Author: "Wessman, Maija" / Publication Year Range: Last 10 years - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Wessman, Maija"' showing total 100 results

Start Over Author "Wessman, Maija" Publication Year Range Last 10 years

100 results on '"Wessman, Maija"'

1. 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
Full Text: View/download PDF

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

Author: Bakker, Mark K., Kanning, Jos P., Abraham, Gad, Martinsen, Amy E., Winsvold, Bendik S., Zwart, John-Anker, Bourcier, Romain, Sawada, Tomonobu, Koido, Masaru, Kamatani, Yoichiro, Morel, Sandrine, Amouyel, Philippe, Debette, Stéphanie, Bijlenga, Philippe, Berrandou, Takiy, Ganesh, Santhi K., Bouatia-Naji, Nabila, Jones, Gregory, Bown, Matthew, Rinkel, Gabriel J.E., Veldink, Jan H., Ruigrok, Ynte M., Hege Aamodt, Anne, Heidi Skogholt, Anne, Brumpton, Ben M, Willer, Cristen J, Sandset, Else C, Kristoffersen, Espen S, Ellekjær, Hanne, Heuch, Ingrid, Nielsen, Jonas B, Hagen, Knut, Hveem, Kristian, Fritsche, Lars G, Thomas, Laurent F, Pedersen, Linda M, Gabrielsen, Maiken E, Holmen, Oddgeir L, Børte, Sigrid, Zhou, Wei, Abboud, Shérine, Pandolfo, Massimo, Thijs, Vincent, Leys, Didier, Bodenant, Marie, Louillet, Fabien, Touzé, Emmanuel, Mas, Jean-Louis, Samson, Yves, Leder, Sara, Léger, Anne, Deltour, Sandrine, Crozier, Sophie, Méresse, Isabelle, Canaple, Sandrine, Godefroy, Olivier, Giroud, Maurice, Béjot, Yannick, Decavel, Pierre, Medeiros, Elizabeth, Montiel, Paola, Moulin, Thierry, Vuillier, Fabrice, Dallongeville, Jean, Metso, Antti J, Metso, Tiina, Tatlisumak, Turgut, Grond-Ginsbach, Caspar, Lichy, Christoph, Kloss, Manja, Werner, Inge, Arnold, Marie-Luise, Dos Santos, Michael, Grau, Armin, Dichgans, Martin, Thomas-Feles, Constanze, Weber, Ralf, Brandt, Tobias, Pezzini, Alessandro, De Giuli, Valeria, Caria, Filomena, Poli, Loris, Padovani, Alessandro, Bersano, Anna, Lanfranconi, Silvia, Beretta, Simone, Ferrarese, Carlo, Giacolone, Giacomo, Paolucci, Stefano, Lyrer, Philippe, Engelter, Stefan, Fluri, Felix, Hatz, Florian, Gisler, Dominique, Bonati, Leo, Gensicke, Henrik, Amort, Margareth, Markus, Hugh, Majersik, Jennifer, Worrall, Bradford, Southerland, Andrew, Cole, John, Kittner, Steven, Evangelou, Evangelos, Warren, Helen R, Gao, He, Ntritsos, Georgios, Dimou, Niki, Esko, Tonu, Mägi, Reedik, Milani, Lili, Almgren, Peter, Boutin, Thibaud, Ding, Jun, Giulianini, Franco, Holliday, Elizabeth G, Jackson, Anne U, Li-Gao, Ruifang, Lin, Wei-Yu, Luan, Jian’an, Mangino, Massimo, Oldmeadow, Christopher, Peter Prins, Bram, Qian, Yong, Sargurupremraj, Muralidharan, Shah, Nabi, Surendran, Praveen, Thériault, Sébastien, Verweij, Niek, Willems, Sara M, Zhao, Jing-Hua, Connell, John, de Mutsert, Renée, Doney, Alex SF, Farrall, Martin, Menni, Cristina, Morris, Andrew D, Noordam, Raymond, Paré, Guillaume, Poulter, Neil R, Shields, Denis C, Stanton, Alice, Thom, Simon, Abecasis, Gonçalo, Amin, Najaf, Arking, Dan E, Ayers, Kristin L, Barbieri, Caterina M, Batini, Chiara, Bis, Joshua C, Blake, Tineka, Bochud, Murielle, Boehnke, Michael, Boerwinkle, Eric, Boomsma, Dorret I, Bottinger, Erwin P, Braund, Peter S, Brumat, Marco, Campbell, Archie, Campbell, Harry, Chakravarti, Aravinda, Chambers, John C, Chauhan, Ganesh, Ciullo, Marina, Cocca, Massimiliano, Collins, Francis, Cordell, Heather J, Davies, Gail, de Borst, Martin H, de Geus, Eco J, Deary, Ian J, Deelen, Joris, Del Greco M, Fabiola, Yusuf Demirkale, Cumhur, Dörr, Marcus, Ehret, Georg B, Elosua, Roberto, Enroth, Stefan, Mesut Erzurumluoglu, A, Ferreira, Teresa, Frånberg, Mattias, Franco, Oscar H, Gandin, Ilaria, Gasparini, Paolo, Giedraitis, Vilmantas, Gieger, Christian, Girotto, Giorgia, Goel, Anuj, Gow, Alan J, Gudnason, Vilmundur, Guo, Xiuqing, Gyllensten, Ulf, Hamsten, Anders, Harris, Tamara B, Harris, Sarah E, Hartman, Catharina A, Havulinna, Aki S, Hicks, Andrew A, Hofer, Edith, Hofman, Albert, Hottenga, Jouke-Jan, Huffman, Jennifer E, Hwang, Shih-Jen, Ingelsson, Erik, James, Alan, Jansen, Rick, Jarvelin, Marjo-Riitta, Joehanes, Roby, Johansson, Åsa, Johnson, Andrew D, Joshi, Peter K, Jousilahti, Pekka, Wouter Jukema, J, Jula, Antti, Kähönen, Mika, Kathiresan, Sekar, Keavney, Bernard D, Khaw, Kay-Tee, Knekt, Paul, Knight, Joanne, Kolcic, Ivana, Kooner, Jaspal S, Koskinen, Seppo, Kristiansson, Kati, Kutalik, Zoltan, Laan, Maris, Larson, Marty, Launer, Lenore J, Lehne, Benjamin, Lehtimäki, Terho, Liewald, David CM, Lin, Li, Lind, Lars, Lindgren, Cecilia M, Liu, YongMei, Loos, Ruth JF, Lopez, Lorna M, Lu, Yingchang, Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Mamasoula, Chrysovalanto, Marrugat, Jaume, Marten, Jonathan, Milaneschi, Yuri, Morgan, Anna, Morris, Andrew P, Morrison, Alanna C, Munson, Peter J, Nalls, Mike A, Nandakumar, Priyanka, Nelson, Christopher P, Niiranen, Teemu, Nolte, Ilja M, Nutile, Teresa, Oldehinkel, Albertine J, Oostra, Ben A, O’Reilly, Paul F, Org, Elin, Padmanabhan, Sandosh, Palmas, Walter, Palotie, Aarno, Pattie, Alison, WJH Penninx, Brenda, Perola, Markus, Peters, Annette, Polasek, Ozren, Pramstaller, Peter P, Tri Nguyen, Quang, Raitakari, Olli T, Rettig, Rainer, Rice, Kenneth, Ridker, Paul M, Ried, Janina S, Riese, Harriëtte, Ripatti, Samuli, Robino, Antonietta, Rose, Lynda M, Rotter, Jerome I, Rudan, Igor, Ruggiero, Daniela, Saba, Yasaman, Sala, Cinzia F, Salomaa, Veikko, Samani, Nilesh J, Sarin, Antti-Pekka, Schmidt, Reinhold, Schmidt, Helena, Shrine, Nick, Siscovick, David, Smith, Albert V, Snieder, Harold, Sõber, Siim, Sorice, Rossella, Starr, John M, Stott, David J, Strachan, David P, Strawbridge, Rona J, Sundström, Johan, Swertz, Morris A, Taylor, Kent D, Teumer, Alexander, Tobin, Martin D, Tomaszewski, Maciej, Toniolo, Daniela, Traglia, Michela, Trompet, Stella, Tuomilehto, Jaakko, Tzourio, Christophe, Uitterlinden, André G, Vaez, Ahmad, van der Most, Peter J, van Duijn, Cornelia M, Verwoert, Germaine C, Vitart, Veronique, Völker, Uwe, Vollenweider, Peter, Vuckovic, Dragana, Watkins, Hugh, Wild, Sarah H, Willemsen, Gonneke, Wilson, James F, Wright, Alan F, Yao, Jie, Zemunik, Tatijana, Zhang, Weihua, Attia, John R, Butterworth, Adam S, Chasman, Daniel I, Conen, David, Cucca, Francesco, Danesh, John, Hayward, Caroline, Howson, Joanna MM, Laakso, Markku, Lakatta, Edward G, Langenberg, Claudia, Melander, Olle, Mook-Kanamori, Dennis O, Palmer, Colin NA, Risch, Lorenz, Scott, Robert A, Scott, Rodney J, Sever, Peter, Spector, Tim D, van der Harst, Pim, Wareham, Nicholas J, Zeggini, Eleftheria, Levy, Daniel, Munroe, Patricia B, Newton-Cheh, Christopher, Brown, Morris J, Metspalu, Andres, Psaty, Bruce M., Wain, Louise V, Elliott, Paul, Caulfield, Mark J, Gormley, Padhraig, Anttila, Verneri, Palta, Priit, Esko, Tonu, Pers, Tune H, Farh, Kai-How, Cuenca-Leon, Ester, Muona, Mikko, Furlotte, Nicholas A, Kurth, Tobias, Ingason, Andres, McMahon, George, Ligthart, Lannie, Terwindt, Gisela M, Kallela, Mikko, Freilinger, Tobias M, Ran, Caroline, Gordon, Scott G, Stam, Anine H, Steinberg, Stacy, Borck, Guntram, Koiranen, Markku, Quaye, Lydia, Adams, Hieab H H, Lehtimäki, Terho, Sarin, Antti-Pekka, Wedenoja, Juho, Hinds, David A, Buring, Julie E, Schürks, Markus, Ridker, Paul M, Gudlaug Hrafnsdottir, Maria, Stefansson, Hreinn, Ring, Susan M, Hottenga, Jouke-Jan, Penninx, Brenda W J H, Färkkilä, Markus, Artto, Ville, Kaunisto, Mari, Vepsäläinen, Salli, Malik, Rainer, Heath, Andrew C, Madden, Pamela A F, Martin, Nicholas G, Montgomery, Grant W, Kurki, Mitja I, Kals, Mart, Mägi, Reedik, Pärn, Kalle, Hämäläinen, Eija, Huang, Hailiang, Byrnes, Andrea E, Franke, Lude, Huang, Jie, Stergiakouli, Evie, Lee, Phil H, Sandor, Cynthia, Webber, Caleb, Cader, Zameel, Muller-Myhsok, Bertram, Schreiber, Stefan, Meitinger, Thomas, Eriksson, Johan G, Salomaa, Veikko, Heikkilä, Kauko, Loehrer, Elizabeth, Uitterlinden, Andre G, Hofman, Albert, van Duijn, Cornelia M, Cherkas, Lynn, Pedersen, Linda M, Stubhaug, Audun, Nielsen, Christopher S, Männikkö, Minna, Mihailov, Evelin, Milani, Lili, Göbel, Hartmut, Esserlind, Ann-Louise, Francke Christensen, Anne, Folkmann Hansen, Thomas, Werge, Thomas, Kaprio, Jaakko, Aromaa, Arpo J, Raitakari, Olli, Arfan Ikram, M, Spector, Tim, Järvelin, Marjo-Riitta, Metspalu, Andres, Kubisch, Christian, Strachan, David P, Ferrari, Michel D, Belin, Andrea C, Dichgans, Martin, Wessman, Maija, van den Maagdenberg, Arn M J M, Boomsma, Dorret I, Davey Smith, George, Stefansson, Kari, Eriksson, Nicholas, Daly, Mark J, Neale, Benjamin M, Olesen, Jes, Chasman, Daniel I, Nyholt, Dale R, Palotie, Aarno, Akiyama, Masato, Alg, Varinder S., Børte, Sigrid, Broderick, Joseph P., Brumpton, Ben M., Dauvillier, Jérôme, Desal, Hubert, Dina, Christian, Friedrich, Christoph M., Gaál-Paavola, Emília I., Gentric, Jean-Christophe, Hirsch, Sven, Hostettler, Isabel C., Houlden, Henry, Hveem, Kristian, Jääskeläinen, Juha E., Johnsen, Marianne Bakke, Li, Liming, Lin, Kuang, Lindgren, Antti, Martin, Olivier, Matsuda, Koichi, Millwood, Iona Y., Naggara, Olivier, Niemelä, Mika, Pera, Joanna, Redon, Richard, Rouleau, Guy A., Sandvei, Marie Søfteland, Schilling, Sabine, Shotar, Eimad, Slowik, Agnieszka, Terao, Chikashi, Verschuren, W. M. Monique, Walters, Robin G., Werring, David J., Willer, Cristen J., Woo, Daniel, Worrall, Bradford B., and Zhou, Sirui
Published: 2023
Full Text: View/download PDF

