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2. Konsensusstatement der Migräne- und Kopfschmerzgesellschaften (DMKG, ÖKSG & SKG) zur Therapiedauer der medikamentösen Migräneprophylaxe

Author

Goßrau, Gudrun, Förderreuther, Stefanie, Ruscheweyh, Ruth, Ruschil, Victoria, Sprenger, Till, Lewis, David, Kamm, Katharina, Freilinger, Tobias, Neeb, Lars, Malzacher, Volker, Meier, Uwe, Gehring, Klaus, Kraya, Torsten, Dresler, Thomas, Schankin, Christoph J., Gantenbein, Andreas R., Brössner, Gregor, Zebenholzer, Karin, Diener, Hans-Christoph, Gaul, Charly, and Jürgens, Tim P.

Published
2023
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3. Neurologic manifestations of COVID-19 in critically ill patients: results of the prospective multicenter registry PANDEMIC

Author

Dimitriadis, Konstantinos, Meis, Jan, Neugebauer, Hermann, Barlinn, Kristian, Neumann, Bernhard, Gahn, Georg, Lochner, Piergiorgio, Knier, Benjamin, Lindemann, Sarah, Sühs, Kurt Wolfram, Szabo, Kristina, Pfefferkorn, Thomas, Schirotzek, Ingo, Freilinger, Tobias, Burc, Bassa, Günther, Albrecht, Wittstock, Matthias, Schramm, Patrick, Reimann, Gernot, Godau, Jana, Nagy, Gabor, Koenig, Fatima B., Essig, Fabian, Klinker, Hartwig, Hartmann, Christian, Schmidbauer, Moritz L., Steinberg, Tim, Lefterova, Lora, Klose, Christina, and Bösel, Julian

Published
2022
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4. Erratum zu: Konsensusstatement der Migräne- und Kopfschmerzgesellschaften (DMKG, ÖKSG & SKG) zur Therapiedauer der medikamentösen Migräneprophylaxe

Author

Goßrau, Gudrun, Förderreuther, Stefanie, Ruscheweyh, Ruth, Ruschil, Victoria, Sprenger, Till, Lewis, David, Kamm, Katharina, Freilinger, Tobias, Neeb, Lars, Malzacher, Volker, Meier, Uwe, Gehring, Klaus, Kraya, Torsten, Dresler, Thomas, Schankin, Christoph J., Gantenbein, Andreas R., Brössner, Gregor, Zebenholzer, Karin, Diener, Hans-Christoph, Gaul, Charly, and Jürgens, Tim P.

Published
2023
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5. Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles

Author

Hautakangas, Heidi, Winsvold, Bendik S., Ruotsalainen, Sanni E., Bjornsdottir, Gyda, Harder, Aster V. E., Kogelman, Lisette J. A., Thomas, Laurent F., Noordam, Raymond, Benner, Christian, Gormley, Padhraig, Artto, Ville, Banasik, Karina, Bjornsdottir, Anna, Boomsma, Dorret I., Brumpton, Ben M., Burgdorf, Kristoffer Sølvsten, Buring, Julie E., Chalmer, Mona Ameri, de Boer, Irene, Dichgans, Martin, Erikstrup, Christian, Färkkilä, Markus, Garbrielsen, Maiken Elvestad, Ghanbari, Mohsen, Hagen, Knut, Häppölä, Paavo, Hottenga, Jouke-Jan, Hrafnsdottir, Maria G., Hveem, Kristian, Johnsen, Marianne Bakke, Kähönen, Mika, Kristoffersen, Espen S., Kurth, Tobias, Lehtimäki, Terho, Lighart, Lannie, Magnusson, Sigurdur H., Malik, Rainer, Pedersen, Ole Birger, Pelzer, Nadine, Penninx, Brenda W. J. H., Ran, Caroline, Ridker, Paul M., Rosendaal, Frits R., Sigurdardottir, Gudrun R., Skogholt, Anne Heidi, Sveinsson, Olafur A., Thorgeirsson, Thorgeir E., Ullum, Henrik, Vijfhuizen, Lisanne S., Widén, Elisabeth, van Dijk, Ko Willems, Aromaa, Arpo, Belin, Andrea Carmine, Freilinger, Tobias, Ikram, M. Arfan, Järvelin, Marjo-Riitta, Raitakari, Olli T., Terwindt, Gisela M., Kallela, Mikko, Wessman, Maija, Olesen, Jes, Chasman, Daniel I., Nyholt, Dale R., Stefánsson, Hreinn, Stefansson, Kari, van den Maagdenberg, Arn M. J. M., Hansen, Thomas Folkmann, Ripatti, Samuli, Zwart, John-Anker, Palotie, Aarno, and Pirinen, Matti

Published
2022
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6. 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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7. Shared genetic risk between migraine and coronary artery disease: A genome-wide analysis of common variants.

Author

Winsvold, Bendik S, Bettella, Francesco, Witoelar, Aree, Anttila, Verneri, Gormley, Padhraig, Kurth, Tobias, Terwindt, Gisela M, Freilinger, Tobias M, Frei, Oleksander, Shadrin, Alexey, Wang, Yunpeng, Dale, Anders M, van den Maagdenberg, Arn MJM, Chasman, Daniel I, Nyholt, Dale R, Palotie, Aarno, Andreassen, Ole A, Zwart, John-Anker, and International Headache Genetics Consortium

Subjects
International Headache Genetics Consortium, Humans, Genetic Predisposition to Disease, Phenotype, Polymorphism, Single Nucleotide, Female, Male, Migraine Disorders, Coronary Artery Disease, Genome-Wide Association Study, General Science & Technology
Abstract

Migraine is a recurrent pain condition traditionally viewed as a neurovascular disorder, but little is known of its vascular basis. In epidemiological studies migraine is associated with an increased risk of cardiovascular disease, including coronary artery disease (CAD), suggesting shared pathogenic mechanisms. This study aimed to determine the genetic overlap between migraine and CAD, and to identify shared genetic risk loci, utilizing a conditional false discovery rate approach and data from two large-scale genome-wide association studies (GWAS) of CAD (C4D, 15,420 cases, 15,062 controls; CARDIoGRAM, 22,233 cases, 64,762 controls) and one of migraine (22,120 cases, 91,284 controls). We found significant enrichment of genetic variants associated with CAD as a function of their association with migraine, which was replicated across two independent CAD GWAS studies. One shared risk locus in the PHACTR1 gene (conjunctional false discovery rate for index SNP rs9349379 < 3.90 x 10-5), which was also identified in previous studies, explained much of the enrichment. Two further loci (in KCNK5 and AS3MT) showed evidence for shared risk (conjunctional false discovery rate < 0.05). The index SNPs at two of the three loci had opposite effect directions in migraine and CAD. Our results confirm previous reports that migraine and CAD share genetic risk loci in excess of what would be expected by chance, and highlight one shared risk locus in PHACTR1. Understanding the biological mechanisms underpinning this shared risk is likely to improve our understanding of both disorders.

Published
2017

8. Safety and efficacy of prednisone versus placebo in short-term prevention of episodic cluster headache: a multicentre, double-blind, randomised controlled trial

Author

Obermann, Mark, Nägel, Steffen, Ose, Claudia, Sonuc, Nilüfer, Scherag, André, Storch, Peter, Gaul, Charly, Böger, Andreas, Kraya, Torsten, Jansen, Jan-Peter, Straube, Andreas, Freilinger, Tobias, Kaube, Holger, Jürgens, Tim P, Diener, Hans-Christoph, Katsarava, Zaza, Kleinschnitz, Christoph, and Holle, Dagny

Published
2021
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9. Zoonotic spillover infections with Borna disease virus 1 leading to fatal human encephalitis, 1999–2019: an epidemiological investigation

Author

Niller, Hans Helmut, Angstwurm, Klemens, Rubbenstroth, Dennis, Schlottau, Kore, Ebinger, Arnt, Giese, Sebastian, Wunderlich, Silke, Banas, Bernhard, Forth, Leonie F, Hoffmann, Donata, Höper, Dirk, Schwemmle, Martin, Tappe, Dennis, Schmidt-Chanasit, Jonas, Nobach, Daniel, Herden, Christiane, Brochhausen, Christoph, Velez-Char, Natalia, Mamilos, Andreas, Utpatel, Kirsten, Evert, Matthias, Zoubaa, Saida, Riemenschneider, Markus J, Ruf, Viktoria, Herms, Jochen, Rieder, Georg, Errath, Mario, Matiasek, Kaspar, Schlegel, Jürgen, Liesche-Starnecker, Friederike, Neumann, Bernhard, Fuchs, Kornelius, Linker, Ralf A, Salzberger, Bernd, Freilinger, Tobias, Gartner, Lisa, Wenzel, Jürgen J, Reischl, Udo, Jilg, Wolfgang, Gessner, André, Jantsch, Jonathan, Beer, Martin, and Schmidt, Barbara

Published
2020
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10. Genome wide association study identifies variants in NBEA associated with migraine in bipolar disorder

Author

Jacobsen, Kaya K, Nievergelt, Caroline M, Zayats, Tetyana, Greenwood, Tiffany A, Anttila, Verneri, Akiskal, Hagop S, Consortium, BiGS, Consortium, IHG, include:, BiGS Consortium Co-Authors, Kelsoe, John R, McKinney, Rebecca, Shilling, Paul D, Smith, Erin N, Schork, Nicholas J, Bloss, Cinnamon S, Nurnberger, John I, Edenberg, Howard J, Foroud, Tatiana, Koller, Daniel L, Gershon, Elliot S, Badner, Judith A, Liu, Chunyu, Scheftner, William A, Lawson, William B, Nwulia, Evaristus A, Hipolito, Maria, Potash, James, Coryell, William, Rice, John, Byerley, William, McMahon, Francis J, Berrettini, Wade H, Zandi, Peter P, Mahon, Pamela B, McInnis, Melvin G, Zöllner, Sebastian, Zhang, Peng, Craig, David W, Szelinger, Szabolics, Barrett, Thomas B, Schulze, Thomas G, include:, IHG Consortium Co-Authors, Wedenoja, Juho, Kaunisto, Mari A, Heikkilä, Kauko, Kaprio, Jaakko, Wessman, Maija, Kallela, Mikko, Färkkilä, Markus, Artto, Ville, Aromaa, Arpo, Eriksson, Johan G, Winsvold, Bendik S, Zwart, John-Anker, Gormley, Padhraig, Palotie, Aarno, Kurth, Tobias, Rose, Lynda M, Buring, Julie E, Ridker, Paul M, Chasman, Daniel I, Bettella, Francesco, Steinberg, Stacy, Stefansson, Hreinn, Stefansson, Kari, McMahon, George, Davey-Smith, George, Malik, Rainer, Freilinger, Tobias, Wichmann, Heinz Erich, Dichgans, Martin, Muller-Myhsok, Bertram, Meitinger, Thomas, de Vries, Boukje, Terwindt, Gisela, Stam, Anine H, Frants, Rune R, Pelzer, Nadine, Weller, Claudia M, Zielman, Ronald, Ferrari, Michel D, van den Maagdenberg, Arn MJM, Medland, Sarah E, Montgomery, Grant W, Martin, Nicholas G, Nyholt, Dale R, Todt, Unda, Borck, Guntram, Kubisch, Christian, Quaye, Lydia, Williams, Frances MK, Cherkas, Lynn, Koiranen, Markku, Hartikainen, Anna-Liisa, Pouta, Anneli, Jarvelin, Marjo-Riitta, Ikram, M Arfan, and van den Ende, Joyce

