapped to 38 distinct genomic loci, including 28 loci not previously reported and a locus that to our knowledge is the first to be identified on chromosome X. In subsequent computational analyses, the identified loci showed enrichment for genes expressed in vascular and smooth muscle tissues, consistent with a predominant theory of migraine that highlights vascular etiologies.

Published
2016
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23. Genetic analysis for a shared biological basis between migraine and coronary artery disease.

Author

Winsvold BS, Nelson CP, Malik R, Gormley P, Anttila V, Vander Heiden J, Elliott KS, Jacobsen LM, Palta P, Amin N, de Vries B, Hämäläinen E, Freilinger T, Ikram MA, Kessler T, Koiranen M, Ligthart L, McMahon G, Pedersen LM, Willenborg C, Won HH, Olesen J, Artto V, Assimes TL, Blankenberg S, Boomsma DI, Cherkas L, Davey Smith G, Epstein SE, Erdmann J, Ferrari MD, Göbel H, Hall AS, Jarvelin MR, Kallela M, Kaprio J, Kathiresan S, Lehtimäki T, McPherson R, März W, Nyholt DR, O'Donnell CJ, Quaye L, Rader DJ, Raitakari O, Roberts R, Schunkert H, Schürks M, Stewart AF, Terwindt GM, Thorsteinsdottir U, van den Maagdenberg AM, van Duijn C, Wessman M, Kurth T, Kubisch C, Dichgans M, Chasman DI, Cotsapas C, Zwart JA, Samani NJ, and Palotie A

Abstract

Objective: To apply genetic analysis of genome-wide association data to study the extent and nature of a shared biological basis between migraine and coronary artery disease (CAD)., Methods: Four separate methods for cross-phenotype genetic analysis were applied on data from 2 large-scale genome-wide association studies of migraine (19,981 cases, 56,667 controls) and CAD (21,076 cases, 63,014 controls). The first 2 methods quantified the extent of overlapping risk variants and assessed the load of CAD risk loci in migraineurs. Genomic regions of shared risk were then identified by analysis of covariance patterns between the 2 phenotypes and by querying known genome-wide significant loci., Results: We found a significant overlap of genetic risk loci for migraine and CAD. When stratified by migraine subtype, this was limited to migraine without aura, and the overlap was protective in that patients with migraine had a lower load of CAD risk alleles than controls. Genes indicated by 16 shared risk loci point to mechanisms with potential roles in migraine pathogenesis and CAD, including endothelial dysfunction (PHACTR1) and insulin homeostasis (GIP)., Conclusions: The results suggest that shared biological processes contribute to risk of migraine and CAD, but surprisingly this commonality is restricted to migraine without aura and the impact is in opposite directions. Understanding the mechanisms underlying these processes and their opposite relationship to migraine and CAD may improve our understanding of both disorders.

Published
2015
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24. Changes in gene expression of Zif, c-fos and cyclooxygenase-2 associated with spinal long-term potentiation.

Author

Gjerstad J, Lien GF, Pedersen LM, Valen EC, and Mollerup S

Subjects
Animals, Cyclooxygenase 2, Early Growth Response Protein 1, Electrophysiology, Female, Gene Expression physiology, Genes, Immediate-Early physiology, RNA, Messenger analysis, Rats, Rats, Sprague-Dawley, DNA-Binding Proteins genetics, Immediate-Early Proteins genetics, Long-Term Potentiation physiology, Prostaglandin-Endoperoxide Synthases genetics, Proto-Oncogene Proteins c-fos genetics, Spinal Cord physiology, Transcription Factors genetics
Abstract

Spinal cord long-term potentiation is often studied as a model for cellular memory of nociceptive information. In the present report, extracellular single-unit recordings and quantitative real-time reverse transcriptase polymerase chain reaction were used to examine whether the induction of spinal cord long-term potentiation involves changes in expression of Zif, c-fos and cyclooxygenase-2. The data demonstrated that induction of spinal cord long-term potentiation was associated with a transient increase in the expression of Zif at 120 min (p < 0.05, long-term potentiation group vs. control group). In contrast, a decrease or no changes were observed in the expression of c-fos and cyclooxygenase-2. The transient increase of the expression of Zif is consistent with an involvement in the transition from the early to the late-phase of spinal cord long-term potentiation.

Published
2005
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