3. High-resolution population-specific recombination rates and their effect on phasing and genotype imputation

Author: Hassan, Shabbeer, Surakka, Ida, Taskinen, Marja-Riitta, Salomaa, Veikko, Palotie, Aarno, Wessman, Maija, Tukiainen, Taru, Pirinen, Matti, Palta, Priit, and Ripatti, Samuli
Published: 2021
Full Text: View/download PDF

4. 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

5. 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
Full Text: View/download PDF

6. Genetics of migraine

Author: Anttila, Verneri, primary, Wessman, Maija, additional, Kallela, Mikko, additional, and Palotie, Aarno, additional
Published: 2018
Full Text: View/download PDF

7. 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
Full Text: View/download PDF

8. NCOR2 is a novel candidate gene for migraine-epilepsy phenotype

Author: Nuottamo, Marjo Eveliina, Häppölä, Paavo, Artto, Ville, Hautakangas, Heidi, Pirinen, Matti, Hiekkalinna, Tero, Ellonen, Pekka, Lepistö, Maija, Hämäläinen, Eija, Siren, Auli, Lehesjoki, Anna-Elina, Kallela, Mikko, Palotie, Aarno, Kaunisto, Mari Anneli, Wessman, Maija, Institute for Molecular Medicine Finland, Helsinki Institute of Life Science HiLIFE, Complex Disease Genetics, Genomics of Neurological and Neuropsychiatric Disorders, University of Helsinki, Clinicum, HUS Helsinki and Uusimaa Hospital District, HUS Neurocenter, Neurologian yksikkö, Statistical and population genetics, Centre of Excellence in Complex Disease Genetics, Helsinki Institute for Information Technology, Department of Mathematics and Statistics, Biostatistics Helsinki, Department of Public Health, Medicum, Quantitative Genetics, Department of Medical and Clinical Genetics, and Department of Neurosciences
Subjects: IDENTIFICATION, MUTATIONS, FAMILIAL HEMIPLEGIC MIGRAINE, 3112 Neurosciences, General Medicine, RETT-SYNDROME, MECP2, 12q24, comorbidity, RESOURCE, LINKAGE, PROGRAM, linkage analysis, Neurology (clinical), next-generation sequencing (NGS) technologies, Neurological disorder, pathophysiology
Abstract: Hypothesis To identify genetic factors predisposing to migraine-epilepsy phenotype utilizing a multi-generational family with known linkage to chr12q24.2-q24.3. Methods We used single nucleotide polymorphism (SNP) genotyping and next-generation sequencing technologies to perform linkage, haplotype, and variant analyses in an extended Finnish migraine-epilepsy family (n = 120). In addition, we used a large genome-wide association study (GWAS) dataset of migraine and two biobank studies, UK Biobank and FinnGen, to test whether variants within the susceptibility region associate with migraine or epilepsy related phenotypes in a population setting. Results The family showed the highest evidence of linkage (LOD 3.42) between rs7966411 and epilepsy. The haplotype shared among 12 out of 13 epilepsy patients in the family covers almost the entire NCOR2 and co-localizes with one of the risk loci of the recent GWAS on migraine. The haplotype harbors nine low-frequency variants with potential regulatory functions. Three of them, in addition to two common variants, show nominal associations with neurological disorders in either UK Biobank or FinnGen. Conclusion We provide several independent lines of evidence supporting association between migraine-epilepsy phenotype and NCOR2. Our study suggests that NCOR2 may have a role in both migraine and epilepsy and thus would provide evidence for shared pathophysiology underlying these two diseases.
Published: 2022

9. Polygenic risk provides biological validity for the ICHD-3 criteria among Finnish migraine families

Author: Häppölä, Paavo, Gormley, Padhraig, Nuottamo, Marjo E., Artto, Ville, Sumelahti, Marja Liisa, Nissilä, Markku, Keski-Säntti, Petra, Ilmavirta, Matti, Kaunisto, Mari A., Hämäläinen, Eija I., Ripatti, Samuli, Pirinen, Matti, Wessman, Maija, Palotie, Aarno, Kallela, Mikko, Hansen, Thomas Folkmann, Olesen, Jes, Häppölä, Paavo, Gormley, Padhraig, Nuottamo, Marjo E., Artto, Ville, Sumelahti, Marja Liisa, Nissilä, Markku, Keski-Säntti, Petra, Ilmavirta, Matti, Kaunisto, Mari A., Hämäläinen, Eija I., Ripatti, Samuli, Pirinen, Matti, Wessman, Maija, Palotie, Aarno, Kallela, Mikko, Hansen, Thomas Folkmann, and Olesen, Jes
Abstract: Background: Migraine is diagnosed using the extensively field-tested International Classification of Headache Disorders (ICHD-3) consensus criteria derived by the International Headache Society. To evaluate the criteria in respect to a measurable biomarker, we studied the relationship between the main ICHD-3 criteria and the polygenic risk score, a measure of common variant burden in migraine. Methods: We used linear mixed models to study the correlation of ICHD-3 diagnostic criteria, underlying symptoms, and main diagnoses with the polygenic risk score of migraine in a cohort of 8602 individuals from the Finnish Migraine Genome Project. Results: Main diagnostic categories and all underlying diagnostic criteria formed a consistent continuum along the increasing polygenic burden. Polygenic risk was associated with the heterogeneous clinical picture starting from the non-migraine headache (mean 0.07; 95% CI 0.02–0.12; p = 0.008 compared to the non-headache group), to probable migraine (mean 0.13; 95% CI 0.08–0.18; p < 0.001), migraine headache (mean 0.17; 95% CI 0.14–0.21; p < 0.001) and migraine with typical visual aura (mean 0.29; 95% CI 0.26–0.33; p < 0.001), all the way to the hemiplegic aura (mean 0.37; 95% CI 0.31–0.43; p < 0.001). All individual ICHD-3 symptoms and the total number of reported symptoms, a surrogate of migraine complexity, demonstrated a clear inclination with an increasing polygenic risk. Conclusions: The complex migraine phenotype progressively follows the polygenic burden from individuals with no headache to non-migrainous headache and up to patients with attacks manifesting all the features of the ICHD-3 headache and aura. Results provide further biological support for the ICHD-3 diagnostic criteria.
Published: 2022

10. Cross-trait analyses with migraine reveal widespread pleiotropy and suggest a vascular component to migraine headache

Author: The International Headache Genetics Consortium, Siewert, Katherine M., Klarin, Derek, Damrauer, Scott M., Chang, Kyong Mi, Tsao, Philip S., Assimes, Themistocles L., Smith, George Davey, Voight, Benjamin F., Anttila, Verneri, Palta, Priit, Muona, Mikko, Kallela, Kaarlo Mikko, Koiranen, Markku, Lehtimäki, Terho, Sarin, Antti-Pekka, Wedenoja, Juho, Färkkilä, Markus, Artto, Ville, Kaunisto, Mari, Vepsäläinen, Salli, Kurki, Mitja Ilari, Hämäläinen, Eija Inkeri, Eriksson, Johan G., Salomaa, Veikko, Heikkilä, Kauko, Männikkö, Minna, Hiekkala, Marjo, Kajanne, Risto, Kaprio, Jaakko, Aromaa, Arpo J., Raitakari, Olli, Järvelin, Marjo-Riitta, Wessman, Maija, Palotie, Aarno, Radiology & Nuclear Medicine, Epidemiology, Internal Medicine, Institute for Molecular Medicine Finland, Genomics of Neurological and Neuropsychiatric Disorders, Medicum, HUS Neurocenter, Clinicum, Department of Neurosciences, Department of Public Health, Neurologian yksikkö, HUS Helsinki and Uusimaa Hospital District, Research Programs Unit, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, Centre of Excellence in Complex Disease Genetics, Biosciences, and Aarno Palotie / Principal Investigator
Subjects: 0301 basic medicine, Linkage disequilibrium, Genetic correlation, Epidemiology, Migraine Disorders, Population, Genome-wide association study, Bioinformatics, Corrections, 3124 Neurology and psychiatry, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Pleiotropy, Pleiotropism, Mendelian randomization, Humans, Medicine, AcademicSubjects/MED00860, migraine, education, Migraine, education.field_of_study, business.industry, Headache, 3112 Neurosciences, Genetic Pleiotropy, Mendelian Randomization Analysis, General Medicine, medicine.disease, Miscellaneous, Phenotype, 030104 developmental biology, Migranya, Cefalàlgia, business, headache, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Background Nearly a fifth of the world’s population suffer from migraine headache, yet risk factors for this disease are poorly characterized. Methods To further elucidate these factors, we conducted a genetic correlation analysis using cross-trait linkage disequilibrium (LD) score regression between migraine headache and 47 traits from the UK Biobank. We then tested for possible causality between these phenotypes and migraine, using Mendelian randomization. In addition, we attempted replication of our findings in an independent genome-wide association study (GWAS) when available. Results We report multiple phenotypes with genetic correlation (P < 1.06 × 10−3) with migraine, including heart disease, type 2 diabetes, lipid levels, blood pressure, autoimmune and psychiatric phenotypes. In particular, we find evidence that blood pressure directly contributes to migraine and explains a previously suggested causal relationship between calcium and migraine. Conclusions This is the largest genetic correlation analysis of migraine headache to date, both in terms of migraine GWAS sample size and the number of phenotypes tested. We find that migraine has a shared genetic basis with a large number of traits, indicating pervasive pleiotropy at migraine-associated loci.
Published: 2020

11. sj-pdf-7-cep-10.1177_03331024211068065 - Supplemental material for NCOR2 is a novel candidate gene for migraine-epilepsy phenotype

Author: Nuottamo, Marjo Eveliina, H��pp��l��, Paavo, Artto, Ville, Hautakangas, Heidi, Pirinen, Matti, Hiekkalinna, Tero, Ellonen, Pekka, Lepist��, Maija, H��m��l��inen, Eija, Siren, Auli, Lehesjoki, Anna-Elina, Kallela, Mikko, Palotie, Aarno, Kaunisto, Mari Anneli, and Wessman, Maija
Subjects: FOS: Psychology, FOS: Clinical medicine, 170199 Psychology not elsewhere classified, 110319 Psychiatry (incl. Psychotherapy), 110306 Endocrinology, 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified, 110904 Neurology and Neuromuscular Diseases, Neuroscience
Abstract: Supplemental material, sj-pdf-7-cep-10.1177_03331024211068065 for NCOR2 is a novel candidate gene for migraine-epilepsy phenotype by Marjo Eveliina Nuottamo, Paavo H��pp��l��, Ville Artto, Heidi Hautakangas, Matti Pirinen, Tero Hiekkalinna, Pekka Ellonen, Maija Lepist��, Eija H��m��l��inen, International Headache Genetics Consortium (IHGC), FinnGenConsortiumAuli Siren, Anna-Elina Lehesjoki, Mikko Kallela, Aarno Palotie, Mari Anneli Kaunisto and Maija Wessman in Cephalalgia
Published: 2022
Full Text: View/download PDF

12. sj-pdf-2-cep-10.1177_03331024211068065 - Supplemental material for NCOR2 is a novel candidate gene for migraine-epilepsy phenotype

Author: Nuottamo, Marjo Eveliina, H��pp��l��, Paavo, Artto, Ville, Hautakangas, Heidi, Pirinen, Matti, Hiekkalinna, Tero, Ellonen, Pekka, Lepist��, Maija, H��m��l��inen, Eija, Siren, Auli, Lehesjoki, Anna-Elina, Kallela, Mikko, Palotie, Aarno, Kaunisto, Mari Anneli, and Wessman, Maija
Subjects: FOS: Psychology, FOS: Clinical medicine, 170199 Psychology not elsewhere classified, 110319 Psychiatry (incl. Psychotherapy), 110306 Endocrinology, 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified, 110904 Neurology and Neuromuscular Diseases, Neuroscience
Abstract: Supplemental material, sj-pdf-2-cep-10.1177_03331024211068065 for NCOR2 is a novel candidate gene for migraine-epilepsy phenotype by Marjo Eveliina Nuottamo, Paavo H��pp��l��, Ville Artto, Heidi Hautakangas, Matti Pirinen, Tero Hiekkalinna, Pekka Ellonen, Maija Lepist��, Eija H��m��l��inen, International Headache Genetics Consortium (IHGC), FinnGenConsortiumAuli Siren, Anna-Elina Lehesjoki, Mikko Kallela, Aarno Palotie, Mari Anneli Kaunisto and Maija Wessman in Cephalalgia
Published: 2022
Full Text: View/download PDF

13. sj-pdf-1-cep-10.1177_03331024211068065 - Supplemental material for NCOR2 is a novel candidate gene for migraine-epilepsy phenotype