Subjects
Biomedical and Clinical Sciences, Headaches, Bipolar Disorder, Human Genome, Genetics, Mental Health, Pain Research, Migraines, Serious Mental Illness, Chronic Pain, Mental Illness, Neurosciences, Brain Disorders, 2.1 Biological and endogenous factors, Neurological, Adult, Carrier Proteins, Comorbidity, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Migraine Disorders, Nerve Tissue Proteins, Polymorphism, Single Nucleotide, Bipolar disorder, Migraine, NBEA, Neurobeachin, BiGS Consortium, IHG Consortium, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Biomedical and clinical sciences, Health sciences, Psychology
Abstract

BackgroundMigraine is a common comorbidity among individuals with bipolar disorder, but the underlying mechanisms for this co-occurrence are poorly understood. The aim of this study was to investigate the genetic background of bipolar patients with and without migraine.MethodsWe performed a genome-wide association analysis contrasting 460 bipolar migraneurs with 914 bipolar patients without migraine from the Bipolar Genome Study (BiGS).ResultsWe identified one genome-wide significant association between migraine in bipolar disorder patients and rs1160720, an intronic single nucleotide polymorphism (SNP) in the NBEA gene (P=2.97 × 10(-8), OR: 1.82, 95% CI: 1.47-2.25), although this was not replicated in a smaller sample of 289 migraine cases.LimitationsOur study is based on self-reported migraine.ConclusionsNBEA encodes neurobeachin, a scaffolding protein primarily expressed in the brain and involved in trafficking of vesicles containing neurotransmitter receptors. This locus has not previously been implicated in migraine per se. We found no evidence of association in data from the GWAS migraine meta-analysis consortium (n=118,710 participants) suggesting that the association might be specific to migraine co-morbid with bipolar disorder.

Published
2015

13. Hyperexcitable interneurons trigger cortical spreading depression in an Scn1a migraine model

Author

Auffenberg, Eva, Hedrich, Ulrike B.S., Barbieri, Raffaella, Miely, Daniela, Groschup, Bernhard, Wuttke, Thomas V., Vogel, Niklas, Luhrs, Philipp, Zanardi, Ilaria, Bertelli, Sara, Spielmann, Nadine, Gailus-Durner, Valerie, Fuchs, Helmut, de Angelis, Martin Hrabe, Pusch, Michael, Dichgans, Martin, Lerche, Holger, Gavazzo, Paola, Plesnila, Nikolaus, and Freilinger, Tobias

Subjects
Cerebral cortex -- Physiological aspects -- Health aspects, Neural oscillations -- Health aspects -- Genetic aspects, Migraine -- Models -- Genetic aspects -- Physiological aspects, Neural transmission -- Health aspects -- Genetic aspects, Health care industry
Abstract

Cortical spreading depression (CSD), a wave of depolarization followed by depression of cortical activity, is a pathophysiological process implicated in migraine with aura and various other brain pathologies, such as ischemic stroke and traumatic brain injury. To gain insight into the pathophysiology of CSD, we generated a mouse model for a severe monogenic subtype of migraine with aura, familial hemiplegic migraine type 3 (FHM3). FHM3 is caused by mutations in SCN1A, encoding the voltage-gated [Na.sup.+] channel [Na.sub.V]1.1 predominantly expressed in inhibitory interneurons. Homozygous [Scn1a.sup.L1649Q] knock-in mice died prematurely, whereas heterozygous mice had a normal lifespan. Heterozygous [Scn1a.sup.L1649Q] knock-in mice compared with WT mice displayed a significantly enhanced susceptibility to CSD. We found L1649Q to cause a gain-of-function effect with an impaired [Na.sup.+]*-channel inactivation and increased ramp [Na.sup.+] currents leading to hyperactivity of fast-spiking inhibitory interneurons. Brain slice recordings using [K.sup.+]-sensitive electrodes revealed an increase in extracellular [K.sup.+] in the early phase of CSD in heterozygous mice, likely representing the mechanistic link between interneuron hyperactivity and CSD initiation. The neuronal phenotype and premature death of homozygous [Scn1a.sup.L1649Q] knock-in mice was partially rescued by GS967, a blocker of persistent [Na.sup.+] currents. Collectively, our findings identify interneuron hyperactivity as a mechanism to trigger CSD., Introduction With a prevalence of 10% to 15% in the general population, migraine is one of the most common neurological diseases (1, 2) and is rated as one of the [...]

Published
2021
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14. Molecular genetic overlap between migraine and major depressive disorder

Author

Yang, Yuanhao, Zhao, Huiying, Boomsma, Dorret I, Ligthart, Lannie, Belin, Andrea C., Smith, George Davey, Esko, Tonu, Freilinger, Tobias M., Hansen, Thomas Folkmann, Ikram, M. Arfan, Kallela, Mikko, Kubisch, Christian, Paraskevi, Christofidou, Strachan, David P., Wessman, Maija, The International Headache Genetics Consortium, van den Maagdenberg, Arn M. J. M., Terwindt, Gisela M., and Nyholt, Dale R.

Published
2018
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18. Erratum zu: Konsensusstatement der Migräne- und Kopfschmerzgesellschaften (DMKG, ÖKSG & SKG) zur Therapiedauer der medikamentösen Migräneprophylaxe

Author

Goßrau, Gudrun, primary, Förderreuther, Stefanie, additional, Ruscheweyh, Ruth, additional, Ruschil, Victoria, additional, Sprenger, Till, additional, Lewis, David, additional, Kamm, Katharina, additional, Freilinger, Tobias, additional, Neeb, Lars, additional, Malzacher, Volker, additional, Meier, Uwe, additional, Gehring, Klaus, additional, Kraya, Torsten, additional, Dresler, Thomas, additional, Schankin, Christoph J., additional, Gantenbein, Andreas R., additional, Brössner, Gregor, additional, Zebenholzer, Karin, additional, Diener, Hans-Christoph, additional, Gaul, Charly, additional, and Jürgens, Tim P., additional

Published
2023
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19. Genome wide association study identifies variants in NBEA associated with migraine in bipolar disorder

Author

Kelsoe, John R., Greenwood, Tiffany A., Nievergelt, Caroline M., McKinney, Rebecca, Shilling, Paul D., Smith, Erin N., Schork, Nicholas J., Bloss, Cinnamon S., Nurnberger, John I., Jr., Edenberg, Howard J., Foroud, Tatiana, Koller, Daniel L., Gershon, Elliot S., Badner, Judith A., Liu, Chunyu, Scheftner, William A., Lawson, William B., Nwulia, Evaristus A., Hipolito, Maria, Potash, James, Coryell, William, Rice, John, Byerley, William, McMahon, Francis J., Berrettini, Wade H., Zandi, Peter P., Mahon, Pamela B., McInnis, Melvin G., Zöllner, Sebastian, Zhang, Peng, Craig, David W., Szelinger, Szabolics, Barrett, Thomas B., Schulze, Thomas G., Wedenoja, Juho, Kaunisto, Mari A., Heikkilä, Kauko, Kaprio, Jaakko, Wessman, Maija, Kallela, Mikko, Färkkilä, Markus, Artto, Ville, Aromaa, Arpo, Eriksson, Johan G., Winsvold, Bendik S., Zwart, John-Anker, Gormley, Padhraig, Palotie, Aarno, Kurth, Tobias, Rose, Lynda M., Buring, Julie E., Ridker, Paul M., Chasman, Daniel I., Bettella, Francesco, Steinberg, Stacy, Stefansson, Hreinn, Stefansson, Kari, McMahon, George, Davey-Smith, George, Malik, Rainer, Freilinger, Tobias, Erich Wichmann, Heinz, Dichgans, Martin, Muller-Myhsok, Bertram, Meitinger, Thomas, de Vries, Boukje, Terwindt, Gisela, Stam, Anine H., Frants, Rune R., Pelzer, Nadine, Weller, Claudia M., Zielman, Ronald, Ferrari, Michel D., van den Maagdenberg, Arn M.J.M., Medland, Sarah E., Montgomery, Grant W., Martin, Nicholas G., Nyholt, Dale R., Todt, Unda, Borck, Guntram, Kubisch, Christian, Quaye, Lydia, Williams, Frances M.K., Cherkas, Lynn, Koiranen, Markku, Hartikainen, Anna-Liisa, Pouta, Anneli, Jarvelin, Marjo-Riitta, Arfan Ikram, M., van den Ende, Joyce, Uitterlinden, Andre G., Hofman, Albert, Amin, Najaf, van Duijn, Cornelia, Lehtimäki, Terho, Ligthart, Lannie, Hottenga, Jouke-Jan, Vink, Jacqueline M., Penninx, Brenda W., Boomsma, Dorret I., Schürks, Markus, Jakobsson, Finnbogi, Schoenen, Jean, Heath, Andrew C., Madden, Pamela A.F., Göbel, Hartmut, Heinze, Axel, Heinze-Kuhn, Katja, Schreiber, Stefan, Anttila, Verneri, Daly, Mark J., Alexander, Michael, Raitakari, Olli, Strachan, David P., Jacobsen, Kaya K., Zayats, Tetyana, Akiskal, Hagop S., Haavik, Jan, Bernt Fasmer, Ole, Johansson, Stefan, and Oedegaard, Ketil J.

Published
2015
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20. [Untitled]

Author

Goßrau, Gudrun, Förderreuther, Stefanie, Ruscheweyh, Ruth, Ruschil, Victoria, Sprenger, Till, Lewis, David, Kamm, Katharina, Freilinger, Tobias, Neeb, Lars, Malzacher, Volker, Meier, Uwe, Gehring, Klaus, Kraya, Torsten, Dresler, Thomas, Schankin, Christoph J, Gantenbein, Andreas R, Brössner, Gregor, Zebenholzer, Karin, Diener, Hans-Christoph, Gaul, Charly, and Jürgens, Tim P

Subjects
610 Medizin und Gesundheit
Published
2023
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21. [Untitled]

Author

Goßrau, Gudrun, Förderreuther, Stefanie, Ruscheweyh, Ruth, Ruschil, Victoria, Sprenger, Till, Lewis, David, Kamm, Katharina, Freilinger, Tobias, Neeb, Lars, Malzacher, Volker, Meier, Uwe, Gehring, Klaus, Kraya, Torsten, Dresler, Thomas, Schankin, Christoph J, Gantenbein, Andreas R, Brössner, Gregor, Zebenholzer, Karin, Diener, Hans-Christoph, Gaul, Charly, and Jürgens, Tim P

Subjects
610 Medicine & health
Published
2023
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22. Konsensusstatement der Migräne- und Kopfschmerzgesellschaften (DMKG, ÖKSG & SKG) zur Therapiedauer der medikamentösen Migräneprophylaxe

Author

Goßrau, Gudrun, primary, Förderreuther, Stefanie, additional, Ruscheweyh, Ruth, additional, Ruschil, Victoria, additional, Sprenger, Till, additional, Lewis, David, additional, Kamm, Katharina, additional, Freilinger, Tobias, additional, Neeb, Lars, additional, Malzacher, Volker, additional, Meier, Uwe, additional, Gehring, Klaus, additional, Kraya, Torsten, additional, Dresler, Thomas, additional, Schankin, Christoph J., additional, Gantenbein, Andreas R., additional, Brössner, Gregor, additional, Zebenholzer, Karin, additional, Diener, Hans-Christoph, additional, Gaul, Charly, additional, and Jürgens, Tim P., additional

Published
2022
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23. Gene co-expression analysis identifies brain regions and cell types involved in migraine pathophysiology: a GWAS-based study using the Allen Human Brain Atlas

Author

Eising, Else, Huisman, Sjoerd M. H., Mahfouz, Ahmed, Vijfhuizen, Lisanne S., Anttila, Verneri, Winsvold, Bendik S., Kurth, Tobias, Ikram, M. Arfan, Freilinger, Tobias, Kaprio, Jaakko, Boomsma, Dorret I., van Duijn, Cornelia M., Järvelin, Marjo-Riitta R., Zwart, John-Anker, Quaye, Lydia, Strachan, David P., Kubisch, Christian, Dichgans, Martin, Davey Smith, George, Stefansson, Kari, Palotie, Aarno, Chasman, Daniel I., Ferrari, Michel D., Terwindt, Gisela M., de Vries, Boukje, Nyholt, Dale R., Lelieveldt, Boudewijn P. F., van den Maagdenberg, Arn M. J. M., and Reinders, Marcel J. T.