Author: Nuottamo, Marjo Eveliina, H��pp��l��, Paavo, Artto, Ville, Hautakangas, Heidi, Pirinen, Matti, Hiekkalinna, Tero, Ellonen, Pekka, Lepist��, Maija, H��m��l��inen, Eija, Siren, Auli, Lehesjoki, Anna-Elina, Kallela, Mikko, Palotie, Aarno, Kaunisto, Mari Anneli, and Wessman, Maija
Subjects: FOS: Psychology, FOS: Clinical medicine, 170199 Psychology not elsewhere classified, 110319 Psychiatry (incl. Psychotherapy), 110306 Endocrinology, 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified, 110904 Neurology and Neuromuscular Diseases, Neuroscience
Abstract: Supplemental material, sj-pdf-1-cep-10.1177_03331024211068065 for NCOR2 is a novel candidate gene for migraine-epilepsy phenotype by Marjo Eveliina Nuottamo, Paavo H��pp��l��, Ville Artto, Heidi Hautakangas, Matti Pirinen, Tero Hiekkalinna, Pekka Ellonen, Maija Lepist��, Eija H��m��l��inen, International Headache Genetics Consortium (IHGC), FinnGenConsortiumAuli Siren, Anna-Elina Lehesjoki, Mikko Kallela, Aarno Palotie, Mari Anneli Kaunisto and Maija Wessman in Cephalalgia
Published: 2022
Full Text: View/download PDF

14. sj-pdf-3-cep-10.1177_03331024211068065 - Supplemental material for NCOR2 is a novel candidate gene for migraine-epilepsy phenotype

Author: Nuottamo, Marjo Eveliina, H��pp��l��, Paavo, Artto, Ville, Hautakangas, Heidi, Pirinen, Matti, Hiekkalinna, Tero, Ellonen, Pekka, Lepist��, Maija, H��m��l��inen, Eija, Siren, Auli, Lehesjoki, Anna-Elina, Kallela, Mikko, Palotie, Aarno, Kaunisto, Mari Anneli, and Wessman, Maija
Subjects: FOS: Psychology, FOS: Clinical medicine, 170199 Psychology not elsewhere classified, 110319 Psychiatry (incl. Psychotherapy), 110306 Endocrinology, 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified, 110904 Neurology and Neuromuscular Diseases, Neuroscience
Abstract: Supplemental material, sj-pdf-3-cep-10.1177_03331024211068065 for NCOR2 is a novel candidate gene for migraine-epilepsy phenotype by Marjo Eveliina Nuottamo, Paavo H��pp��l��, Ville Artto, Heidi Hautakangas, Matti Pirinen, Tero Hiekkalinna, Pekka Ellonen, Maija Lepist��, Eija H��m��l��inen, International Headache Genetics Consortium (IHGC), FinnGenConsortiumAuli Siren, Anna-Elina Lehesjoki, Mikko Kallela, Aarno Palotie, Mari Anneli Kaunisto and Maija Wessman in Cephalalgia
Published: 2022
Full Text: View/download PDF

15. sj-pdf-5-cep-10.1177_03331024211068065 - Supplemental material for NCOR2 is a novel candidate gene for migraine-epilepsy phenotype

Author: Nuottamo, Marjo Eveliina, H��pp��l��, Paavo, Artto, Ville, Hautakangas, Heidi, Pirinen, Matti, Hiekkalinna, Tero, Ellonen, Pekka, Lepist��, Maija, H��m��l��inen, Eija, Siren, Auli, Lehesjoki, Anna-Elina, Kallela, Mikko, Palotie, Aarno, Kaunisto, Mari Anneli, and Wessman, Maija
Subjects: FOS: Psychology, FOS: Clinical medicine, 170199 Psychology not elsewhere classified, 110319 Psychiatry (incl. Psychotherapy), 110306 Endocrinology, 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified, 110904 Neurology and Neuromuscular Diseases, Neuroscience
Abstract: Supplemental material, sj-pdf-5-cep-10.1177_03331024211068065 for NCOR2 is a novel candidate gene for migraine-epilepsy phenotype by Marjo Eveliina Nuottamo, Paavo H��pp��l��, Ville Artto, Heidi Hautakangas, Matti Pirinen, Tero Hiekkalinna, Pekka Ellonen, Maija Lepist��, Eija H��m��l��inen, International Headache Genetics Consortium (IHGC), FinnGenConsortiumAuli Siren, Anna-Elina Lehesjoki, Mikko Kallela, Aarno Palotie, Mari Anneli Kaunisto and Maija Wessman in Cephalalgia
Published: 2022
Full Text: View/download PDF

16. sj-pdf-6-cep-10.1177_03331024211068065 - Supplemental material for NCOR2 is a novel candidate gene for migraine-epilepsy phenotype

Author: Nuottamo, Marjo Eveliina, H��pp��l��, Paavo, Artto, Ville, Hautakangas, Heidi, Pirinen, Matti, Hiekkalinna, Tero, Ellonen, Pekka, Lepist��, Maija, H��m��l��inen, Eija, Siren, Auli, Lehesjoki, Anna-Elina, Kallela, Mikko, Palotie, Aarno, Kaunisto, Mari Anneli, and Wessman, Maija
Subjects: FOS: Psychology, FOS: Clinical medicine, 170199 Psychology not elsewhere classified, 110319 Psychiatry (incl. Psychotherapy), 110306 Endocrinology, 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified, 110904 Neurology and Neuromuscular Diseases, Neuroscience
Abstract: Supplemental material, sj-pdf-6-cep-10.1177_03331024211068065 for NCOR2 is a novel candidate gene for migraine-epilepsy phenotype by Marjo Eveliina Nuottamo, Paavo H��pp��l��, Ville Artto, Heidi Hautakangas, Matti Pirinen, Tero Hiekkalinna, Pekka Ellonen, Maija Lepist��, Eija H��m��l��inen, International Headache Genetics Consortium (IHGC), FinnGenConsortiumAuli Siren, Anna-Elina Lehesjoki, Mikko Kallela, Aarno Palotie, Mari Anneli Kaunisto and Maija Wessman in Cephalalgia
Published: 2022
Full Text: View/download PDF

17. Author Correction: The mutational constraint spectrum quantified from variation in 141,456 humanS

Author: Karczewski, Konrad J., Francioli, Laurent C., Tiao, Grace, Cummings, Beryl B., Alföldi, Jessica, Wang, Qingbo, Collins, Ryan L., Laricchia, Kristen M., Ganna, Andrea, Birnbaum, Daniel P., Gauthier, Laura D., Brand, Harrison, Solomonson, Matthew, Rhodes, Daniel, Singer-Berk, Moriel, England, Eleina M., Seaby, Eleanor G., Kosmicki, Jack A., Walters, Raymond K., Tashman, Katherine, Farjoun, Yossi, Banks, Eric, Poterba, Timothy, Wang, Arcturus, Seed, Cotton, Whiffin, Nicola, Chong, Jessica X., Samocha, Kaitlin E., Pierce-Hoffman, Emma, Zappala, Zachary, O’Donnell-Luria, Anne H., Minikel, Eric Vallabh, Weisburd, Ben, Lek, Monkol, Ware, James S., Vittal, Christopher, Armean, Irina M., Bergelson, Louis, Cibulskis, Kristian, Connolly, Kristen M., Covarrubias, Miguel, Donnelly, Stacey, Ferriera, Steven, Gabriel, Stacey, Gentry, Jeff, Gupta, Namrata, Jeandet, Thibault, Kaplan, Diane, Llanwarne, Christopher, Munshi, Ruchi, Novod, Sam, Petrillo, Nikelle, Roazen, David, Ruano-Rubio, Valentin, Saltzman, Andrea, Schleicher, Molly, Soto, Jose, Tibbetts, Kathleen, Tolonen, Charlotte, Wade, Gordon, Talkowski, Michael E., Aguilar Salinas, Carlos A., Ahmad, Tariq, Albert, Christine M., Ardissino, Diego, Atzmon, Gil, Barnard, John, Beaugerie, Laurent, Benjamin, Emelia J., Boehnke, Michael, Bonnycastle, Lori L., Bottinger, Erwin P., Bowden, Donald W., Bown, Matthew J., Chambers, John C., Chan, Juliana C., Chasman, Daniel, Cho, Judy, Chung, Mina K., Cohen, Bruce, Correa, Adolfo, Dabelea, Dana, Daly, Mark J., Darbar, Dawood, Duggirala, Ravindranath, Dupuis, Josée, Ellinor, Patrick T., Elosua, Roberto, Erdmann, Jeanette, Esko, Tõnu, Färkkilä, Martti, Florez, Jose, Franke, Andre, Getz, Gad, Glaser, Benjamin, Glatt, Stephen J., Goldstein, David, Gonzalez, Clicerio, Groop, Leif, Haiman, Christopher, Hanis, Craig, Harms, Matthew, Hiltunen, Mikko, Holi, Matti M., Hultman, Christina M., Kallela, Mikko, Kaprio, Jaakko, Kathiresan, Sekar, Kim, Bong Jo, Kim, Young Jin, Kirov, George, Kooner, Jaspal, Koskinen, Seppo, Krumholz, Harlan M., Kugathasan, Subra, Kwak, Soo Heon, Laakso, Markku, Lehtimäki, Terho, Loos, Ruth J.F., Lubitz, Steven A., Ma, Ronald C.W., MacArthur, Daniel G., Marrugat, Jaume, Mattila, Kari M., McCarthy, Mark I., McGovern, Dermot, McPherson, Ruth, Meigs, James B., Melander, Olle, Metspalu, Andres, Neale, Benjamin M., Nilsson, Peter M., O’Donovan, Michael C., Ongur, Dost, Orozco, Lorena, Palotie, Aarno, Park, Kyong Soo, Pato, Carlos, Pulver, Ann E., Rahman, Nazneen, Remes, Anne M., Rioux, John D., Ripatti, Samuli, Roden, Dan M., Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Scharf, Jeremiah, Schunkert, Heribert, Shoemaker, Moore B., Sklar, Pamela, Soininen, Hilkka, Sokol, Harry, Spector, Tim, Sullivan, Patrick F., Suvisaari, Jaana, Tai, E. Shyong, Teo, Yik Ying, Tiinamaija, Tuomi, Tsuang, Ming, Turner, Dan, Tusie-Luna, Teresa, Vartiainen, Erkki, Vawter, Marquis P., Watkins, Hugh, Weersma, Rinse K., Wessman, Maija, and Xavier, Ramnik J.
Subjects: Multidisciplinary, Science & Technology, General Science & Technology, Spectrum (functional analysis), Rare variants, Biology, Constraint (information theory), Multidisciplinary Sciences, Variation (linguistics), Genome Aggregation Database Consortium, Science & Technology - Other Topics, Author Correction, Medical genomics, Algorithm
Abstract: In this Article, author Marquis P. Vawter was missing from the Genome Aggregation Database Consortium list. They are associated with the affiliation: ‘Department of Psychiatry & Human Behavior, University of California Irvine, Irvine, CA, USA’, and contributed to the generation of the primary data incorporated into the gnomAD resource. In addition, in the legend to Fig. 1, ‘ten’ should have been ‘seven’ in the sentence: “a, Uniform manifold approximation and projection (UMAP)46,47 plot depicting the ancestral diversity of all individuals in gnomAD, using seven principal components.” The original Article has been corrected online.
Published: 2021

18. sj-pdf-1-cep-10.1177_03331024211045651 - Supplemental material for Polygenic risk provides biological validity for the ICHD-3 criteria among Finnish migraine families

Author: Häppölä, Paavo, Gormley, Padhraig, Nuottamo, Marjo E, Artto, Ville, Sumelahti, Marja-Liisa, Nissilä, Markku, Keski-Säntti, Petra, Ilmavirta, Matti, Kaunisto, Mari A, Hämäläinen, Eija I, Ripatti, Samuli, Pirinen, Matti, Wessman, Maija, Palotie, Aarno, and Kallela, Mikko
Subjects: FOS: Psychology, FOS: Clinical medicine, 170199 Psychology not elsewhere classified, 110319 Psychiatry (incl. Psychotherapy), 110306 Endocrinology, 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified, 110904 Neurology and Neuromuscular Diseases, Neuroscience
Abstract: Supplemental material, sj-pdf-1-cep-10.1177_03331024211045651 for Polygenic risk provides biological validity for the ICHD-3 criteria among Finnish migraine families by Paavo Häppölä, Padhraig Gormley, Marjo E Nuottamo, Ville Artto, Marja-Liisa Sumelahti, Markku Nissilä, Petra Keski-Säntti, Matti Ilmavirta, Mari A Kaunisto, Eija I Hämäläinen, Samuli Ripatti, Matti Pirinen, Maija Wessman, Aarno Palotie, Mikko Kallela and International Headache Genetics Consortium (IHGC) in Cephalalgia
Published: 2021
Full Text: View/download PDF

19. Migreenin geneettinen tausta on monitekijäinen

Author: Wessman, Maija, Nuottamo, Marjo, Kaunisto, Mari, Häppölä, Paavo, Artto, Ville, Kallela, Mikko, Anttila, Verneri, Palotie, Aarno, Suomen molekyylilääketieteen instituutti, Biotieteet, Genomics of Neurological and Neuropsychiatric Disorders, Helsinki Institute of Life Science HiLIFE, Helsingin yliopisto, Complex Disease Genetics, Clinicum, HUS Helsingin ja Uudenmaan sairaanhoitopiiri, HUS Neurokeskus, Neurologian yksikkö, Neurotieteiden osasto, Aarno Palotie / Vastuullinen tutkija, and Centre of Excellence in Complex Disease Genetics
Subjects: 3111 Biolääketieteet, 3112 Neurotieteet
Abstract: Vertaisarvioitu. Migreeni on yleinen neurovaskulaarinen aivosairaus, jolla on vahva geneettinen tausta. Migreenin molekyyligeneettiset tutkimukset 1990-luvulla kohdistuivat harvinaiseen hemiplegiseen migreeniin, joka osoittautui ionikanavataudiksi. Yleisten migreenimuotojen geneettinen tausta alkoi hahmottua 2010-luvulla genominlaajuisten assosiaatiotutkimusten (GWAS) avulla. Tutkimukset ovat paljastaneet kymmeniä yleisiä, vaikutukseltaan vähäisiä migreenin geneettisiä riskivariantteja, erityisesti vaskulaarisissa kudoksissa ilmenevistä geeneistä. On selvinnyt, että aurallisen, aurattoman ja hemiplegisen migreenin riskivariantit ovat osittain samoja. Yleisten riskivarianttien yhteisvaikutus taas selittää migreenin kertymistä perheisiin. Mielenkiintoista on myös se, että migreenillä on yhteisiä geneettisiä riskitekijöitä psyykkisten sairauksien, erityisesti ADHD:n, vakavan masennuksen ja Touretten oireyhtymän kanssa. Riskivarianttien todellinen merkitys migreenin patofysiologiaan selviää vasta toiminnallisten tutkimusten avulla.
Published: 2021

20. Cerebral small vessel disease genomics and its implications across the lifespan

Author: International Headache Genomics Consortium (IHGC), International Network against Thrombosis (INVENT) Consortium, Sargurupremraj, Muralidharan, Suzuki, Hideaki, Anttila, Verneri, Palta, Priit, Muona, Mikko, Sarin, Antti-Pekka, Wedenoja, Juho, Färkkilä, Markus, Artto, Ville, Kaunisto, Mari, Vepsäläinen, Salli, Kurki, Mitja, Pärn, Kalle, Hämäläinen, Eija, Eriksson, Johan G., Heikkilä, Kauko, Kaprio, Jaakko, Wessman, Maija, Daly, Mark J., Neale, Benjamin M., Palotie, Aarno, Kallela, Mikko, Aarno Palotie / Principal Investigator, Genomics of Neurological and Neuropsychiatric Disorders, Institute for Molecular Medicine Finland, Research Programs Unit, Neuroscience Center, STEMM - Stem Cells and Metabolism Research Program, Clinicum, Department of Public Health, Neurologian yksikkö, HUS Neurocenter, HUS Helsinki and Uusimaa Hospital District, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, Helsinki University Hospital Area, University of Helsinki, Biosciences, Centre of Excellence in Complex Disease Genetics, and Department of Neurosciences
Subjects: mental disorders, behavioral disciplines and activities, 3124 Neurology and psychiatry
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.
Published: 2020

21. 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

22. 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

23. High-resolution population-specific recombination rates and their effect on phasing and genotype imputation

Author: Hassan, Shabbeer, primary, Surakka, Ida, additional, Taskinen, Marja-Riitta, additional, Salomaa, Veikko, additional, Palotie, Aarno, additional, Wessman, Maija, additional, Tukiainen, Taru, additional, Pirinen, Matti, additional, Palta, Priit, additional, and Ripatti, Samuli, additional
Published: 2020
Full Text: View/download PDF

24. Characterising the loss-of-function impact of 5’ untranslated region variants in whole genome sequence data from 15,708 individuals

Author: Whiffin, Nicola, Karczewski, Konrad J, Zhang, Xiaolei, Chothani, Sonia, Smith, Miriam J, Evans, D Gareth, Roberts, Angharad M, Quaife, Nicholas M, Schafer, Sebastian, Rackham, Owen, Alföldi, Jessica, O’Donnell-Luria, Anne H, Francioli, Laurent C, Armean, Irina M., Banks, Eric, Bergelson, Louis, Cibulskis, Kristian, Collins, Ryan L, Connolly, Kristen M., Covarrubias, Miguel, Cummings, Beryl, Daly, Mark J., Donnelly, Stacey, Farjoun, Yossi, Ferriera, Steven, Francioli, Laurent, Gabriel, Stacey, Gauthier, Laura D., Gentry, Jeff, Gupta, Namrata, Jeandet, Thibault, Kaplan, Diane, Karczewski, Konrad J., Laricchia, Kristen M., Llanwarne, Christopher, Minikel, Eric V., Munshi, Ruchi, Neale, Benjamin M, Novod, Sam, O’Donnell-Luria, Anne H., Petrillo, Nikelle, Poterba, Timothy, Roazen, David, Ruano-Rubio, Valentin, Saltzman, Andrea, Samocha, Kaitlin E., Schleicher, Molly, Seed, Cotton, Solomonson, Matthew, Soto, Jose, Tiao, Grace, Tibbetts, Kathleen, Tolonen, Charlotte, Vittal, Christopher, Wade, Gordon, Wang, Arcturus, Wang, Qingbo, Ware, James S, Watts, Nicholas A, Weisburd, Ben, Salinas, Carlos A Aguilar, Ahmad, Tariq, Albert, Christine M., Ardissino, Diego, Atzmon, Gil, Barnard, John, Beaugerie, Laurent, Benjamin, Emelia J., Boehnke, Michael, Bonnycastle, Lori L., Bottinger, Erwin P., Bowden, Donald W, Bown, Matthew J, Chambers, John C, Chan, Juliana C., Chasman, Daniel, Cho, Judy, Chung, Mina K., Cohen, Bruce, Correa, Adolfo, Dabelea, Dana, Darbar, Dawood, Duggirala, Ravindranath, Dupuis, Josée, Ellinor, Patrick T., Elosua, Roberto, Erdmann, Jeanette, Esko, Tõnu, Färkkilä, Martti, Florez, Jose, Franke, Andre, Getz, Gad, Glaser, Benjamin, Glatt, Stephen J., Goldstein, David, Gonzalez, Clicerio, Groop, Leif, Haiman, Christopher, Hanis, Craig, Harms, Matthew, Hiltunen, Mikko, Holi, Matti M., Hultman, Christina M., Kallela, Mikko, Kaprio, Jaakko, Kathiresan, Sekar, Kim, Bong-Jo, Kim, Young Jin, Kirov, George, Kooner, Jaspal, Koskinen, Seppo, Krumholz, Harlan M., Kugathasan, Subra, Kwak, Soo Heon, Laakso, Markku, Lehtimäki, Terho, Loos, Ruth J.F., Lubitz, Steven A., Ma, Ronald C.W., MacArthur, Daniel G., Marrugat, Jaume, Mattila, Kari M., McCarroll, Steven, McCarthy, Mark I, McGovern, Dermot, McPherson, Ruth, Meigs, James B., Melander, Olle, Metspalu, Andres, Nilsson, Peter M, O’Donovan, Michael C, Ongur, Dost, Orozco, Lorena, Owen, Michael J, Palmer, Colin N.A., Palotie, Aarno, Park, Kyong Soo, Pato, Carlos, Pulver, Ann E., Rahman, Nazneen, Remes, Anne M., Rioux, John D., Ripatti, Samuli, Roden, Dan M., Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Scharf, Jeremiah, Schunkert, Heribert, Shoemaker, Moore B., Sklar, Pamela, Soininen, Hilkka, Soko, Harry, Spector, Tim, Sullivan, Patrick F., Suvisaari, Jaana, Tai, E Shyong, Teo, Yik Ying, Tiinamaija, Tuomi, Tsuang, Ming, Turner, Dan, Tusie-Luna, Teresa, Vartiainen, Erkki, Watkins, Hugh, Weersma, Rinse K, Wessman, Maija, Wilson, James G., Xavier, Ramnik J., Cook, Stuart A, Barton, Paul J R, and MacArthur, Daniel G
Subjects: 0303 health sciences, education.field_of_study, Five prime untranslated region, Population, Computational biology, Biology, Genome, DNA sequencing, Frameshift mutation, 03 medical and health sciences, Negative selection, 0302 clinical medicine, Coding region, education, Gene, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract: Upstream open reading frames (uORFs) are important tissue-specific cis-regulators of protein translation. Although isolated case reports have shown that variants that create or disrupt uORFs can cause disease, genetic sequencing approaches typically focus on protein-coding regions and ignore these variants. Here, we describe a systematic genome-wide study of variants that create and disrupt human uORFs, and explore their role in human disease using 15,708 whole genome sequences collected by the Genome Aggregation Database (gnomAD) project. We show that 14,897 variants that create new start codons upstream of the canonical coding sequence (CDS), and 2,406 variants disrupting the stop site of existing uORFs, are under strong negative selection. Furthermore, variants creating uORFs that overlap the CDS show signals of selection equivalent to coding loss-of-function variants, and uORF-perturbing variants are under strong selection when arising upstream of known disease genes and genes intolerant to loss-of-function variants. Finally, we identify specific genes where perturbation of uORFs is likely to represent an important disease mechanism, and report a novel uORF frameshift variant upstream of NF2 in families with neurofibromatosis. Our results highlight uORF-perturbing variants as an important and under-recognised functional class that can contribute to penetrant human disease, and demonstrate the power of large-scale population sequencing data to study the deleteriousness of specific classes of non-coding variants.
Published: 2019
Full Text: View/download PDF

25. 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

26. Correction : Common variant burden contributes to the familial aggregation of migraine in 1,589 families

Author: Gormley, Padhraig, Kurki, Mitja, Hiekkala, Marjo Eveliina, Veerapen, Kumar, Häppölä, Paavo, Mitchell, Adele A., Lal, Dennis, Palta, Priit, Surakka, Ida, Hamalainen, Eija, Vepsäläinen, Salli, Havanka, Hannele, Harno, Hanna, Ilmavirta, Matti, Nissilä, Markku, Säkö, Erkki, Sumelahti, Marja Liisa, Liukkonen, Jarmo, Sillanpää, Matti, Metsähonkala, Liisa, Koskinen, Seppo, Lehtimäki, Terho, Raitakari, Olli, Männikkö, Minna, Ran, Caroline, Jousilahti, Pekka, Anttila, Verneri, Salomaa, Veikko, Artto, Ville, Färkkilä, Markus, Agee, Michelle, Alipanahi, Babak, Auton, Adam, Bell, Robert K., Bryc, Katarzyna, Elson, Sarah L., Fontanillas, Pierre, Furlotte, Nick, Huber, Karen E., Kleinman, Aaron, Litterman, Nadia, McCreight, Jennifer C., McIntyre, Matthew H., Mountain, Joanna L., Pitts, Steven J., Sathirapongsasuti, J. Fah, Sazonova, Olga V., Shelton, Janie F., Shringarpure, Suyash, Tian, Chao, Tung, Joyce Y., Vacic, Vladimir, Wilson, Catherine H., Belin, Andrea Carmine, 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 D., Frants, Rune R., Freilinger, Tobias, Griffiths, Lyn, Hansen, Thomas Folkmann, Ikram, M. Arfan, Ingason, Andres, Järvelin, Marjo Riitta, Kajanne, Risto, Kallela, Mikko, Kaprio, Jaakko, Kaunisto, Mari, Kubisch, Christian, Kurth, Tobias, Launer, Lenore, Lessel, Davor, Ligthart, Lannie, van den Maagdenberg, Arn, Macaya, Alfons, Malik, Rainer, Mangino, Massimo, McMahon, George, Muller-Myhsok, Bertram, Neale, Benjamin M., Northover, Carrie, Nyholt, Dale R., Olesen, Jes, Palotie, Aarno, Pedersen, Linda, Pedersen, Nancy, Posthuma, Danielle, Pozo-Rosich, Patricia, Pressman, Alice, Quaye, Lydia, Schürks, Markus, Sintas, Celia, Stefansson, Kari, Stefansson, Hreinn, Steinberg, Stacy, Strachan, David, Terwindt, Gisela, Vila-Pueyo, Marta, Wessman, Maija, Winsvold, Bendik S., Wrenthal, William, Zhao, Huiying, Zwart, John Anker, Runz, Heiko, Daly, Mark J., Ripatti, Samuli, Gormley, Padhraig, Kurki, Mitja, Hiekkala, Marjo Eveliina, Veerapen, Kumar, Häppölä, Paavo, Mitchell, Adele A., Lal, Dennis, Palta, Priit, Surakka, Ida, Hamalainen, Eija, Vepsäläinen, Salli, Havanka, Hannele, Harno, Hanna, Ilmavirta, Matti, Nissilä, Markku, Säkö, Erkki, Sumelahti, Marja Liisa, Liukkonen, Jarmo, Sillanpää, Matti, Metsähonkala, Liisa, Koskinen, Seppo, Lehtimäki, Terho, Raitakari, Olli, Männikkö, Minna, Ran, Caroline, Jousilahti, Pekka, Anttila, Verneri, Salomaa, Veikko, Artto, Ville, Färkkilä, Markus, Agee, Michelle, Alipanahi, Babak, Auton, Adam, Bell, Robert K., Bryc, Katarzyna, Elson, Sarah L., Fontanillas, Pierre, Furlotte, Nick, Huber, Karen E., Kleinman, Aaron, Litterman, Nadia, McCreight, Jennifer C., McIntyre, Matthew H., Mountain, Joanna L., Pitts, Steven J., Sathirapongsasuti, J. Fah, Sazonova, Olga V., Shelton, Janie F., Shringarpure, Suyash, Tian, Chao, Tung, Joyce Y., Vacic, Vladimir, Wilson, Catherine H., Belin, Andrea Carmine, 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 D., Frants, Rune R., Freilinger, Tobias, Griffiths, Lyn, Hansen, Thomas Folkmann, Ikram, M. Arfan, Ingason, Andres, Järvelin, Marjo Riitta, Kajanne, Risto, Kallela, Mikko, Kaprio, Jaakko, Kaunisto, Mari, Kubisch, Christian, Kurth, Tobias, Launer, Lenore, Lessel, Davor, Ligthart, Lannie, van den Maagdenberg, Arn, Macaya, Alfons, Malik, Rainer, Mangino, Massimo, McMahon, George, Muller-Myhsok, Bertram, Neale, Benjamin M., Northover, Carrie, Nyholt, Dale R., Olesen, Jes, Palotie, Aarno, Pedersen, Linda, Pedersen, Nancy, Posthuma, Danielle, Pozo-Rosich, Patricia, Pressman, Alice, Quaye, Lydia, Schürks, Markus, Sintas, Celia, Stefansson, Kari, Stefansson, Hreinn, Steinberg, Stacy, Strachan, David, Terwindt, Gisela, Vila-Pueyo, Marta, Wessman, Maija, Winsvold, Bendik S., Wrenthal, William, Zhao, Huiying, Zwart, John Anker, Runz, Heiko, Daly, Mark J., and Ripatti, Samuli
Abstract: (Neuron 98, 743–753.e1–e4; May 16, 2018) In the original publication of this paper, the middle initial of Michael D. Ferrari's name was inadvertently left out. This has since been corrected online. The authors apologize for the error.
Published: 2018