Published
2016
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24. Konsensusstatement der Migräne- und Kopfschmerzgesellschaften (DMKG, ÖKSG & SKG) zur Therapiedauer der medikamentösen Migräneprophylaxe

Author

Goßrau, Gudrun, Förderreuther, Stefanie, Ruscheweyh, Ruth, Ruschil, Victoria, Sprenger, Till, Lewis, David, Kamm, Katharina, Freilinger, Tobias, Neeb, Lars, Malzacher, Volker, Meier, Uwe, Gehring, Klaus, Kraya, Torsten, Dresler, Thomas, Schankin, Christoph J., Gantenbein, Andreas R., Brössner, Gregor, Zebenholzer, Karin, Diener, Hans-Christoph, Gaul, Charly, Jürgens, Tim P., Goßrau, Gudrun, Förderreuther, Stefanie, Ruscheweyh, Ruth, Ruschil, Victoria, Sprenger, Till, Lewis, David, Kamm, Katharina, Freilinger, Tobias, Neeb, Lars, Malzacher, Volker, Meier, Uwe, Gehring, Klaus, Kraya, Torsten, Dresler, Thomas, Schankin, Christoph J., Gantenbein, Andreas R., Brössner, Gregor, Zebenholzer, Karin, Diener, Hans-Christoph, Gaul, Charly, and Jürgens, Tim P.

Abstract

Migräne ist die häufigste neurologische Erkrankung und kann mit einem hohen Grad der Beeinträchtigung einhergehen. Neben nichtmedikamentösen Ansätzen zur Reduktion der Migränefrequenz stehen medikamentöse Migräneprophylaxen zur Verfügung. Zur Indikation und Anwendung liegen evidenzbasierte Leitlinien der Deutschen Migräne- und Kopfschmerzgesellschaft (DMKG) und Deutschen Gesellschaft für Neurologie (DGN), Österreichischen Kopfschmerzgesellschaft (ÖKSG) sowie Schweizer Kopfwehgesellschaft (SKG) vor. Für therapierelevante Fragen wie z. B. der notwendigen und sinnvollen Dauer einer medikamentösen Migräneprophylaxe können aus bisherigen Studiendaten keine Rückschlüsse gezogen werden. Ziel dieser Übersicht ist die Formulierung von Empfehlungen zur Therapiedauer bei wirksamer medikamentöser Migräneprophylaxe, die die aktuelle Datenlage und – bei fehlenden Daten – die Expertenmeinungen berücksichtigen., Migraine is the most common neurological disorder and can be associated with a high degree of disability. In addition to non-pharmacological approaches to reduce migraine frequency, pharmacological migraine preventatives are available. Evidencebased guidelines from the German Migraine and Headache Society (DMKG), and German Society for Neurology (DGN), Austrian Headache Society (ÖKSG), and Swiss Headache Society (SKG) are available for indication and application. For therapyrelevant questions such as the duration of a pharmacological migraine prevention, no conclusions can be drawn from currently available study data. The aim of this review is to present a therapy consensus statement that integrates the current data situation and, where data are lacking, expert opinions. The resulting current recommendations on the duration of therapy for pharmacological migraine prophylaxis are shown here.

Published
2022

26. Additional file 1 of Neurologic manifestations of COVID-19 in critically ill patients: results of the prospective multicenter registry PANDEMIC

Author

Dimitriadis, Konstantinos, Meis, Jan, Neugebauer, Hermann, Barlinn, Kristian, Neumann, Bernhard, Gahn, Georg, Lochner, Piergiorgio, Knier, Benjamin, Lindemann, Sarah, Sühs, Kurt Wolfram, Szabo, Kristina, Pfefferkorn, Thomas, Schirotzek, Ingo, Freilinger, Tobias, Burc, Bassa, Günther, Albrecht, Wittstock, Matthias, Schramm, Patrick, Reimann, Gernot, Godau, Jana, Nagy, Gabor, Koenig, Fatima B., Essig, Fabian, Klinker, Hartwig, Hartmann, Christian, Schmidbauer, Moritz L., Steinberg, Tim, Lefterova, Lora, Klose, Christina, and Bösel, Julian

Abstract

Additional file 1. Additional information on Methods (list of parameters listed in the eCRF, list of categories of disorders and underlying diseases, definitions and statistics. Supplement Table 1: Neurologic past medical history according to disease categories (multiple answers possible). Supplement Table 2: PANDEMIC inclusion criteria and COVID state of disease according to disease categories (multiple answers possible). Supplement Table 3: Neurologic symptoms according to disease categories in 392 patients (multiple answers possible). Supplement Table 4: Diagnostic findings in 392 patients (multiple answers possible). Supplement Table 5: Factors influencing the occurrence of a disease category. Supplement Table 6: Factors influencing the occurrence of most common diseases. Supplement Table 7: Factors influencing the decision to therapy limitation.

Published
2022
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29. Causal relationships between migraine and microstructural white matter: a Mendelian randomization study.

Author

Zhao, Lei, Zhao, Wenhui, International Headache Genetics Consortium (IHGC), Anttila, Verneri, Artto, Ville, Belin, Andrea C., Bjornsdottir, Anna, Bjornsdottir, Gyda, Boomsma, Dorret I., Børte, Sigrid, Chalmer, Mona A., Chasman, Daniel I., Cormand, Bru, Cuenca-Leon, Ester, Davey-Smith, George, de Boer, Irene, Dichgans, Martin, Esko, Tonu, Freilinger, Tobias, and Gormley, Padhraig

Subjects
MIGRAINE risk factors, STATISTICS, WHITE matter (Nerve tissue), RISK assessment, GENOME-wide association studies, DESCRIPTIVE statistics, RESEARCH funding, ODDS ratio, DATA analysis, SENSITIVITY & specificity (Statistics), CAUSALITY (Physics)
Abstract

Background: Migraine is a disabling neurological disorder with the pathophysiology yet to be understood. The microstructural alteration in brain white matter (WM) has been suggested to be related to migraine in recent studies, but these evidence are observational essentially and cannot infer a causal relationship. The present study aims to reveal the causal relationship between migraine and microstructural WM using genetic data and Mendelian randomization (MR). Methods: We collected the Genome-wide association study (GWAS) summary statistics of migraine (48,975 cases / 550,381 controls) and 360 WM imaging-derived phenotypes (IDPs) (31,356 samples) that were used to measure microstructural WM. Based on instrumental variables (IVs) selected from the GWAS summary statistics, we conducted bidirectional two-sample MR analyses to infer bidirectional causal associations between migraine and microstructural WM. In forward MR analysis, we inferred the causal effect of microstructural WM on migraine by reporting the odds ratio (OR) that quantified the risk change of migraine for per 1 standard deviation (SD) increase of IDPs. In reverse MR analysis, we inferred the causal effect of migraine on microstructural WM by reporting the β value that represented SDs of changes in IDPs were caused by migraine. Results: Three WM IDPs showed significant causal associations (p < 3.29 × 10− 4, Bonferroni correction) with migraine and were proved to be reliable via sensitivity analysis. The mode of anisotropy (MO) of left inferior fronto-occipital fasciculus (OR = 1.76, p = 6.46 × 10− 5) and orientation dispersion index (OD) of right posterior thalamic radiation (OR = 0.78, p = 1.86 × 10− 4) exerted significant causal effects on migraine. Migraine exerted a significant causal effect on the OD of left superior cerebellar peduncle (β = − 0.09, p = 2.78 × 10− 4). Conclusions: Our findings provided genetic evidence for the causal relationships between migraine and microstructural WM, bringing new insights into brain structure for the development and experience of migraine. [ABSTRACT FROM AUTHOR]

Published
2023
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31. 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