27. Common variant burden contributes to the familial aggregation of migraine in 1,589 families

Author: Gormley, Padhraig, Kurki, Mitja I., Hiekkala, Marjo Eveliina, Veerapen, Kumar, Häppölä, Paavo, Mitchell, Adele A., Lal, Dennis, Palta, Priit, Surakka, Ida, Kaunisto, Mari Anneli, Hamalainen, Eija, Vepsäläinen, Salli, Havanka, Hannele, Harno, Hanna, Ilmavirta, Matti, Nissilä, Markku, Säkö, Erkki, Sumelahti, Marja Liisa, Liukkonen, Jarmo, Sillanpää, Matti, Metsähonkala, Liisa, Koskinen, Seppo, Lehtimäki, Terho, Raitakari, Olli, Männikkö, Minna, Ran, Caroline, Belin, Andrea Carmine, Jousilahti, Pekka, Anttila, Verneri, Salomaa, Veikko, Artto, Ville, Färkkilä, Markus, Agee, Michelle, Alipanahi, Babak, Auton, Adam, Bell, Robert K., Bryc, Katarzyna, Elson, Sarah L., Fontanillas, Pierre, Furlotte, Nicholas A., Huber, Karen E., Kleinman, Aaron, Litterman, Nadia K., McCreight, Jennifer C., McIntyre, Matthew H., Mountain, Joanna L., 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, Wilson, Catherine H., 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, Griffiths, Lyn, Hansen, Thomas Folkmann, Ikram, M. Arfan, Ingason, Andres, Järvelin, Marjo Riitta, Kajanne, Risto, Kallela, Mikko, Kaprio, Jaakko, Kubisch, Christian, Kurth, Tobias, Launer, Lenore, Lessel, Davor, Ligthart, Lannie, van den Maagdenberg, Arn, Macaya, Alfons, Malik, Rainer, Mangino, Massimo, McMahon, George, Muller-Myhsok, Bertram, Neale, Benjamin M., Nyholt, Dale R., Olesen, Jes, Palotie, Aarno, Pedersen, Linda, Pedersen, Nancy, Posthuma, Danielle, Pozo-Rosich, Patricia, Pressman, Alice, Quaye, Lydia, Schürks, Markus, Sintas, Celia, Stefansson, Kari, Stefansson, Hreinn, Steinberg, Stacy, Strachan, David, Terwindt, Gisela, Vila-Pueyo, Marta, Wessman, Maija, Winsvold, Bendik S., Wrenthal, William, Zhao, Huiying, Zwart, John Anker, Runz, Heiko, Daly, Mark J., Ripatti, Samuli, Gormley, Padhraig, Kurki, Mitja I., Hiekkala, Marjo Eveliina, Veerapen, Kumar, Häppölä, Paavo, Mitchell, Adele A., Lal, Dennis, Palta, Priit, Surakka, Ida, Kaunisto, Mari Anneli, Hamalainen, Eija, Vepsäläinen, Salli, Havanka, Hannele, Harno, Hanna, Ilmavirta, Matti, Nissilä, Markku, Säkö, Erkki, Sumelahti, Marja Liisa, Liukkonen, Jarmo, Sillanpää, Matti, Metsähonkala, Liisa, Koskinen, Seppo, Lehtimäki, Terho, Raitakari, Olli, Männikkö, Minna, Ran, Caroline, Belin, Andrea Carmine, Jousilahti, Pekka, Anttila, Verneri, Salomaa, Veikko, Artto, Ville, Färkkilä, Markus, Agee, Michelle, Alipanahi, Babak, Auton, Adam, Bell, Robert K., Bryc, Katarzyna, Elson, Sarah L., Fontanillas, Pierre, Furlotte, Nicholas A., Huber, Karen E., Kleinman, Aaron, Litterman, Nadia K., McCreight, Jennifer C., McIntyre, Matthew H., Mountain, Joanna L., 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, Wilson, Catherine H., 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, Griffiths, Lyn, Hansen, Thomas Folkmann, Ikram, M. Arfan, Ingason, Andres, Järvelin, Marjo Riitta, Kajanne, Risto, Kallela, Mikko, Kaprio, Jaakko, Kubisch, Christian, Kurth, Tobias, Launer, Lenore, Lessel, Davor, Ligthart, Lannie, van den Maagdenberg, Arn, Macaya, Alfons, Malik, Rainer, Mangino, Massimo, McMahon, George, Muller-Myhsok, Bertram, Neale, Benjamin M., Nyholt, Dale R., Olesen, Jes, Palotie, Aarno, Pedersen, Linda, Pedersen, Nancy, Posthuma, Danielle, Pozo-Rosich, Patricia, Pressman, Alice, Quaye, Lydia, Schürks, Markus, Sintas, Celia, Stefansson, Kari, Stefansson, Hreinn, Steinberg, Stacy, Strachan, David, Terwindt, Gisela, Vila-Pueyo, Marta, Wessman, Maija, Winsvold, Bendik S., Wrenthal, William, Zhao, Huiying, Zwart, John Anker, Runz, Heiko, Daly, Mark J., and Ripatti, Samuli
Abstract: Complex traits, including migraine, often aggregate in families, but the underlying genetic architecture behind this is not well understood. The aggregation could be explained by rare, penetrant variants that segregate according to Mendelian inheritance or by the sufficient polygenic accumulation of common variants, each with an individually small effect, or a combination of the two hypotheses. In 8,319 individuals across 1,589 migraine families, we calculated migraine polygenic risk scores (PRS) and found a significantly higher common variant burden in familial cases (n = 5,317, OR = 1.76, 95% CI = 1.71–1.81, p = 1.7 × 10−109) compared to population cases from the FINRISK cohort (n = 1,101, OR = 1.32, 95% CI = 1.25–1.38, p = 7.2 × 10−17). The PRS explained 1.6% of the phenotypic variance in the population cases and 3.5% in the familial cases (including 2.9% for migraine without aura, 5.5% for migraine with typical aura, and 8.2% for hemiplegic migraine). The results demonstrate a significant contribution of common polygenic variation to the familial aggregation of migraine. Gormley et al. use polygenic risk scores to show that common variation, captured by genome-wide association studies, in combination contributes to the aggregation of migraine in families. The results may have similar implications for other complex traits in general.
Published: 2018

28. The contribution of CACNA1A, ATP1A2 and SCN1A mutations in hemiplegic migraine: A clinical and genetic study in Finnish migraine families

Author: Hiekkala, Marjo Eveliina, Vuola, Pietari, Artto, Ville, Happola, Paavo, Happola, Elisa, Vepsalainen, Salli, Cuenca-Leon, Ester, Lal, Dennis, Gormley, Padhraig, Hamalainen, Eija, Ilmavirta, Matti, Nissila, Markku, Sako, Erkki, Sumelahti, Marja-Liisa, Harno, Hanna, Havanka, Hannele, Keski-Santti, Petra, Farkkila, Markus, Palotie, Aarno, Wessman, Maija, Kaunisto, Mari Anneli, Kallela, Mikko, Hiekkala, Marjo Eveliina, Vuola, Pietari, Artto, Ville, Happola, Paavo, Happola, Elisa, Vepsalainen, Salli, Cuenca-Leon, Ester, Lal, Dennis, Gormley, Padhraig, Hamalainen, Eija, Ilmavirta, Matti, Nissila, Markku, Sako, Erkki, Sumelahti, Marja-Liisa, Harno, Hanna, Havanka, Hannele, Keski-Santti, Petra, Farkkila, Markus, Palotie, Aarno, Wessman, Maija, Kaunisto, Mari Anneli, and Kallela, Mikko
Abstract: Objective To study the position of hemiplegic migraine in the clinical spectrum of migraine with aura and to reveal the importance of CACNA1A, ATP1A2 and SCN1A in the development of hemiplegic migraine in Finnish migraine families. Methods The International Classification of Headache Disorders 3rd edition criteria were used to determine clinical characteristics and occurrence of hemiplegic migraine, based on detailed questionnaires, in a Finnish migraine family collection consisting of 9087 subjects. Involvement of CACNA1A, ATP1A2 and SCN1A was studied using whole exome sequencing data from 293 patients with hemiplegic migraine. Results Overall, hemiplegic migraine patients reported clinically more severe headache and aura episodes than non-hemiplegic migraine with aura patients. We identified two mutations, c.1816G>A (p.Ala606Thr) and c.1148G>A (p.Arg383His), in ATP1A2 and one mutation, c.1994C>T (p.Thr665Met) in CACNA1A. Conclusions The results highlight hemiplegic migraine as a clinically and genetically heterogeneous disease. Hemiplegic migraine patients do not form a clearly separate group with distinct symptoms, but rather have an extreme phenotype in the migraine with aura continuum. We have shown that mutations in CACNA1A, ATP1A2 and SCN1A are not the major cause of the disease in Finnish hemiplegic migraine patients, suggesting that there are additional genetic factors contributing to the phenotype.
Published: 2018

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

Author: Kogelman, Lisette JA, 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, Soren, Buil, Alfonso, Burgdorf, Kristoffer, Gregor, Jemec, Jennum, Poul, Nielsen, Kasper Rene, Nyegaard, Mette, Paarup, Helene Mariana, Pedersen, Ole Birger, Sorensen, 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, Consortium, DBDS Genomic, Consortium, Int Headache Genetics, Neurologian yksikkö, HUS Helsinki and Uusimaa Hospital District, HUS Neurocenter, Institute for Molecular Medicine Finland, Genomics of Neurological and Neuropsychiatric Disorders, University of Helsinki, Centre of Excellence in Complex Disease Genetics, Research Programs Unit, and Aarno Palotie / Principal Investigator
Subjects: 0301 basic medicine, medicine.medical_specialty, SUSCEPTIBILITY LOCI, PHARMACOGENOMICS, Triptans, Logistic regression, Article, 3124 Neurology and psychiatry, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, SCHIZOPHRENIA, Medicine, Migraine treatment, METAANALYSIS, Genetics (clinical), business.industry, 1184 Genetics, developmental biology, physiology, 3112 Neurosciences, Area under the curve, Odds ratio, medicine.disease, Confidence interval, 3. Good health, 030104 developmental biology, Migraine, Cohort, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug
Abstract: ObjectiveTo assess whether the polygenic risk score (PRS) for migraine is associated with acute and/or prophylactic migraine treatment response.MethodsWe interviewed 2,219 unrelated patients at the Danish Headache Center using a semistructured interview to diagnose migraine and assess acute and prophylactic drug response. All patients were genotyped. A PRS was calculated with the linkage disequilibrium pred algorithm using summary statistics from the most recent migraine genome-wide association study comprising ∼375,000 cases and controls. The PRS was scaled to a unit corresponding to a twofold increase in migraine risk, using 929 unrelated Danish controls as reference. The association of the PRS with treatment response was assessed by logistic regression, and the predictive power of the model by area under the curve using a case-control design with treatment response as outcome.ResultsA twofold increase in migraine risk associates with positive response to migraine-specific acute treatment (odds ratio [OR] = 1.25 [95% confidence interval (CI) = 1.05–1.49]). The association between migraine risk and migraine-specific acute treatment was replicated in an independent cohort consisting of 5,616 triptan users with prescription history (OR = 3.20 [95% CI = 1.26–8.14]). No association was found for acute treatment with non–migraine-specific weak analgesics and prophylactic treatment response.ConclusionsThe migraine PRS can significantly identify subgroups of patients with a higher-than-average likelihood of a positive response to triptans, which provides a first step toward genetics-based precision medicine in migraine.
Published: 2019

30. Common Variant Burden Contributes to the Familial Aggregation of Migraine in 1,589 Families

Author: Gormley, Padhraig, primary, Kurki, Mitja I., additional, Hiekkala, Marjo Eveliina, additional, Veerapen, Kumar, additional, Häppölä, Paavo, additional, Mitchell, Adele A., additional, Lal, Dennis, additional, Palta, Priit, additional, Surakka, Ida, additional, Kaunisto, Mari Anneli, additional, Hämäläinen, Eija, additional, Vepsäläinen, Salli, additional, Havanka, Hannele, additional, Harno, Hanna, additional, Ilmavirta, Matti, additional, Nissilä, Markku, additional, Säkö, Erkki, additional, Sumelahti, Marja-Liisa, additional, Liukkonen, Jarmo, additional, Sillanpää, Matti, additional, Metsähonkala, Liisa, additional, Koskinen, Seppo, additional, Lehtimäki, Terho, additional, Raitakari, Olli, additional, Männikkö, Minna, additional, Ran, Caroline, additional, Belin, Andrea Carmine, additional, Jousilahti, Pekka, additional, Anttila, Verneri, additional, Salomaa, Veikko, additional, Artto, Ville, additional, Färkkilä, Markus, additional, Runz, Heiko, additional, Daly, Mark J., additional, Neale, Benjamin M., additional, Ripatti, Samuli, additional, Kallela, Mikko, additional, Wessman, Maija, additional, Palotie, Aarno, additional, Agee, Michelle, additional, Alipanahi, Babak, additional, Auton, Adam, additional, Bell, Robert K., additional, Bryc, Katarzyna, additional, Elson, Sarah L., additional, Fontanillas, Pierre, additional, Furlotte, Nicholas A., additional, Huber, Karen E., additional, Kleinman, Aaron, additional, Litterman, Nadia K., additional, McCreight, Jennifer C., additional, McIntyre, Matthew H., additional, Mountain, Joanna L., additional, Northover, Carrie A.M., additional, Pitts, Steven J., additional, Sathirapongsasuti, J. Fah, additional, Sazonova, Olga V., additional, Shelton, Janie F., additional, Shringarpure, Suyash, additional, Tian, Chao, additional, Tung, Joyce Y., additional, Vacic, Vladimir, additional, Wilson, Catherine H., additional, Boomsma, Dorret I., additional, Børte, Sigrid, additional, Chasman, Daniel I., additional, Cherkas, Lynn, additional, Christensen, Anne Francke, additional, Cormand, Bru, additional, Cuenca-Leon, Ester, additional, Davey-Smith, George, additional, Dichgans, Martin, additional, van Duijn, Cornelia, additional, Esko, Tonu, additional, Esserlind, Ann-Louise, additional, Ferrari, Michel D., additional, Frants, Rune R., additional, Freilinger, Tobias, additional, Furlotte, Nick, additional, Gormley, Padhraig, additional, Griffiths, Lyn, additional, Hamalainen, Eija, additional, Hansen, Thomas Folkmann, additional, Hiekkala, Marjo, additional, Ikram, M Arfan, additional, Ingason, Andres, additional, Järvelin, Marjo-Riitta, additional, Kajanne, Risto, additional, Kaprio, Jaakko, additional, Kaunisto, Mari, additional, Kubisch, Christian, additional, Kurki, Mitja, additional, Kurth, Tobias, additional, Launer, Lenore, additional, Lehtimaki, Terho, additional, Lessel, Davor, additional, Ligthart, Lannie, additional, Litterman, Nadia, additional, van den Maagdenberg, Arn, additional, Macaya, Alfons, additional, Malik, Rainer, additional, Mangino, Massimo, additional, McMahon, George, additional, Muller-Myhsok, Bertram, additional, Northover, Carrie, additional, Nyholt, Dale R., additional, Olesen, Jes, additional, Pedersen, Linda, additional, Pedersen, Nancy, additional, Posthuma, Danielle, additional, Pozo-Rosich, Patricia, additional, Pressman, Alice, additional, Quaye, Lydia, additional, Schürks, Markus, additional, Sintas, Celia, additional, Stefansson, Kari, additional, Stefansson, Hreinn, additional, Steinberg, Stacy, additional, Strachan, David, additional, Terwindt, Gisela, additional, Vila-Pueyo, Marta, additional, Winsvold, Bendik S., additional, Wrenthal, William, additional, Zhao, Huiying, additional, and Zwart, John-Anker, additional
Published: 2018
Full Text: View/download PDF

31. The contribution of CACNA1A, ATP1A2 and SCN1A mutations in hemiplegic migraine: A clinical and genetic study in Finnish migraine families

Author: Hiekkala, Marjo Eveliina, primary, Vuola, Pietari, additional, Artto, Ville, additional, Häppölä, Paavo, additional, Häppölä, Elisa, additional, Vepsäläinen, Salli, additional, Cuenca-León, Ester, additional, Lal, Dennis, additional, Gormley, Padhraig, additional, Hämäläinen, Eija, additional, Ilmavirta, Matti, additional, Nissilä, Markku, additional, Säkö, Erkki, additional, Sumelahti, Marja-Liisa, additional, Harno, Hanna, additional, Havanka, Hannele, additional, Keski-Säntti, Petra, additional, Färkkilä, Markus, additional, Palotie, Aarno, additional, Wessman, Maija, additional, Kaunisto, Mari Anneli, additional, and Kallela, Mikko, additional
Published: 2018
Full Text: View/download PDF

32. Premonitory symptoms in migraine : a cross-sectional study in 2714 persons

Author: Laurell, Katarina, Artto, Ville, Bendtsen, Lars, Hagen, Knut, Häggström, Johan, Linde, Mattias, Söderström, Lars, Tronvik, Erling, Wessman, Maija, Zwart, John Anker, Kallela, Mikko, Laurell, Katarina, Artto, Ville, Bendtsen, Lars, Hagen, Knut, Häggström, Johan, Linde, Mattias, Söderström, Lars, Tronvik, Erling, Wessman, Maija, Zwart, John Anker, and Kallela, Mikko
Abstract: AIM: To describe the frequency and number of premonitory symptoms (PS) in migraine, the co-occurrence of different PS, and their association with migraine-related factors. METHODS: In this cross-sectional study, a validated questionnaire was sent to Finnish migraine families between 2002 and 2013 to obtain data on 14 predefined PS, migraine diagnoses, demographic factors, and migraine characteristics. The estimated response rate was 80%. RESULTS: Out of 2714 persons, 2223 were diagnosed with migraine. Among these, 77% reported PS, with a mean number of 3.0 symptoms compared to 30% (p < 0.001) and 0.5 symptoms (p < 0.001) among 491 persons with non-migraine headaches. Yawning was the most commonly reported symptom (34%) among migraineurs. Females reported PS more frequently than males (81 versus 64%, p < 0.001) and experienced a higher number of different symptoms (mean 3.3 versus 1.8, p < 0.001). All measures of migraine severity were associated with a higher burden of PS. Light and sound sensitivity showed the highest co-occurrence (kappa = 0.51, 95% CI 0.47-0.55). In a generalized linear model, age, gender, higher frequency, duration and intensity of headache, reduced working capacity, most aura symptoms, and associated symptoms of the headache phase were significantly associated with an increased in the number of PS. CONCLUSION: PS are experienced by a majority of migraineurs. More severe migraine is associated with a higher burden of PS. Since the material was not entirely representative of the general population of migraineurs, caution should be exercised in generalizing the results.
Published: 2016
Full Text: View/download PDF

33. Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine

Author: 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, Hamalainen, 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, 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, Belin, Andrea Carmine, Dichgans, Martin, Wessman, Maija, van den Maagdenberg, Arn M.J.M., 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, Børte, Sigrid, Cormand, Bru, Eising, Else, Frants, Rune R., Griffiths, Lyn, Hiekkala, Marjo, Kajanne, Risto, Launer, Lenore, Lehtimaki, Terho, Lessel, Davor, Litterman, Nadia, Macaya, Alfons, Mangino, Massimo, Northover, Carrie, Pedersen, Nancy, Posthuma, Danielle, Pozo-Rosich, Patricia, Pressman, Alice, Sintas, Celia, Strachan, David, Vila-Pueyo, Marta, Wrenthal, William, Zhao, Huiying, other, and, 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, Hamalainen, 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, 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, Belin, Andrea Carmine, Dichgans, Martin, Wessman, Maija, van den Maagdenberg, Arn M.J.M., 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, Børte, Sigrid, Cormand, Bru, Eising, Else, Frants, Rune R., Griffiths, Lyn, Hiekkala, Marjo, Kajanne, Risto, Launer, Lenore, Lehtimaki, Terho, Lessel, Davor, Litterman, Nadia, Macaya, Alfons, Mangino, Massimo, Northover, Carrie, Pedersen, Nancy, Posthuma, Danielle, Pozo-Rosich, Patricia, Pressman, Alice, Sintas, Celia, Strachan, David, Vila-Pueyo, Marta, Wrenthal, William, Zhao, Huiying, and other, and
Abstract: Migraine is a debilitating neurological disorder affecting around one in seven people worldwide, but its molecular mechanisms remain poorly understood. There is some debate about whether migraine is a disease of vascular dysfunction or a result of neuronal dysfunction with secondary vascular changes. Genome-wide association (GWA) studies have thus far identified 13 independent loci associated with migraine. To identify new susceptibility loci, we carried out a genetic study of migraine on 59,674 affected subjects and 316,078 controls from 22 GWA studies. We identified 44 independent single-nucleotide polymorphisms (SNPs) significantly associated with migraine risk (P < 5 × 10-8) that mapped to 38 distinct genomic loci, including 28 loci not previously reported and a locus that to our knowledge is the first to be identified on chromosome X. In subsequent computational analyses, the identified loci showed enrichment for genes expressed in vascular and smooth muscle tissues, consistent with a predominant theory of migraine that highlights vascular etiologies.
Published: 2016

34. Premonitory symptoms in migraine:A cross-sectional study in 2714 persons

Author: Laurell, Katarina, Artto, Ville, Bendtsen, Lars, Hagen, Knut, Häggström, Johan, Linde, Mattias, Söderström, Lars, Tronvik, Erling, Wessman, Maija, Zwart, John Anker, Kallela, Mikko, Laurell, Katarina, Artto, Ville, Bendtsen, Lars, Hagen, Knut, Häggström, Johan, Linde, Mattias, Söderström, Lars, Tronvik, Erling, Wessman, Maija, Zwart, John Anker, and Kallela, Mikko
Abstract: AIM: To describe the frequency and number of premonitory symptoms (PS) in migraine, the co-occurrence of different PS, and their association with migraine-related factors.METHODS: In this cross-sectional study, a validated questionnaire was sent to Finnish migraine families between 2002 and 2013 to obtain data on 14 predefined PS, migraine diagnoses, demographic factors, and migraine characteristics. The estimated response rate was 80%.RESULTS: Out of 2714 persons, 2223 were diagnosed with migraine. Among these, 77% reported PS, with a mean number of 3.0 symptoms compared to 30% (p < 0.001) and 0.5 symptoms (p < 0.001) among 491 persons with non-migraine headaches. Yawning was the most commonly reported symptom (34%) among migraineurs. Females reported PS more frequently than males (81 versus 64%, p < 0.001) and experienced a higher number of different symptoms (mean 3.3 versus 1.8, p < 0.001). All measures of migraine severity were associated with a higher burden of PS. Light and sound sensitivity showed the highest co-occurrence (kappa = 0.51, 95% CI 0.47-0.55). In a generalized linear model, age, gender, higher frequency, duration and intensity of headache, reduced working capacity, most aura symptoms, and associated symptoms of the headache phase were significantly associated with an increased in the number of PS.CONCLUSION: PS are experienced by a majority of migraineurs. More severe migraine is associated with a higher burden of PS. Since the material was not entirely representative of the general population of migraineurs, caution should be exercised in generalizing the results.
Published: 2016