33. 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

34. Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease

Author

Bryois, Julien, Skene, Nathan G., Hansen, Thomas Folkmann, Kogelman, Lisette J.A., Watson, Hunna J., Liu, Zijing, Adan, Roger, Alfredsson, Lars, Ando, Tetsuya, Andreassen, Ole, Baker, Jessica, Bergen, Andrew, Berrettini, Wade, Birgegård, Andreas, Boden, Joseph, Boehm, Ilka, Boni, Claudette, Boraska Perica, Vesna, Brandt, Harry, Breen, Gerome, Buehren, Katharina, Bulik, Cynthia, Burghardt, Roland, Cassina, Matteo, Cichon, Sven, Clementi, Maurizio, Coleman, Jonathan, Cone, Roger, Courtet, Philippe, Crawford, Steven, Crow, Scott, Crowley, James, Danner, Unna, Davis, Oliver, de Zwaan, Martina, Dedoussis, George, Degortes, Daniela, DeSocio, Janiece, Dick, Danielle, Dikeos, Dimitris, Dina, Christian, Dmitrzak-Weglarz, Monika, Docampo Martinez, Elisa, Duncan, Laramie, Egberts, Karin, Ehrlich, Stefan, Escaramís, Geòrgia, Esko, Tõnu, Estivill, Xavier, Farmer, Anne, Favaro, Angela, Fernández-Aranda, Fernando, Fichter, Manfred, Fischer, Krista, Föcker, Manuel, Foretova, Lenka, Forstner, Andreas, Forzan, Monica, Franklin, Christopher, Gallinger, Steven, Gaspar, Héléna, Giegling, Ina, Giuranna, Johanna, Giusti-Rodríquez, Paola, Gonidakis, Fragiskos, Gordon, Scott, Gorwood, Philip, Gratacos Mayora, Monica, Grove, Jakob, Guillaume, Sébastien, Guo, Yiran, Hakonarson, Hakon, Halmi, Katherine, Hanscombe, Ken, Hatzikotoulas, Konstantinos, Hauser, Joanna, Hebebrand, Johannes, Helder, Sietske, Henders, Anjali, Herms, Stefan, Herpertz-Dahlmann, Beate, Herzog, Wolfgang, Hinney, Anke, Horwood, L. John, Hübel, Christopher, Huckins, Laura, Hudson, James, Imgart, Hartmut, Inoko, Hidetoshi, Janout, Vladimir, Jiménez-Murcia, Susana, Johnson, Craig, Jordan, Jennifer, Julià, Antonio, Juréus, Anders, Kalsi, Gursharan, Kaminská, Deborah, Kaplan, Allan, Kaprio, Jaakko, Karhunen, Leila, Karwautz, Andreas, Kas, Martien, Kaye, Walter, Kennedy, James, Kennedy, Martin, Keski-Rahkonen, Anna, Kiezebrink, Kirsty, Kim, Youl Ri, Kirk, Katherine, Klareskog, Lars, Klump, Kelly, Knudsen, Gun Peggy, La Via, Maria, Landén, Mikael, Larsen, Janne, Le Hellard, Stephanie, Leppä, Virpi, Levitan, Robert, Li, Dong, Lichtenstein, Paul, Lilenfeld, Lisa, Lin, Bochao Danae, Lissowska, Jolanta, Luykx, Jurjen, Magistretti, Pierre, Maj, Mario, Mannik, Katrin, Marsal, Sara, Marshall, Christian, Martin, Nicholas, Mattheisen, Manuel, Mattingsdal, Morten, McDevitt, Sara, McGuffin, Peter, Medland, Sarah, Metspalu, Andres, Meulenbelt, Ingrid, Micali, Nadia, Mitchell, James, Mitchell, Karen, Monteleone, Palmiero, Monteleone, Alessio Maria, Montgomery, Grant, Mortensen, Preben Bo, Munn-Chernoff, Melissa, Nacmias, Benedetta, Navratilova, Marie, Norring, Claes, Ntalla, Ioanna, Olsen, Catherine, Ophoff, Roel, O’Toole, Julie, Padyukov, Leonid, Palotie, Aarno, Pantel, Jacques, Papezova, Hana, Parker, Richard, Pearson, John, Pedersen, Nancy, Petersen, Liselotte, Pinto, Dalila, Purves, Kirstin, Rabionet, Raquel, Raevuori, Anu, Ramoz, Nicolas, Reichborn-Kjennerud, Ted, Ricca, Valdo, Ripatti, Samuli, Ripke, Stephan, Ritschel, Franziska, Roberts, Marion, Rotondo, Alessandro, Rujescu, Dan, Rybakowski, Filip, Santonastaso, Paolo, Scherag, André, Scherer, Stephen, Schmidt, Ulrike, Schork, Nicholas, Schosser, Alexandra, Seitz, Jochen, Slachtova, Lenka, Slagboom, P. Eline, Slof-Op ‘t Landt, Margarita, Slopien, Agnieszka, Sorbi, Sandro, Strober, Michael, Stuber, Garret, Sullivan, Patrick, Świątkowska, Beata, Szatkiewicz, Jin, Tachmazidou, Ioanna, Tenconi, Elena, Thornton, Laura, Tortorella, Alfonso, Tozzi, Federica, Treasure, Janet, Tsitsika, Artemis, Tyszkiewicz-Nwafor, Marta, Tziouvas, Konstantinos, van Elburg, Annemarie, van Furth, Eric, Wade, Tracey, Wagner, Gudrun, Walton, Esther, Watson, Hunna, Werge, Thomas, Whiteman, David, Widen, Elisabeth, Woodside, D. Blake, Yao, Shuyang, Yilmaz, Zeynep, Zeggini, Eleftheria, Zerwas, Stephanie, Zipfel, Stephan, Anttila, Verneri, Artto, Ville, Belin, Andrea Carmine, de Boer, Irene, Boomsma, Dorret I., Børte, Sigrid, Chasman, Daniel I., Cherkas, Lynn, Christensen, Anne Francke, Cormand, Bru, Cuenca-Leon, Ester, Davey-Smith, George, Dichgans, Martin, van Duijn, Cornelia, Esko, Tonu, Esserlind, Ann Louise, Ferrari, Michel, Frants, Rune R., Freilinger, Tobias, Furlotte, Nick, Gormley, Padhraig, Griffiths, Lyn, Hamalainen, Eija, Hiekkala, Marjo, Ikram, M. Arfan, Ingason, Andres, Järvelin, Marjo Riitta, Kajanne, Risto, Maagdenberg, Arn van den, Nyholt, Dale R., Zhao, Huiying, Bell, Robert, Wilson, Catherine, other, and, Bryois, Julien, Skene, Nathan G., Hansen, Thomas Folkmann, Kogelman, Lisette J.A., Watson, Hunna J., Liu, Zijing, Adan, Roger, Alfredsson, Lars, Ando, Tetsuya, Andreassen, Ole, Baker, Jessica, Bergen, Andrew, Berrettini, Wade, Birgegård, Andreas, Boden, Joseph, Boehm, Ilka, Boni, Claudette, Boraska Perica, Vesna, Brandt, Harry, Breen, Gerome, Buehren, Katharina, Bulik, Cynthia, Burghardt, Roland, Cassina, Matteo, Cichon, Sven, Clementi, Maurizio, Coleman, Jonathan, Cone, Roger, Courtet, Philippe, Crawford, Steven, Crow, Scott, Crowley, James, Danner, Unna, Davis, Oliver, de Zwaan, Martina, Dedoussis, George, Degortes, Daniela, DeSocio, Janiece, Dick, Danielle, Dikeos, Dimitris, Dina, Christian, Dmitrzak-Weglarz, Monika, Docampo Martinez, Elisa, Duncan, Laramie, Egberts, Karin, Ehrlich, Stefan, Escaramís, Geòrgia, Esko, Tõnu, Estivill, Xavier, Farmer, Anne, Favaro, Angela, Fernández-Aranda, Fernando, Fichter, Manfred, Fischer, Krista, Föcker, Manuel, Foretova, Lenka, Forstner, Andreas, Forzan, Monica, Franklin, Christopher, Gallinger, Steven, Gaspar, Héléna, Giegling, Ina, Giuranna, Johanna, Giusti-Rodríquez, Paola, Gonidakis, Fragiskos, Gordon, Scott, Gorwood, Philip, Gratacos Mayora, Monica, Grove, Jakob, Guillaume, Sébastien, Guo, Yiran, Hakonarson, Hakon, Halmi, Katherine, Hanscombe, Ken, Hatzikotoulas, Konstantinos, Hauser, Joanna, Hebebrand, Johannes, Helder, Sietske, Henders, Anjali, Herms, Stefan, Herpertz-Dahlmann, Beate, Herzog, Wolfgang, Hinney, Anke, Horwood, L. John, Hübel, Christopher, Huckins, Laura, Hudson, James, Imgart, Hartmut, Inoko, Hidetoshi, Janout, Vladimir, Jiménez-Murcia, Susana, Johnson, Craig, Jordan, Jennifer, Julià, Antonio, Juréus, Anders, Kalsi, Gursharan, Kaminská, Deborah, Kaplan, Allan, Kaprio, Jaakko, Karhunen, Leila, Karwautz, Andreas, Kas, Martien, Kaye, Walter, Kennedy, James, Kennedy, Martin, Keski-Rahkonen, Anna, Kiezebrink, Kirsty, Kim, Youl Ri, Kirk, Katherine, Klareskog, Lars, Klump, Kelly, Knudsen, Gun Peggy, La Via, Maria, Landén, Mikael, Larsen, Janne, Le Hellard, Stephanie, Leppä, Virpi, Levitan, Robert, Li, Dong, Lichtenstein, Paul, Lilenfeld, Lisa, Lin, Bochao Danae, Lissowska, Jolanta, Luykx, Jurjen, Magistretti, Pierre, Maj, Mario, Mannik, Katrin, Marsal, Sara, Marshall, Christian, Martin, Nicholas, Mattheisen, Manuel, Mattingsdal, Morten, McDevitt, Sara, McGuffin, Peter, Medland, Sarah, Metspalu, Andres, Meulenbelt, Ingrid, Micali, Nadia, Mitchell, James, Mitchell, Karen, Monteleone, Palmiero, Monteleone, Alessio Maria, Montgomery, Grant, Mortensen, Preben Bo, Munn-Chernoff, Melissa, Nacmias, Benedetta, Navratilova, Marie, Norring, Claes, Ntalla, Ioanna, Olsen, Catherine, Ophoff, Roel, O’Toole, Julie, Padyukov, Leonid, Palotie, Aarno, Pantel, Jacques, Papezova, Hana, Parker, Richard, Pearson, John, Pedersen, Nancy, Petersen, Liselotte, Pinto, Dalila, Purves, Kirstin, Rabionet, Raquel, Raevuori, Anu, Ramoz, Nicolas, Reichborn-Kjennerud, Ted, Ricca, Valdo, Ripatti, Samuli, Ripke, Stephan, Ritschel, Franziska, Roberts, Marion, Rotondo, Alessandro, Rujescu, Dan, Rybakowski, Filip, Santonastaso, Paolo, Scherag, André, Scherer, Stephen, Schmidt, Ulrike, Schork, Nicholas, Schosser, Alexandra, Seitz, Jochen, Slachtova, Lenka, Slagboom, P. Eline, Slof-Op ‘t Landt, Margarita, Slopien, Agnieszka, Sorbi, Sandro, Strober, Michael, Stuber, Garret, Sullivan, Patrick, Świątkowska, Beata, Szatkiewicz, Jin, Tachmazidou, Ioanna, Tenconi, Elena, Thornton, Laura, Tortorella, Alfonso, Tozzi, Federica, Treasure, Janet, Tsitsika, Artemis, Tyszkiewicz-Nwafor, Marta, Tziouvas, Konstantinos, van Elburg, Annemarie, van Furth, Eric, Wade, Tracey, Wagner, Gudrun, Walton, Esther, Watson, Hunna, Werge, Thomas, Whiteman, David, Widen, Elisabeth, Woodside, D. Blake, Yao, Shuyang, Yilmaz, Zeynep, Zeggini, Eleftheria, Zerwas, Stephanie, Zipfel, Stephan, Anttila, Verneri, Artto, Ville, Belin, Andrea Carmine, de Boer, Irene, Boomsma, Dorret I., Børte, Sigrid, Chasman, Daniel I., Cherkas, Lynn, Christensen, Anne Francke, Cormand, Bru, Cuenca-Leon, Ester, Davey-Smith, George, Dichgans, Martin, van Duijn, Cornelia, Esko, Tonu, Esserlind, Ann Louise, Ferrari, Michel, Frants, Rune R., Freilinger, Tobias, Furlotte, Nick, Gormley, Padhraig, Griffiths, Lyn, Hamalainen, Eija, Hiekkala, Marjo, Ikram, M. Arfan, Ingason, Andres, Järvelin, Marjo Riitta, Kajanne, Risto, Maagdenberg, Arn van den, Nyholt, Dale R., Zhao, Huiying, Bell, Robert, Wilson, Catherine, and other, and

Abstract

Genome-wide association studies have discovered hundreds of loci associated with complex brain disorders, but it remains unclear in which cell types these loci are active. Here we integrate genome-wide association study results with single-cell transcriptomic data from the entire mouse nervous system to systematically identify cell types underlying brain complex traits. We show that psychiatric disorders are predominantly associated with projecting excitatory and inhibitory neurons. Neurological diseases were associated with different cell types, which is consistent with other lines of evidence. Notably, Parkinson’s disease was genetically associated not only with cholinergic and monoaminergic neurons (which include dopaminergic neurons) but also with enteric neurons and oligodendrocytes. Using post-mortem brain transcriptomic data, we confirmed alterations in these cells, even at the earliest stages of disease progression. Our study provides an important framework for understanding the cellular basis of complex brain maladies, and reveals an unexpected role of oligodendrocytes in Parkinson’s disease.