35. Premonitory symptoms in migraine: A cross-sectional study in 2714 persons

Author: Laurell, Katarina, primary, Artto, Ville, additional, Bendtsen, Lars, additional, Hagen, Knut, additional, Häggström, Johan, additional, Linde, Mattias, additional, Söderström, Lars, additional, Tronvik, Erling, additional, Wessman, Maija, additional, Zwart, John Anker, additional, and Kallela, Mikko, additional
Published: 2016
Full Text: View/download PDF

36. Effect of endocannabinoid degradation on pain

Author: Cajanus, Kristiina, primary, Holmström, Emil J., additional, Wessman, Maija, additional, Anttila, Verneri, additional, Kaunisto, Mari A., additional, and Kalso, Eija, additional
Published: 2016
Full Text: View/download PDF

37. Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine

Author: Gormley, Padhraig, primary, Anttila, Verneri, additional, Winsvold, Bendik S, additional, Palta, Priit, additional, Esko, Tonu, additional, Pers, Tune H, additional, Farh, Kai-How, additional, Cuenca-Leon, Ester, additional, Muona, Mikko, additional, Furlotte, Nicholas A, additional, Kurth, Tobias, additional, Ingason, Andres, additional, McMahon, George, additional, Ligthart, Lannie, additional, Terwindt, Gisela M, additional, Kallela, Mikko, additional, Freilinger, Tobias M, additional, Ran, Caroline, additional, Gordon, Scott G, additional, Stam, Anine H, additional, Steinberg, Stacy, additional, Borck, Guntram, additional, Koiranen, Markku, additional, Quaye, Lydia, additional, Adams, Hieab HH, additional, Lehtimaki, Terho, additional, Sarin, Antti-Pekka, additional, Wedenoja, Juho, additional, Hinds, David A, additional, Buring, Julie E, additional, Schurks, Markus, additional, Ridker, Paul M, additional, Hrafnsdottir, Maria Gudlaug, additional, Stefansson, Hreinn, additional, Ring, Susan M, additional, Hottenga, Jouke-Jan, additional, Penninx, Brenda WJH, additional, Farkkila, Markus, additional, Artto, Ville, additional, Kaunisto, Mari, additional, Vepsalainen, Salli, additional, Malik, Rainer, additional, Heath, Andrew C, additional, Madden, Pamela AF, additional, Martin, Nicholas G, additional, Montgomery, Grant W, additional, Hamalainen, Eija, additional, Huang, Hailiang, additional, Byrnes, Andrea E, additional, Franke, Lude, additional, Huang, Jie, additional, Stergiakouli, Evie, additional, Lee, Phil H, additional, Sandor, Cynthia, additional, Webber, Caleb, additional, Cader, Zameel, additional, Muller-Myhsok, Bertram, additional, Schreiber, Stefan, additional, Meitinger, Thomas, additional, Eriksson, Johan G, additional, Salomaa, Veikko, additional, Heikkila, Kauko, additional, Loehrer, Elizabeth, additional, Uitterlinden, Andre G, additional, Hofman, Albert, additional, van Duijn, Cornelia M, additional, Cherkas, Lynn, additional, Pedersen, Linda M, additional, Stubhaug, Audun, additional, Nielsen, Christopher S, additional, Mannikko, Minna, additional, Mihailov, Evelin, additional, Milani, Lili, additional, Gobel, Hartmut, additional, Esserlind, Ann-Louise, additional, Christensen, Anne Francke, additional, Hansen, Thomas Folkmann, additional, Werge, Thomas, additional, Kaprio, Jaakko, additional, Aromaa, Arpo J, additional, Raitakari, Olli, additional, Ikram, M Arfan, additional, Spector, Tim, additional, Jarvelin, Marjo-Riitta, additional, Metspalu, Andres, additional, Kubisch, Christian, additional, Strachan, David P, additional, Ferrari, Michel D, additional, Belin, Andrea C, additional, Dichgans, Martin, additional, Wessman, Maija, additional, van den Maagdenberg, Arn MJM, additional, Zwart, John-Anker, additional, Boomsma, Dorret I, additional, Smith, George Davey, additional, Stefansson, Kari, additional, Eriksson, Nicholas, additional, Daly, Mark J, additional, Neale, Benjamin M, additional, Olesen, Jes, additional, Chasman, Daniel I, additional, Nyholt, Dale R, additional, and Palotie, Aarno, additional
Published: 2015
Full Text: View/download PDF

38. A Novel Splice Mutation inPLS3Causes X-linked Early Onset Low-Turnover Osteoporosis

Author: Laine, Christine M, primary, Wessman, Maija, additional, Toiviainen-Salo, Sanna, additional, Kaunisto, Mari A, additional, Mäyränpää, Mervi K, additional, Laine, Tero, additional, Pekkinen, Minna, additional, Kröger, Heikki, additional, Välimäki, Ville-Valtteri, additional, Välimäki, Matti J, additional, Lehesjoki, Anna-Elina, additional, and Mäkitie, Outi, additional
Published: 2015
Full Text: View/download PDF

39. Genome wide association study identifies variants in NBEA associated with migraine in bipolar disorder

Author: Jacobsen, Kaya K., primary, Nievergelt, Caroline M., additional, Zayats, Tetyana, additional, Greenwood, Tiffany A., additional, Anttila, Verneri, additional, Akiskal, Hagop S., additional, Haavik, Jan, additional, Bernt Fasmer, Ole, additional, Kelsoe, John R., additional, Johansson, Stefan, additional, Oedegaard, Ketil J., additional, McKinney, Rebecca, additional, Shilling, Paul D., additional, Smith, Erin N., additional, Schork, Nicholas J., additional, Bloss, Cinnamon S., additional, Nurnberger, John I., additional, Edenberg, Howard J., additional, Foroud, Tatiana, additional, Koller, Daniel L., additional, Gershon, Elliot S., additional, Badner, Judith A., additional, Liu, Chunyu, additional, Scheftner, William A., additional, Lawson, William B., additional, Nwulia, Evaristus A., additional, Hipolito, Maria, additional, Potash, James, additional, Coryell, William, additional, Rice, John, additional, Byerley, William, additional, McMahon, Francis J., additional, Berrettini, Wade H., additional, Zandi, Peter P., additional, Mahon, Pamela B., additional, McInnis, Melvin G., additional, Zöllner, Sebastian, additional, Zhang, Peng, additional, Craig, David W., additional, Szelinger, Szabolics, additional, Barrett, Thomas B., additional, Schulze, Thomas G., additional, Wedenoja, Juho, additional, Kaunisto, Mari A., additional, Heikkilä, Kauko, additional, Kaprio, Jaakko, additional, Wessman, Maija, additional, Kallela, Mikko, additional, Färkkilä, Markus, additional, Artto, Ville, additional, Aromaa, Arpo, additional, Eriksson, Johan G., additional, Winsvold, Bendik S., additional, Zwart, John-Anker, additional, Gormley, Padhraig, additional, Palotie, Aarno, additional, Kurth, Tobias, additional, Rose, Lynda M., additional, Buring, Julie E., additional, Ridker, Paul M., additional, Chasman, Daniel I., additional, Bettella, Francesco, additional, Steinberg, Stacy, additional, Stefansson, Hreinn, additional, Stefansson, Kari, additional, McMahon, George, additional, Davey-Smith, George, additional, Malik, Rainer, additional, Freilinger, Tobias, additional, Erich Wichmann, Heinz, additional, Dichgans, Martin, additional, Muller-Myhsok, Bertram, additional, Meitinger, Thomas, additional, de Vries, Boukje, additional, Terwindt, Gisela, additional, Stam, Anine H., additional, Frants, Rune R., additional, Pelzer, Nadine, additional, Weller, Claudia M., additional, Zielman, Ronald, additional, Ferrari, Michel D., additional, van den Maagdenberg, Arn M.J.M., additional, Medland, Sarah E., additional, Montgomery, Grant W., additional, Martin, Nicholas G., additional, Nyholt, Dale R., additional, Todt, Unda, additional, Borck, Guntram, additional, Kubisch, Christian, additional, Quaye, Lydia, additional, Williams, Frances M.K., additional, Cherkas, Lynn, additional, Koiranen, Markku, additional, Hartikainen, Anna-Liisa, additional, Pouta, Anneli, additional, Jarvelin, Marjo-Riitta, additional, Arfan Ikram, M., additional, van den Ende, Joyce, additional, Uitterlinden, Andre G., additional, Hofman, Albert, additional, Amin, Najaf, additional, van Duijn, Cornelia, additional, Lehtimäki, Terho, additional, Ligthart, Lannie, additional, Hottenga, Jouke-Jan, additional, Vink, Jacqueline M., additional, Penninx, Brenda W., additional, Boomsma, Dorret I., additional, Schürks, Markus, additional, Jakobsson, Finnbogi, additional, Schoenen, Jean, additional, Heath, Andrew C., additional, Madden, Pamela A.F., additional, Göbel, Hartmut, additional, Heinze, Axel, additional, Heinze-Kuhn, Katja, additional, Schreiber, Stefan, additional, Daly, Mark J., additional, Alexander, Michael, additional, Raitakari, Olli, additional, and Strachan, David P., additional
Published: 2015
Full Text: View/download PDF

40. Systematic re-evaluation of genes from candidate gene association studies in migraine using a large genome-wide association data set

Author: de Vries, Boukje, primary, Anttila, Verneri, additional, Freilinger, Tobias, additional, Wessman, Maija, additional, Kaunisto, Mari A, additional, Kallela, Mikko, additional, Artto, Ville, additional, Vijfhuizen, Lisanne S, additional, Göbel, Hartmut, additional, Dichgans, Martin, additional, Kubisch, Christian, additional, Ferrari, Michel D, additional, Palotie, Aarno, additional, Terwindt, Gisela M, additional, and van den Maagdenberg, Arn MJM, additional
Published: 2015
Full Text: View/download PDF

41. Genetic analysis for a shared biological basis between migraine and coronary artery disease

Author: Winsvold, Bendik S., Nelson, Christopher P., Malik, Rainer, Gormley, Padhraig, Anttila, Verneri, Heiden, Jason Vander, Elliott, Katherine S., Jacobsen, Line M., Palta, Priit, Amin, Najaf, De Vries, Boukje, Hämäläinen, Eija, Freilinger, Tobias, Ikram, M. Arfan, Kessler, Thorsten, Koiranen, Markku, Ligthart, Lannie, McMahon, George, Pedersen, Linda M., Willenborg, Christina, Won, Hong-Hee, Olesen, Jes, Artto, Ville, Assimes, Themistocles L., Blankenberg, Stefan, Boomsma, Dorret I., Cherkas, Lynn, Smith, George Davey, Epstein, Stephen E., Erdmann, Jeanette, Ferrari, Michel D., Göbel, Hartmut, Hall, Alistair S., Jarvelin, Marjo-Riitta, Kallela, Mikko, Kaprio, Jaakko, Kathiresan, Sekar, Lehtimäki, Terho, McPherson, Ruth, März, Winfried, Nyholt, Dale R., O'Donnell, Christopher J., Quaye, Lydia, Rader, Daniel J., Raitakari, Olli, Roberts, Robert, Schunkert, Heribert, Schürks, Markus, Stewart, Alexandre F.R., Terwindt, Gisela M., Thorsteinsdottir, Unnur, Van Den Maagdenberg, Arn M.J.M., Van Duijn, Cornelia, Wessman, Maija, Kurth, Tobias, Kubisch, Christian, Dichgans, Martin, Chasman, Daniel I., Cotsapas, Chris, Zwart, John-Anker, Samani, Nilesh J., Palotie, Aarno, Vander Heiden, Jason, and Davey Smith, George
Subjects: Aura, Medizin, CAD, Bioinformatics, Genetic analysis, Article, Coronary artery disease, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, medicine, Endothelial dysfunction, Genetics (clinical), 030304 developmental biology, Genetic association, 0303 health sciences, business.industry, ta1184, ta3121, medicine.disease, 3. Good health, Migraine, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Objective: To apply genetic analysis of genome-wide association data to study the extent and nature of a shared biological basis between migraine and coronary artery disease (CAD). Methods: Four separate methods for cross-phenotype genetic analysis were applied on data from 2 large-scale genome-wide association studies of migraine (19,981 cases, 56,667 controls) and CAD (21,076 cases, 63,014 controls). The first 2 methods quantified the extent of overlapping risk variants and assessed the load of CAD risk loci in migraineurs. Genomic regions of shared risk were then identified by analysis of covariance patterns between the 2 phenotypes and by querying known genome-wide significant loci. Results: We found a significant overlap of genetic risk loci for migraine and CAD. When stratified by migraine subtype, this was limited to migraine without aura, and the overlap was protective in that patients with migraine had a lower load of CAD risk alleles than controls. Genes indicated by 16 shared risk loci point to mechanisms with potential roles in migraine pathogenesis and CAD, including endothelial dysfunction (PHACTR1) and insulin homeostasis (GIP). Conclusions: The results suggest that shared biological processes contribute to risk of migraine and CAD, but surprisingly this commonality is restricted to migraine without aura and the impact is in opposite directions. Understanding the mechanisms underlying these processes and their opposite relationship to migraine and CAD may improve our understanding of both disorders. CA extern
Published: 2015