Published
2020

37. Mutation in the neuronal voltage-gated sodium channel SCN1A in familial hemiplegic migraine

Author

Dichgans, Martin, Freilinger, Tobias, Eckstein, Gertrud, Babini, Elena, Lorenz-Depiereux, Bettina, Biskup, Saskia, Ferrari, Michel D., Herzog, Jurgen, van den Maagdenberg, Arn M.J.M., Pusch, Michael, and Strom, Tim M.

Subjects
Sodium channels -- Research, Migraine -- Diagnosis, Migraine -- Risk factors, Migraine -- Care and treatment
Published
2005

42. A high-density association screen of 155 ion transport genes for involvement with common migraine

Author

Nyholt, Dale R., LaForge, K. Steven, Kallela, Mikko, Alakurtti, Kirsi, Anttila, Verneri, Färkkilä, Markus, Hämaläinen, Eija, Kaprio, Jaakko, Kaunisto, Mari A., Heath, Andrew C., Montgomery, Grant W., Göbel, Hartmut, Todt, Unda, Ferrari, Michel D., Launer, Lenore J., Frants, Rune R., Terwindt, Gisela M., de Vries, Boukje, Verschuren, W.M. Monique, Brand, Jan, Freilinger, Tobias, Pfaffenrath, Volker, Straube, Andreas, Ballinger, Dennis G., Zhan, Yiping, Daly, Mark J., Cox, David R., Dichgans, Martin, van den Maagdenberg, Arn M.J.M., Kubisch, Christian, Martin, Nicholas G., Wessman, Maija, Peltonen, Leena, and Palotie, Aarno

Published
2008

46. Migraine polygenic risk score associates with efficacy of migraine-specific drugs

Author

Kogelman, Lisette J. A., Esserlind, Ann-Louise, Christensen, Anne Francke, Awasthi, Swapnil, Ripke, Stephan, Ingason, Andres, Davidsson, Olafur B., Erikstrup, Christian, Hjalgrim, Henrik, Ullum, Henrik, Olesen, Jes, Hansen, Thomas Folkmann, Gudbjartsson, Daniel, Gastafsson, Omar, Stefansson, Kari, Stefansson, Hreinn, Porsteinsdottir, Unnur, Andersen, Steffen, Banasik, Karina, Brunak, Søren, Buil, Alfonso, Burgdorf, Kristoffer, Gregor, Jemec, Jennum, Poul, Nielsen, Kasper Rene, Nyegaard, Mette, Paarup, Helene Mariana, Pedersen, Ole Birger, Sørensen, Erik, Werge, Thomas, Anttila, Verneri, Artto, Ville, Belin, Andrea Carmine, de Boer, Irene, Boomsma, Dorret, I, Borte, Sigrid, Chasman, Daniel, I, Cherkas, Lynn, Cormand, Bru, Cuenca-Leon, Ester, Davey-Smith, George, Dichgans, Martin, van Duijn, Cornelia, Esko, Tonu, Ferrari, Michel, Frants, Rune R., Freilinger, Tobias, Furlotte, Nick, Gormley, Padhraig, Griffiths, Lyn, Hamalainen, Eija, Hiekkala, Marjo, Ikram, M. Arfan, Jarvelin, Marjo-Riitta, Kajanne, Risto, Kallela, Mikko, Kaprio, Jaakko, Kaunisto, Mari, Kubisch, Christian, Kurki, Mitja, Kurth, Tobias, Launer, Lenore, Lehtimaki, Terho, Lessel, Davor, Ligthart, Lannie, Litterman, Nadia, van den Maagdenberg, Arn, Macaya, Alfons, Malik, Rainer, Mangino, Massimo, McMahon, George, Muller-Myhsok, Bertram, Neale, Benjamin M., Northover, Carrie, Nyholt, Dale R., Palotie, Aarno, Palta, Priit, Pedersen, Linda, Pedersen, Nancy, Posthuma, Danielle, Pozo-Rosich, Patricia, Pressman, Alice, Raitakari, Olli, Schurks, Markus, Sintas, Celia, Steinberg, Stacy, Strachan, David, Terwindt, Gisela, Vila-Pueyo, Marta, Wessman, Maija, Winsvold, Bendik S., Zhao, Huiying, Zwart, John-Anker, Kogelman, Lisette J. A., Esserlind, Ann-Louise, Christensen, Anne Francke, Awasthi, Swapnil, Ripke, Stephan, Ingason, Andres, Davidsson, Olafur B., Erikstrup, Christian, Hjalgrim, Henrik, Ullum, Henrik, Olesen, Jes, Hansen, Thomas Folkmann, Gudbjartsson, Daniel, Gastafsson, Omar, Stefansson, Kari, Stefansson, Hreinn, Porsteinsdottir, Unnur, Andersen, Steffen, Banasik, Karina, Brunak, Søren, Buil, Alfonso, Burgdorf, Kristoffer, Gregor, Jemec, Jennum, Poul, Nielsen, Kasper Rene, Nyegaard, Mette, Paarup, Helene Mariana, Pedersen, Ole Birger, Sørensen, Erik, Werge, Thomas, Anttila, Verneri, Artto, Ville, Belin, Andrea Carmine, de Boer, Irene, Boomsma, Dorret, I, Borte, Sigrid, Chasman, Daniel, I, Cherkas, Lynn, Cormand, Bru, Cuenca-Leon, Ester, Davey-Smith, George, Dichgans, Martin, van Duijn, Cornelia, Esko, Tonu, Ferrari, Michel, Frants, Rune R., Freilinger, Tobias, Furlotte, Nick, Gormley, Padhraig, Griffiths, Lyn, Hamalainen, Eija, Hiekkala, Marjo, Ikram, M. Arfan, Jarvelin, Marjo-Riitta, Kajanne, Risto, Kallela, Mikko, Kaprio, Jaakko, Kaunisto, Mari, Kubisch, Christian, Kurki, Mitja, Kurth, Tobias, Launer, Lenore, Lehtimaki, Terho, Lessel, Davor, Ligthart, Lannie, Litterman, Nadia, van den Maagdenberg, Arn, Macaya, Alfons, Malik, Rainer, Mangino, Massimo, McMahon, George, Muller-Myhsok, Bertram, Neale, Benjamin M., Northover, Carrie, Nyholt, Dale R., Palotie, Aarno, Palta, Priit, Pedersen, Linda, Pedersen, Nancy, Posthuma, Danielle, Pozo-Rosich, Patricia, Pressman, Alice, Raitakari, Olli, Schurks, Markus, Sintas, Celia, Steinberg, Stacy, Strachan, David, Terwindt, Gisela, Vila-Pueyo, Marta, Wessman, Maija, Winsvold, Bendik S., Zhao, Huiying, and Zwart, John-Anker

Published
2019

48. Analysis of shared heritability in common disorders of the brain

Author

Brainstorm Consortium, Anttila, Verneri, Bulik-Sullivan, Brendan, Finucane, Hilary K, Walters, Raymond K, Bras, Jose, Duncan, Laramie, Escott-Price, Valentina, Falcone, Guido J, Gormley, Padhraig, Malik, Rainer, Patsopoulos, Nikolaos A, Ripke, Stephan, Wei, Zhi, Yu, Dongmei, Lee, Phil H, Turley, Patrick, Grenier-Boley, Benjamin, Chouraki, Vincent, Kamatani, Yoichiro, Berr, Claudine, Letenneur, Luc, Hannequin, Didier, Amouyel, Philippe, Boland, Anne, Deleuze, Jean-François, Duron, Emmanuelle, Vardarajan, Badri N, Reitz, Christiane, Goate, Alison M, Huentelman, Matthew J, Kamboh, M Ilyas, Larson, Eric B, Rogaeva, Ekaterina, St George-Hyslop, Peter, Hakonarson, Hakon, Kukull, Walter A, Farrer, Lindsay A, Barnes, Lisa L, Beach, Thomas G, Demirci, F Yesim, Head, Elizabeth, Hulette, Christine M, Jicha, Gregory A, Kauwe, John SK, Kaye, Jeffrey A, Leverenz, James B, Levey, Allan I, Lieberman, Andrew P, Pankratz, Vernon S, Poon, Wayne W, Quinn, Joseph F, Saykin, Andrew J, Schneider, Lon S, Smith, Amanda G, Sonnen, Joshua A, Stern, Robert A, Van Deerlin, Vivianna M, Van Eldik, Linda J, Harold, Denise, Russo, Giancarlo, Rubinsztein, David C, Bayer, Anthony, Tsolaki, Magda, Proitsi, Petra, Fox, Nick C, Hampel, Harald, Owen, Michael J, Mead, Simon, Passmore, Peter, Morgan, Kevin, Nöthen, Markus M, Rossor, Martin, Lupton, Michelle K, Hoffmann, Per, Kornhuber, Johannes, Lawlor, Brian, McQuillin, Andrew, Al-Chalabi, Ammar, Bis, Joshua C, Ruiz, Agustin, Boada, Mercè, Seshadri, Sudha, Beiser, Alexa, Rice, Kenneth, Van Der Lee, Sven J, De Jager, Philip L, Geschwind, Daniel H, Riemenschneider, Matthias, Riedel-Heller, Steffi, Rotter, Jerome I, Ransmayr, Gerhard, Hyman, Bradley T, Cruchaga, Carlos, Alegret, Montserrat, Winsvold, Bendik, Palta, Priit, Farh, Kai-How, Cuenca-Leon, Ester, Furlotte, Nicholas, Kurth, Tobias, Ligthart, Lannie, Terwindt, Gisela M, Freilinger, Tobias, Ran, Caroline, Gordon, Scott D, Borck, Guntram, Adams, Hieab HH, Lehtimäki, Terho, Wedenoja, Juho, Buring, Julie E, Schürks, Markus, Hrafnsdottir, Maria, Hottenga, Jouke-Jan, Penninx, Brenda, Artto, Ville, Kaunisto, Mari, Vepsäläinen, Salli, Martin, Nicholas G, Montgomery, Grant W, Kurki, Mitja I, Hämäläinen, Eija, Huang, Hailiang, Huang, Jie, Sandor, Cynthia, Webber, Caleb, Muller-Myhsok, Bertram, Schreiber, Stefan, Salomaa, Veikko, Loehrer, Elizabeth, Göbel, Hartmut, Macaya, Alfons, Pozo-Rosich, Patricia, Hansen, Thomas, Werge, Thomas, Kaprio, Jaakko, Metspalu, Andres, Kubisch, Christian, Ferrari, Michel D, Belin, Andrea C, Van Den Maagdenberg, Arn MJM, Zwart, John-Anker, Boomsma, Dorret, Eriksson, Nicholas, Olesen, Jes, Chasman, Daniel I, Nyholt, Dale R, Avbersek, Andreja, Baum, Larry, Berkovic, Samuel, Bradfield, Jonathan, Buono, Russell J, Catarino, Claudia B, Cossette, Patrick, De Jonghe, Peter, Depondt, Chantal, Dlugos, Dennis, Ferraro, Thomas N, French, Jacqueline, Hjalgrim, Helle, Jamnadas-Khoda, Jennifer, Kälviäinen, Reetta, Kunz, Wolfram S, Lerche, Holger, Leu, Costin, Lindhout, Dick, Lo, Warren, Lowenstein, Daniel, McCormack, Mark, Møller, Rikke S, Molloy, Anne, Ng, Ping-Wing, Oliver, Karen, Privitera, Michael, Radtke, Rodney, Ruppert, Ann-Kathrin, Sander, Thomas, Schachter, Steven, Schankin, Christoph, Scheffer, Ingrid, Schoch, Susanne, Sisodiya, Sanjay M, Smith, Philip, Sperling, Michael, Striano, Pasquale, Surges, Rainer, Thomas, G Neil, Visscher, Frank, Whelan, Christopher D, Zara, Federico, Heinzen, Erin L, Marson, Anthony, Becker, Felicitas, Stroink, Hans, Zimprich, Fritz, Gasser, Thomas, Gibbs, Raphael, Heutink, Peter, Martinez, Maria, Morris, Huw R, Sharma, Manu, Ryten, Mina, Mok, Kin Y, Pulit, Sara, Bevan, Steve, Holliday, Elizabeth, Attia, John, Battey, Thomas, Boncoraglio, Giorgio, Thijs, Vincent, Chen, Wei-Min, Mitchell, Braxton, Rothwell, Peter, Sharma, Pankaj, Sudlow, Cathie, Vicente, Astrid, Markus, Hugh, Kourkoulis, Christina, Pera, Joana, Raffeld, Miriam, Silliman, Scott, Boraska Perica, Vesna, Thornton, Laura M, Huckins, Laura M, William Rayner, N, Lewis, Cathryn M, Gratacos, Monica, Rybakowski, Filip, Keski-Rahkonen, Anna, Raevuori, Anu, Hudson, James I, Reichborn-Kjennerud, Ted, Monteleone, Palmiero, Karwautz, Andreas, Mannik, Katrin, Baker, Jessica H, O'Toole, Julie K, Trace, Sara E, Davis, Oliver SP, Helder, Sietske G, Ehrlich, Stefan, Herpertz-Dahlmann, Beate, Danner, Unna N, Van Elburg, Annemarie A, Clementi, Maurizio, Forzan, Monica, Docampo, Elisa, Lissowska, Jolanta, Hauser, Joanna, Tortorella, Alfonso, Maj, Mario, Gonidakis, Fragiskos, Tziouvas, Konstantinos, Papezova, Hana, Yilmaz, Zeynep, Wagner, Gudrun, Cohen-Woods, Sarah, Herms, Stefan, Julià, Antonio, Rabionet, Raquel, Dick, Danielle M, Ripatti, Samuli, Andreassen, Ole A, Espeseth, Thomas, Lundervold, Astri J, Steen, Vidar M, Pinto, Dalila, Scherer, Stephen W, Aschauer, Harald, Schosser, Alexandra, Alfredsson, Lars, Padyukov, Leonid, Halmi, Katherine A, Mitchell, James, Strober, Michael, Bergen, Andrew W, Kaye, Walter, Szatkiewicz, Jin Peng, Cormand, Bru, Ramos-Quiroga, Josep Antoni, Sánchez-Mora, Cristina, Ribasés, Marta, Casas, Miguel, Hervas, Amaia, Arranz, Maria Jesús, Haavik, Jan, Zayats, Tetyana, Johansson, Stefan, Williams, Nigel, Dempfle, Astrid, Rothenberger, Aribert, Kuntsi, Jonna, Oades, Robert D, Banaschewski, Tobias, Franke, Barbara, Buitelaar, Jan K, Arias Vasquez, Alejandro, Doyle, Alysa E, Reif, Andreas, Lesch, Klaus-Peter, Freitag, Christine, Rivero, Olga, Palmason, Haukur, Romanos, Marcel, Langley, Kate, Rietschel, Marcella, Witt, Stephanie H, Dalsgaard, Soeren, Børglum, Anders D, Waldman, Irwin, Wilmot, Beth, Molly, Nikolas, Bau, Claiton HD, Crosbie, Jennifer, Schachar, Russell, Loo, Sandra K, McGough, James J, Grevet, Eugenio H, Medland, Sarah E, Robinson, Elise, Weiss, Lauren A, Bacchelli, Elena, Bailey, Anthony, Bal, Vanessa, Battaglia, Agatino, Betancur, Catalina, Bolton, Patrick, Cantor, Rita, Celestino-Soper, Patrícia, Dawson, Geraldine, De Rubeis, Silvia, Duque, Frederico, Green, Andrew, Klauck, Sabine M, Leboyer, Marion, Levitt, Pat, Maestrini, Elena, Mane, Shrikant, De-Luca, Daniel Moreno, Parr, Jeremy, Regan, Regina, Reichenberg, Abraham, Sandin, Sven, Vorstman, Jacob, Wassink, Thomas, Wijsman, Ellen, Cook, Edwin, Santangelo, Susan, Delorme, Richard, Rogé, Bernadette, Magalhaes, Tiago, Arking, Dan, Schulze, Thomas G, Thompson, Robert C, Strohmaier, Jana, Matthews, Keith, Melle, Ingrid, Morris, Derek, Blackwood, Douglas, McIntosh, Andrew, Bergen, Sarah E, Schalling, Martin, Jamain, Stéphane, Maaser, Anna, Fischer, Sascha B, Reinbold, Céline S, Fullerton, Janice M, Guzman-Parra, José, Mayoral, Fermin, Schofield, Peter R, Cichon, Sven, Mühleisen, Thomas W, Degenhardt, Franziska, Schumacher, Johannes, Bauer, Michael, Mitchell, Philip B, Gershon, Elliot S, Rice, John, Potash, James B, Zandi, Peter P, Craddock, Nick, Ferrier, I Nicol, Alda, Martin, Rouleau, Guy A, Turecki, Gustavo, Ophoff, Roel, Pato, Carlos, Anjorin, Adebayo, Stahl, Eli, Leber, Markus, Czerski, Piotr M, Cruceanu, Cristiana, Jones, Ian R, Posthuma, Danielle, Andlauer, Till FM, Forstner, Andreas J, Streit, Fabian, Baune, Bernhard T, Air, Tracy, Sinnamon, Grant, Wray, Naomi R, MacIntyre, Donald J, Porteous, David, Homuth, Georg, Rivera, Margarita, Grove, Jakob, Middeldorp, Christel M, Hickie, Ian, Pergadia, Michele, Mehta, Divya, Smit, Johannes H, Jansen, Rick, De Geus, Eco, Dunn, Erin, Li, Qingqin S, Nauck, Matthias, Schoevers, Robert A, Beekman, Aartjan Tf, Knowles, James A, Viktorin, Alexander, Arnold, Paul, Barr, Cathy L, Bedoya-Berrio, Gabriel, Bienvenu, O Joseph, Brentani, Helena, Burton, Christie, Camarena, Beatriz, Cappi, Carolina, Cath, Danielle, Cavallini, Maria, Cusi, Daniele, Darrow, Sabrina, Denys, Damiaan, Derks, Eske M, Dietrich, Andrea, Fernandez, Thomas, Figee, Martijn, Freimer, Nelson, Gerber, Gloria, Grados, Marco, Greenberg, Erica, Hanna, Gregory L, Hartmann, Andreas, Hirschtritt, Matthew E, Hoekstra, Pieter J, Huang, Alden, Huyser, Chaim, Illmann, Cornelia, Jenike, Michael, Kuperman, Samuel, Leventhal, Bennett, Lochner, Christine, Lyon, Gholson J, Macciardi, Fabio, Madruga-Garrido, Marcos, Malaty, Irene A, Maras, Athanasios, McGrath, Lauren, Miguel, Eurípedes C, Mir, Pablo, Nestadt, Gerald, Nicolini, Humberto, Okun, Michael S, Pakstis, Andrew, Paschou, Peristera, Piacentini, John, Pittenger, Christopher, Plessen, Kerstin, Ramensky, Vasily, Ramos, Eliana M, Reus, Victor, Richter, Margaret A, Riddle, Mark A, Robertson, Mary M, Roessner, Veit, Rosário, Maria, Samuels, Jack F, Sandor, Paul, Stein, Dan J, Tsetsos, Fotis, Van Nieuwerburgh, Filip, Weatherall, Sarah, Wendland, Jens R, Wolanczyk, Tomasz, Worbe, Yulia, Zai, Gwyneth, Goes, Fernando S, McLaughlin, Nicole, Nestadt, Paul S, Grabe, Hans-Jorgen, Depienne, Christel, Konkashbaev, Anuar, Lanzagorta, Nuria, Valencia-Duarte, Ana, Bramon, Elvira, Buccola, Nancy, Cahn, Wiepke, Cairns, Murray, Chong, Siow A, Cohen, David, Crespo-Facorro, Benedicto, Crowley, James, Davidson, Michael, DeLisi, Lynn, Dinan, Timothy, Donohoe, Gary, Drapeau, Elodie, Duan, Jubao, Haan, Lieuwe, Hougaard, David, Karachanak-Yankova, Sena, Khrunin, Andrey, Klovins, Janis, Kučinskas, Vaidutis, Lee Chee Keong, Jimmy, Limborska, Svetlana, Loughland, Carmel, Lönnqvist, Jouko, Maher, Brion, Mattheisen, Manuel, McDonald, Colm, Murphy, Kieran C, Nenadic, Igor, Van Os, Jim, Pantelis, Christos, Pato, Michele, Petryshen, Tracey, Quested, Digby, Roussos, Panos, Sanders, Alan R, Schall, Ulrich, Schwab, Sibylle G, Sim, Kang, So, Hon-Cheong, Stögmann, Elisabeth, Subramaniam, Mythily, Toncheva, Draga, Waddington, John, Walters, James, Weiser, Mark, Cheng, Wei, Cloninger, Robert, Curtis, David, Gejman, Pablo V, Henskens, Frans, Mattingsdal, Morten, Oh, Sang-Yun, Scott, Rodney, Webb, Bradley, Breen, Gerome, Churchhouse, Claire, Bulik, Cynthia M, Daly, Mark, Dichgans, Martin, Faraone, Stephen V, Guerreiro, Rita, Holmans, Peter, Kendler, Kenneth S, Koeleman, Bobby, Mathews, Carol A, Price, Alkes, Scharf, Jeremiah, Sklar, Pamela, Williams, Julie, Wood, Nicholas W, Cotsapas, Chris, Palotie, Aarno, Smoller, Jordan W, Sullivan, Patrick, Rosand, Jonathan, Corvin, Aiden, Neale, Benjamin M, Schott, Jonathan M, Anney, Richard, Elia, Josephine, Grigoroiu-Serbanescu, Maria, Edenberg, Howard J, Murray, Robin, Massachusetts General Hospital [Boston], Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], UK Dementia Research Institute (UK DRI), University College of London [London] (UCL), School of Psychology [Cardiff University], Cardiff University, Institute for Stroke and Dementia Research (ISD), Klinikum der Universität [München]-Ludwig Maximilian University [Munich] (LMU), New Jersey Institute of Technology [Newark] (NJIT), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Laboratoire de Biotechnologie et Microbiologie Appliquée (LBMA), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA), 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), Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Gériatrie générale et aigüe [Paris], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Columbia University [New York], Dpt of Neuroscience [New York], Icahn School of Medicine at Mount Sinai [New York] (MSSM), University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), University of Washington [Seattle], Tanz Center Research in Neurodegenerative Diseases [Toronto], University of Toronto, Children’s Hospital of Philadelphia (CHOP ), University of Kentucky (UK), School of medicine, Duke University [Durham], College of medicine, Brigham Young University (BYU), Oregon Health and Science University [Portland] (OHSU), Cleveland Clinic, Department of Neurology, Emory University [Atlanta, GA], Medical School, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Health sciences center, The University of New Mexico [Albuquerque], Institute for Memory Impairments and Neurological Disorders [Irvine], University of California [Irvine] (UC Irvine), University of California (UC)-University of California (UC), Indiana University - Purdue University Indianapolis (IUPUI), Indiana University System, Keck School of Medicine [Los Angeles], University of Southern California (USC), University of South Florida [Tampa] (USF), University of Utah School of Medicine [Salt Lake City], Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Perelman School of Medicine, University of Pennsylvania, Dublin City University [Dublin] (DCU), Functional Genomics Center Zurich, Universität Zürich [Zürich] = University of Zurich (UZH)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Cambridge Institute for Medical Research (CIMR), University of Cambridge [UK] (CAM), Aristotle University of Thessaloniki, Maurice Wohl Clinical Neuroscience Institut, King‘s College London, Dementia Research Centre [London] (DRC), Groupe de recherche clinique Alzheimer Precision Medicine (GRC 21 - APM), Sorbonne Université (SU), MRC Centre for Neuropsychiatric Genetics and Genomics, Medical Research Council-Cardiff University, MRC Prion Unit [London], Queen's University [Belfast] (QUB), School of Life Sciences, University of Nottingham, UK (UON), Rheinische Friedrich-Wilhelms-Universität Bonn, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), QIMR Berghofer Medical Research Institute, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), School of Medicine [Dublin], Trinity College Dublin, Department of Medicine, University of Texas Health Science Center, The University of Texas Health Science Center at Houston (UTHealth), School of Public Health [Boston], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Columbia University Medical Center (CUMC), David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), Saarland University [Saarbrücken], Universität Leipzig, School of Medicine [Los Angeles], Johannes Kepler Universität Linz - Johannes Kepler University Linz [Autriche] (JKU), Department of Neurology [Boston], Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], School of Medecine, Washington University in Saint Louis (WUSTL), Oslo University Hospital [Oslo], Institute for Molecular Medicine Finland [Helsinki] (FIMM), Helsinki Institute of Life Science (HiLIFE), Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, 23andMe Inc., Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Biological Psychology [Amsterdam], Vrije Universiteit Amsterdam [Amsterdam] (VU), Leiden University Medical Center (LUMC), Universiteit Leiden, University-Hospital Munich-Großhadern [München], Karolinska Institutet [Stockholm], Universität Ulm - Ulm University [Ulm, Allemagne], Faculty of Medicine and Life Sciences [Tampere], University of Tampere [Finland], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Landspitali National University Hospital of Iceland, VU University Medical Center [Amsterdam], Boston VA Research Institute (BVARI), Department of Physiology, Anatomy and Genetics [Oxford], University of Oxford, Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, Christian-Albrechts-Universität zu Kiel (CAU), Institute of Clinical Molecular Biology, Kiel University, National Institute for Health and Welfare [Helsinki], Harvard T.H. Chan School of Public Health, Universitat Autònoma de Barcelona (UAB), Vall d'Hebron University Hospital [Barcelona], University of Tartu, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Center for Human and Clinical Genetics, Universiteit Leiden-Universiteit Leiden, University of Copenhagen = Københavns Universitet (UCPH), Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology [Brisbane] (QUT), Discipline of Psychiatry [Dublin], Trinity College Dublin-Trinity College Dublin, Institute of Neurology [London], The University of Hong Kong (HKU), University of Melbourne, Cooper Medical School of Rowan University [Camden] (CMSRU), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), University of Antwerp (UA), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), University of Eastern Finland, Universitätsklinikum Bonn (UKB), Hertie Institute for Clinical Brain Research [Tubingen], University of Tübingen, NIHR Biomedical Research Centre [London], Guy's and St Thomas' NHS Foundation Trust-King‘s College London, University Medical Center [Utrecht], Ohio State University [Columbus] (OSU), University of California [San Francisco] (UC San Francisco), University of California (UC), Royal College of Surgeons in Ireland (RCSI), University of Southern Denmark (SDU), United Christian Hospital [Hong Kong] (UCH), University of Cincinnati (UC), University of Cologne, Inselspital Bern, University of Wales, Jefferson University Hospitals, University of Liverpool, Medizinische Universität Wien = Medical University of Vienna, National Institutes of Health [Bethesda] (NIH), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Institut de Recherche en Santé Digestive (IRSD ), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Lincoln, University of Newcastle [Callaghan, Australia] (UoN), Fondazione IRCCS Istituto Neurologico 'Carlo Besta', University of Virginia, University of Maryland [Baltimore County] (UMBC), University of Maryland System, Royal Holloway [University of London] (RHUL), University of Edinburgh, Universidade de Lisboa = University of Lisbon (ULISBOA), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), University of Split, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Center for Genomic Regulation (CRG-UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), McLean Hospital [Belmont, Ma.], Norwegian Institute of Public Health [Oslo] (NIPH), Università degli Studi di Salerno = University of Salerno (UNISA), University of Bristol [Bristol], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Utrecht University [Utrecht], Azienda Ospedaliera di Padova, Université de Liège, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), Università degli Studi di Perugia = University of Perugia (UNIPG), Università degli studi della Campania 'Luigi Vanvitelli' = University of the Study of Campania Luigi Vanvitelli, National and Kapodistrian University of Athens (NKUA), Charles University [Prague] (CU), SURFACES, Institut de recherches sur la catalyse et l'environnement de Lyon (IRCELYON), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Flinders University [Adelaide, Australia], Virginia Commonwealth University (VCU), University of Oslo (UiO), University of Bergen (UiB), Weill Medical College of Cornell University [New York], University of North Dakota [Grand Forks] (UND), Oregon Research Institute (ORI), University of California [San Diego] (UC San Diego), Universitat de Barcelona (UB), Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Hospital Universitario Mutua de Terrassa, School of Computer Science and Communication [Stockholm], Royal Institute of Technology [Stockholm] (KTH ), Jefferson (Philadelphia University + Thomas Jefferson University), University Medical Center Göttingen (UMG), Universität Heidelberg [Heidelberg] = Heidelberg University, Radboud University Medical Center [Nijmegen], Universitätsklinikum Frankfurt, Maastricht University [Maastricht], Institute of Psychological Medicine and Clinical Neurosciences, Aarhus University [Aarhus], University of Iowa [Iowa City], Universidade Federal do Rio Grande do Sul [Porto Alegre] (UFRGS), The Hospital for sick children [Toronto] (SickKids), Hospital de Clínicas de Porto Alegre (HCPA), Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), University of British Columbia (UBC), IRCCS Fondazione Stella Maris [Pisa], Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Universidade de Coimbra [Coimbra], Academic Centre on Rare Diseases (ACoRD), University College Dublin [Dublin] (UCD), Our Lady's Children's Hospital Crumlin (OLCHC), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Children’s Hospital Los Angeles [Los Angeles], Yale University [New Haven], Brown University, Institute of Neuroscience [Newcastle] (ION), Newcastle University [Newcastle], Department of Medical Epidemiology and Biostatistics (MEB), Division of Medical Genetics [Seattle], University of Illinois [Chicago] (UIC), University of Illinois System, Maine Medical Center Research Institute (MMCRI), Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre d’Etudes et de Recherches en Psychopathologie et Psychologie de la Santé (CERPPS), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Toulouse Mind & Brain Institut (TMBI), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Johns Hopkins University School of Medicine [Baltimore], Ludwig Maximilian University [Munich] (LMU), University of Michigan System, Department of Genetic Epidemiology in Psychiatry [Mannhein], Universität Heidelberg [Heidelberg] = Heidelberg University-Central Institute of Mental Health Mannheim, University of Dundee, National University of Ireland [Galway] (NUI Galway), University Hospital Basel [Basel], Neuroscience Research Australia (NeuRA), Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association, UNSW Faculty of Medicine [Sydney], University of New South Wales [Sydney] (UNSW), University of Chicago, Johns Hopkins University (JHU), Johns Hopkins Bloomberg School of Public Health [Baltimore], Dalhousie University [Halifax], Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada], State University of New York (SUNY), University Hospital of Cologne [Cologne], University of Adelaide, James Cook University (JCU), Institute for Molecular Bioscience, University of Queensland [Brisbane], Greifswald University Hospital, The University of Sydney, University Medical Center Groningen [Groningen] (UMCG), University of Calgary, University Health Network, Universidad de Antioquia = University of Antioquia [Medellín, Colombia], Universidade de São Paulo = University of São Paulo (USP), Ospedale San Raffaele, University of Amsterdam [Amsterdam] (UvA), University of Groningen [Groningen], Yale School of Medicine [New Haven, Connecticut] (YSM), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Cape Town, Cold Spring Harbor Laboratory (CSHL), Universidad de Sevilla / University of Sevilla, University of Florida [Gainesville] (UF), University of Denver, Purdue University [West Lafayette], Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Moscow Institute of Physics and Technology [Moscow] (MIPT), Sunnybrook Health Sciences Centre, Federal Institute of São Paulo (IFSP), Democritus University of Thrace (DUTH), Universiteit Gent = Ghent University (UGENT), Medical University of Warsaw - Poland, Sorbonne Université - Faculté de Médecine - Département d'Enseignement et de Recherche en Médecine Générale, Universitätsklinikum Essen [Universität Duisburg-Essen] (Uniklinik Essen), Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Institute of Mental Health [Singapore], Universidad de Cantabria [Santander], Tel Aviv University (TAU), University College Cork (UCC), University of Rochester [USA], Statens Serum Institut [Copenhagen], Софийски университет = Sofia University, Russian Academy of Sciences [Moscow] (RAS), Latvian Biomedical Research and Study Centre [Rīga], Vilnius University [Vilnius], Nanyang Technological University [Singapour], Department of Life Sciences, Imperial College London, Jena University Hospital [Jena], Oxford University Hospitals NHS Trust, Schizophrenia Research Institute [Sydney], Faculty of Science, Medicine and Health [Wollongong], University of Wollongong [Australia], City University of Hong Kong [Hong Kong] (CUHK), Lawrence Berkeley National Laboratory [Berkeley] (LBNL), This work was supported by grants 1R01MH10764901 and 5U01MH09443203 from the National Institute of Mental Health, as well as the Orion Farmos Research Foundation (V.A.) and the Fannie and John Hertz Foundation (H.K.F.). Consortium specific funding is detailed in the supplementary materials ('Study-specific acknowledgments')., Brainstorm Consortium, University of Kentucky, University of California [Irvine] (UCI), University of California-University of California, University of Pennsylvania [Philadelphia], Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 AMP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Universität Leipzig [Leipzig], Johannes Kepler University Linz [Linz] (JKU), University of Helsinki-University of Helsinki, University of Helsinki, University of Oxford [Oxford], University of Copenhagen = Københavns Universitet (KU), University of California [San Francisco] (UCSF), University of California, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Newcastle [Australia] (UoN), University of Virginia [Charlottesville], Universidade de Lisboa (ULISBOA), Università degli Studi di Salerno (UNISA), Rheinisch-Westfälische Technische Hochschule Aachen (RWTH), Università degli Studi di Perugia (UNIPG), Università degli studi della Campania 'Luigi Vanvitelli', Universität Heidelberg [Heidelberg], Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Universität Heidelberg [Heidelberg]-Central Institute of Mental Health Mannheim, VU University Amsterdam, Universidade de São Paulo (USP), Yale University School of Medicine, Universidad de Sevilla, Universiteit Gent = Ghent University [Belgium] (UGENT), Service de Psychiatrie de l'Enfant et de l'Adolescent [CHU Pitié-Salpêtrière] (SPEA), Tel Aviv University [Tel Aviv], University of Sofia, Anttila, Verneri, Bulik-Sullivan, Brendan, Finucane, Hilary K., Walters, Raymond K., Bras, Jose, Duncan, Laramie, Escott-Price, Valentina, Falcone, Guido J., Gormley, Padhraig, Malik, Rainer, Patsopoulos, Nikolaos A., Ripke, Stephan, Wei, Zhi, Yu, Dongmei, Lee, Phil H., Turley, Patrick, Grenier-Boley, Benjamin, Chouraki, Vincent, Kamatani, Yoichiro, Berr, Claudine, Letenneur, Luc, Hannequin, Didier, Amouyel, Philippe, Boland, Anne, Deleuze, Jean-Françoi, Duron, Emmanuelle, Vardarajan, Badri N., Reitz, Christiane, Goate, Alison M., Huentelman, Matthew J., Ilyas Kamboh, M., Larson, Eric B., Rogaeva, Ekaterina, George-Hyslop, Peter St, Hakonarson, Hakon, Kukull, Walter A., Farrer, Lindsay A., Barnes, Lisa L., Beach, Thomas G., Yesim Demirci, F., Head, Elizabeth, Hulette, Christine M., Jicha, Gregory A., Kauwe, John S.K., Kaye, Jeffrey A., Leverenz, James B., Levey, Allan I., Lieberman, Andrew P., Pankratz, Vernon S., Poon, Wayne W., Quinn, Joseph F., Saykin, Andrew J., Schneider, Lon S., Smith, Amanda G., Sonnen, Joshua A., Stern, Robert A., Van Deerlin, Vivianna M., Van Eldik, Linda J., Harold, Denise, Russo, Giancarlo, Rubinsztein, David C., Bayer, Anthony, Tsolaki, Magda, Proitsi, Petra, Fox, Nick C., Hampel, Harald, Owen, Michael J., Mead, Simon, Passmore, Peter, Morgan, Kevin, Nöthen, Markus M., Rossor, Martin, Lupton, Michelle K., Hoffmann, Per, Kornhuber, Johanne, Lawlor, Brian, McQuillin, Andrew, Al-Chalabi, Ammar, Bis, Joshua C., Ruiz, Agustin, Boada, Mercè, Seshadri, Sudha, Beiser, Alexa, Rice, Kenneth, Van Der Lee, Sven J., De Jager, Philip L., Geschwind, Daniel H., Riemenschneider, Matthia, Riedel-Heller, Steffi, Rotter, Jerome I., Ransmayr, Gerhard, Hyman, Bradley T., Cruchaga, Carlo, Alegret, Montserrat, Winsvold, Bendik, Palta, Priit, Farh, Kai-How, Cuenca-Leon, Ester, Furlotte, Nichola, Kurth, Tobia, Ligthart, Lannie, Terwindt, Gisela M., Freilinger, Tobia, Ran, Caroline, Gordon, Scott D., Borck, Guntram, Adams, Hieab H.H., Lehtimäki, Terho, Wedenoja, Juho, Buring, Julie E., Schürks, Marku, Hrafnsdottir, Maria, Hottenga, Jouke-Jan, Penninx, Brenda, Artto, Ville, Kaunisto, Mari, Vepsäläinen, Salli, Martin, Nicholas G., Montgomery, Grant W., Kurki, Mitja I., Hämäläinen, Eija, Huang, Hailiang, Huang, Jie, Sandor, Cynthia, Webber, Caleb, Muller-Myhsok, Bertram, Schreiber, Stefan, Salomaa, Veikko, Loehrer, Elizabeth, Göbel, Hartmut, Macaya, Alfon, Pozo-Rosich, Patricia, Hansen, Thoma, Werge, Thoma, Kaprio, Jaakko, Metspalu, Andre, Kubisch, Christian, Ferrari, Michel D., Belin, Andrea C., Van Den Maagdenberg, Arn M. 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Cahn, W, Cairns, M, Chong, S, Cohen, D, Crespo-Facorro, B, Crowley, J, Davidson, M, Delisi, L, Dinan, T, Donohoe, G, Drapeau, E, Duan, J, Haan, L, Hougaard, D, Karachanak-Yankova, S, Khrunin, A, Klovins, J, Kučinskas, V, Keong, J, Limborska, S, Loughland, C, Lönnqvist, J, Maher, B, Mattheisen, M, Mcdonald, C, Murphy, K, Nenadic, I, Van Os, J, Pantelis, C, Pato, M, Petryshen, T, Quested, D, Roussos, P, Sanders, A, Schall, U, Schwab, S, Sim, K, So, H, Stögmann, E, Subramaniam, M, Toncheva, D, Waddington, J, Walters, J, Weiser, M, Cheng, W, Cloninger, R, Curtis, D, Gejman, P, Henskens, F, Mattingsdal, M, Oh, S, Scott, R, Webb, B, Breen, G, Churchhouse, C, Bulik, C, Daly, M, Dichgans, M, Faraone, S, Guerreiro, R, Holmans, P, Kendler, K, Koeleman, B, Mathews, C, Price, A, Scharf, J, Sklar, P, Williams, J, Wood, N, Cotsapas, C, Palotie, A, Smoller, J, Sullivan, P, Rosand, J, Corvin, A, Neale, B, Kauwe, John S. K., Mcquillin, Andrew, Adams, Hieab H. H., Mccormack, Mark, Bau, Claiton H. D., Mcgough, James J., Mcintosh, Andrew, Andlauer, Till F. M., Macintyre, Donald J., Mcgrath, Lauren, Mclaughlin, Nicole, Delisi, Lynn, Mcdonald, Colm, Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement (Inserm U1167 - RID-AGE - Institut Pasteur), RIKEN Center for Integrative Medical Science, Neuropsychiatrie : recherche épidémiologique et clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), University of South Florida (USF), University of Zürich [Zürich] (UZH)-Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), Alzheimer Precision Medicine GRC n°21 (APM), CHU Pitié-Salpêtrière [APHP], Cardiff University-Medical Research Council, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Johannes Kepler University Linz [linz] (JKU), Washington University in St Louis, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Universitat Autònoma de Barcelona [Barcelona] (UAB), Hôpital Erasme (Bruxelles), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Jagiellonian University [Krakow] (UJ), Technische Universität Dresden (TUD), National and Kapodistrian University of Athens = University of Athens (NKUA | UoA), Charles University [Prague], Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), University of Bergen (UIB), University Medicine Goettingen, Università di Bologna [Bologna] (UNIBO), Forschungszentrum Jülich GmbH, UNSW Medicine [Sydney], McGill University, Universidad de Antioquia, University of Florida [Gainesville], Universiteit Gent [Ghent], Service Psychiatrie de l'Enfant et de l'Adolescent [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], University of Wollongong, Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 APM), Anttila, Verneri [0000-0002-0073-4675], Finucane, Hilary K [0000-0003-3864-9828], Walters, Raymond K [0000-0001-8422-6530], Duncan, Laramie [0000-0003-1131-661X], Escott-Price, Valentina [0000-0003-1784-5483], Falcone, Guido J [0000-0002-6407-0302], Gormley, Padhraig [0000-0002-8908-6968], Malik, Rainer [0000-0001-9212-2520], Ripke, Stephan [0000-0003-3622-835X], Wei, Zhi [0000-0001-6059-4267], Yu, Dongmei [0000-0001-7901-4365], Lee, Phil H [0000-0003-1770-3100], Breen, Gerome [0000-0003-2053-1792], Bulik, Cynthia M [0000-0001-7772-3264], Daly, Mark [0000-0002-0949-8752], Dichgans, Martin [0000-0002-0654-387X], Faraone, Stephen V [0000-0002-9217-3982], Holmans, Peter [0000-0003-0870-9412], Koeleman, Bobby [0000-0001-7749-182X], Mathews, Carol A [0000-0003-2208-7058], Sklar, Pamela [0000-0001-9715-4943], Williams, Julie [0000-0002-4069-0259], Wood, Nicholas W [0000-0002-9500-3348], Cotsapas, Chris [0000-0002-7772-5910], Smoller, Jordan W [0000-0002-0381-6334], Sullivan, Patrick [0000-0002-6619-873X], Rosand, Jonathan [0000-0002-1014-9138], Corvin, Aiden [0000-0001-6717-4089], Neale, Benjamin M [0000-0003-1513-6077], and Apollo - University of Cambridge Repository

Subjects
Etiology, [SDV]Life Sciences [q-bio], MESH: Brain Diseases, body-mass index, genetics [Mental Disorders], Disorders of the Brain, Risks factors, classification [Mental Disorders], MESH: Quantitative Trait, Heritable, MESH: Risk Factors, Risk Factors, MESH: Genetic Variation, alzheimers-disease, 610 Medicine & health, bipolar disorder, Brain Diseases, deficit hyperactivity disorder, Multidisciplinary, Mental Disorders, genetics [Brain Diseases], Brain Disease, Brain, Genetic Variation, Genome-Wide Association Study, Humans, Phenotype, Quantitative Trait, Heritable, Psychiatric Disorders, anorexia-nervosa, Mental Disorder, Psychiatric Genomics, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], long-term survival, Engineering sciences. Technology, Human, General Science & Technology, population-based twin, diagnosis [Mental Disorders], MESH: Phenotype, Neurological Disorders, Quantitative Trait, MD Multidisciplinary, MESH: Mental Disorders, diagnosis [Brain Diseases], Heritable, genetic correlations, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, major depressive disorder, Risk Factor, Brain Diseases/classification, Brain Diseases/diagnosis, Brain Diseases/genetics, Mental Disorders/classification, Mental Disorders/diagnosis, Mental Disorders/genetics, classification [Brain Diseases], Perturbações do Desenvolvimento Infantil e Saúde Mental, ddc:320, MESH: Genome-Wide Association Study, genome-wide association, Brainstorm Consortium, Genetic Factors, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities’ assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer’s disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important “scaffolding” to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders.

Published
2018

49. Migraine without aura: genome-wide association analysis identifies several novel susceptibility

Author

de Vries, Boukje, Freilinger, Tobias, Anttila, Verneri, Malik, Rainer, Kallela, Mikko, Terwindt, Gisela M, Pozo-Rosich, Patricia, Winsvold, Bendik, Nyholt, Dale R, van Oosterhout, Willebrordus PJ, Artto, Ville, Todt, Unda, Hämäläinen, Eija, Fernández-Morales, Jèssica, Louter, Mark A, Kaunisto, Mari A, Schoenen, Jean, Raitakari, Olli, Lehtimäki, Terho, Vila-Pueyo, Marta, Göbel, Hartmut, Wichmann, Erich, Sintas, Cèlia, Uitterlinden, Andre G, Hofman, Albert, Rivadeneira, Fernando, Heinze, Axel, Tronvik, Erling, van Duijn, Cornelia M, Kaprio, Jaakko, Cormand, Bru, Wessman, Maija, Frants, Rune R, Meitinger, Thomas, Müller-Myhsok, Bertram, Zwart, John-Anker, Färkkilä, Markus, Macaya, Alfons, Ferrari, Michel D, Kubisch, Christian, Palotie, Aarno, Dichgans, Martin, van den Maagdenberg, Arn MJM, and International Headache Genetics Consortium

Published
2013
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