42. Shared genetic basis for migraine and ischemic stroke: A genome-wide analysis of common variants.

Author: Malik, Rainer, Freilinger, Tobias, Winsvold, Bendik S, Anttila, Verneri, Vander Heiden, Jason, Traylor, Matthew, de Vries, Boukje, Holliday, Elizabeth G, Terwindt, Gisela M, Sturm, Jonathan, Bis, Joshua C, Hopewell, Jemma C, Ferrari, Michel D, Rannikmae, Kristiina, Wessman, Maija, Kallela, Mikko, Kubisch, Christian, Fornage, Myriam, Meschia, James F, and Lehtimäki, Terho
Published: 2015
Full Text: View/download PDF

43. A Novel Splice Mutation in PLS3 Causes X-linked Early Onset Low-Turnover Osteoporosis.

Author: Pekkinen, Minna, Lehesjoki, Anna-Elina, Laine, Christine M, Wessman, Maija, Kaunisto, Mari A, Mäkitie, Outi, Toiviainen-Salo, Sanna, Mäyränpää, Mervi K, Laine, Tero, Kröger, Heikki, Välimäki, Ville-Valtteri, and Välimäki, Matti J
Abstract: ABSTRACT Genetic factors play an important role in the development of osteoporosis. Several monogenic forms of osteoporosis have been recognized, most recently an X-chromosomal form resulting from mutations in the gene encoding plastin 3 ( PLS3). PLS3 is a protein involved in actin bundle formation in the cytoskeleton. We present a large family with early onset osteoporosis and X-linked inheritance. Phenotyping was performed on 19 family members and whole-exome sequencing on 7 family members (5 with a diagnosis of early onset osteoporosis and 2 with normal bone parameters). Osteoporosis had its onset in childhood and was characterized by recurrent peripheral fractures, low bone mineral density (BMD), vertebral compression fractures, and significant height loss in adulthood. Males were in general more severely affected than females. Bone histomorphometry findings in 4 males and 1 female showed severe trabecular osteoporosis, low amount of osteoid, and decreased mineral apposition rate, indicating impaired bone formation; resorption parameters were increased in some. All affected subjects shared a single base substitution (c.73-24T > A) in intron 2 of PLS3 on Xq23. The mutation, confirmed by Sanger sequencing, segregated according to the skeletal phenotype. The mutation introduces a new acceptor splice site with a predicted splice score of 0.99 and, thereby, as confirmed by cDNA sequencing, induces the insertion of 22 bases between exons 2 and 3, causing a frameshift and premature termination of mRNA translation (p.Asp25Alafs*17). The mutation affects the first N-terminal calcium-binding EF-hand domain and abolishes all calcium- and actin-binding domains of the protein. Our results confirm the role of PLS3 mutations in early onset osteoporosis. The mechanism whereby PLS3 affects bone health is unclear, but it may be linked to osteocyte dendrite function and skeletal mechanosensing. Future studies are needed to elucidate the role of PLS3 in osteoporosis and to define optimal treatment. © 2014 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]
Published: 2015
Full Text: View/download PDF

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

Author: 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 I, Kals, Mart, Mägi, Reedik, Pärn, Kalle, Hämäläinen, Eija, Huang, Hailiang, Byrnes, Andrea E, Franke, Lude, Huang, Jie, Stergiakouli, Evie, Lee, Phil H, Sandor, Cynthia, Webber, Caleb, Cader, Zameel, Muller-Myhsok, Bertram, Schreiber, Stefan, Meitinger, Thomas, Eriksson, Johan G, Salomaa, Veikko, Heikkilä, Kauko, Loehrer, Elizabeth, Uitterlinden, Andre G, Hofman, Albert, van Duijn, Cornelia M, Cherkas, Lynn, Pedersen, Linda M, Stubhaug, Audun, Nielsen, Christopher S, Männikkö, Minna, Mihailov, Evelin, Milani, Lili, Göbel, Hartmut, Esserlind, Ann-Louise, Christensen, Anne Francke, 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, van den Maagdenberg, Arn M J M, 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, and Palotie, Aarno
Published: 2016
Full Text: View/download PDF

45. Migraine with aura – genetic susceptibility variants

Author: Nuottamo, Marjo, University of Helsinki, Faculty of Medicine, Doctoral Programme in Biomedicine, Folkhälsan Research Center, Helsinki, Finland, Institute for Molecular Medicine Finland (FIMM),Helsinki Institute of Life Science (HiLIFE),University of Helsinki, Helsinki, Finland, Helsingin yliopisto, lääketieteellinen tiedekunta, Biolääketieteellinen tohtoriohjelma, Helsingfors universitet, medicinska fakulteten, Doktorandprogrammet i biomedicin, Hiltunen, Mikko, Wessman, Maija, and Kaunisto, Mari
Subjects: medical Genetics
Abstract: Migraine is a complex headache disorder affecting approximately 15% of the adult population worldwide. It has a great impact on both individual patients and society. According to the Global Burden of Disease Study, migraine is one of the most costly and disabling neurological diseases. There are two main subtypes of migraine: migraine without aura and migraine with aura. Migraine without aura is the most common subtype of migraine. However, one-third of migraine patients experience neurological aura symptoms. In most cases, aura is visual, including scintillating scotoma and loss of vision type symptoms, but it can also be sensory, motor or result in speech disturbance. In hemiplegic migraine, a rare form of migraine with aura, the aura is characterized by motor weakness. The exact pathophysiological mechanisms underlying migraine are still unknown. Both family and twin studies have shown that migraine is hereditary. Recent genome-wide association studies (GWAS) have revealed the polygenic nature of common forms of migraine, while high-impact mutations have been found mainly in familial hemiplegic migraine (FHM). FHM is suggested to be a monogenic disorder with three major causative genes: CACNA1A, ATP1A2 and SCN1A. Genetic variants in these ion-transport/channel genes have also been associated with rare monogenic forms of epilepsy. The aim of this doctoral thesis was to identify genetic susceptibility factors for migraine with aura and migraine-epilepsy phenotype. We applied targeted and genome-wide approaches in a large and well-characterized Finnish migraine family sample (1,967 families with 8,937 family members). The first part of the thesis defined hemiplegic migraine as a clinically and genetically heterogeneous disease. In terms of headache characteristics and neurological aura symptoms, hemiplegic migraine patients appeared at the extreme end of the migraine with aura symptom spectrum. Our study also showed that mutations in CACNA1A, ATP1A2 and SCN1A are not the major cause of hemiplegic migraine in Finnish patients, as only 9% (4/45) of the studied FHM families and none of the sporadic cases (n=201) carried pathogenic exonic variants in these genes. These data suggest that there are additional genetic factors contributing to the hemiplegic migraine phenotype. In the second part of this thesis, we utilized data obtained from a previously published migraine GWAS to calculate polygenic risk scores (PRS) for 8,319 participants from the Finnish migraine family collection and 14,470 FINRISK population-based samples. Results showed that common polygenic variation significantly contributes to the familial aggregation of migraine. The polygenic burden was higher in familial migraine cases than in population cases. Furthermore, the polygenic burden was increased across all of the studied migraine with aura and migraine without aura subtypes in the family dataset compared with the population controls. Patients with typical migraine aura or hemiplegic migraine carried a higher load compared with patients having migraine without aura. Our findings are especially interesting considering that FHM has been suggested to be a monogenic disorder primarily driven by rare, high-impact variants. The third part of this thesis focused on a previously identified migraine-epilepsy susceptibility locus on chromosome 12q24.2-q24.3 identified in a large multi-generational Finnish migraine-epilepsy family including 120 individuals. We defined a 450 kbp haplotype that was shared among 12 out of 13 epilepsy patients. This segment covers almost the entire NCOR2 gene, which plays an important regulatory role during brain development. Interestingly, one of the 123 migraine risk loci recently reported by the International Headache Genetics Consortium also co-localized with this region. Our results suggest that NCOR2 could potentially have a role in both migraine and epilepsy and could thus contribute to the susceptibility of both of these paroxysmal brain diseases. However, further studies are needed to identify the actual causal variants. Overall, the results of this doctoral thesis highlight migraine as a clinically and genetically heterogeneous disease. Our results suggest that migraine with typical aura and hemiplegic migraine share a similar genetic background with a high polygenic load. Even FHM may not be a true monogenic disease, but rather a disease in which common risk variants, together with rare pathogenic variants and environmental risk factors, contribute to the disease outcome. Furthermore, our results provide genetic evidence from a large multi-generational Finnish family for potentially shared pathophysiology underlying both epilepsy and migraine. Migreeni on yleinen kohtauksellinen päänsärkysairaus. Kolmasosalla migreenipotilaista kohtauksiin liittyy auraoire, joka voi olla näkö-, puhe- tai tuntohäiriö. Harvinaisessa hemiplegisessä migreenissä aura esiintyy toisella puolella kehoa puutumista ja voimattomuutta aiheuttavana oireena. Migreenin patofysiologiaa ei vielä täysin tunneta. Laajat geenitutkimukset ovat tunnistaneet yli sata migreeniriskiä hieman lisäävää perimän vaihtelevaa kohtaa (geenivarianttia). Sairastumisriskiin merkittävästi yksinään vaikuttavia variantteja on tunnistettu vain monogeenisenä sairautena pidetylle hemiplegiselle migreenille. Tässä väitöskirjatutkimuksessa selvitettiin aurallisen migreenin sekä migreenin ja epilepsian yhteisesiintymisen geneettistä taustaa hyödyntämällä suurta suomalaista migreeniperheaineistoa (1967 perhettä, 8937 henkilöä). Tutkimuksen ensimmäisen osatyön tulokset osoittivat, että hemipleginen migreeni on osa aurallisen migreenin oirejatkumoa, vaikkakin hemiplegistä migreeniä sairastavien oireet ovat keskimäärin vakavampia kuin tyypillistä aurallista migreeniä sairastavilla. Tulokset osoittivat myös, että kolme tunnettua hemiplegisen migreenin alttiusgeeniä (CACNA1A, ATP1A2 ja SCN1A) eivät yksinään riitä selittämään hemiplegisen migreenin esiintymistä suomalaisissa perheissä. Ainoastaan 9 %:lta tutkituista perheistä (4/45) löydettiin todennäköinen sairausvariantti kyseisistä geeneistä. Tutkimuksen toisen osatyön tulokset osoittivat, että monien geneettisten riskitekijöiden yhteisvaikutus selittää migreenin esiintymistä suvuissa. Tutkimuksessa havaittiin myös eroja eri migreenityyppien välillä. Yleisten geneettisten riskitekijöiden muodostama taakka oli suurempi aurallisessa migreenissä, mukaan lukien hemiplegistä migreeniä sairastavat henkilöt, kuin aurattomassa migreenissä. Aiemmin hemiplegisen migreenin on ajateltu aiheutuvan pelkästään harvinaisista varianteista. Tutkimuksen viimeisessä osatyössä keskityttiin yhteen suureen perheeseen ja siinä tunnistettuun migreenille ja epilepsialle altistavaan 12q24.31 kromosomialueeseen. Jatkotutkimukset osoittivat aivojen kehitykseen vaikuttavan NCOR2-geenin todennäköisimmäksi epilepsian alttiusgeeniksi kyseisessä perheessä. Yksi migreenin riskialueista sijaitsee samalla genomialueella, mikä tukee alueen merkitystä myös migreenin taustalla. Kokonaisuudessaan tämän väitöstutkimuksen tulokset viittaavat siihen, että migreeni on kliinisesti ja geneettisesti heterogeeninen sairaus, jonka kehittymiseen vaikuttavat useat geenivariantit yhdessä ulkoisten tekijöiden kanssa. Aurallisen migreenin kliiniset oireet muodostavat jatkumon, jossa hemiplegisen migreenin oireet ovat kestoltaan, määrältään ja tyypiltään kaikkein vakavimpia. Yllättäen myös geneettisten riskitekijöiden yhteisvaikutus on aurallisilla ja hemiplegisillä migreenipotilailla kaikkein suurin.
Published: 2022

46. Systematic re-evaluation of genes from candidate gene association studies in migraine using a large genome-wide association data set.

Author: de Vries, Boukje, Anttila, Verneri, Freilinger, Tobias, Wessman, Maija, Kaunisto, Mari A., Kallela, Mikko, Artto, Ville, Vijfhuizen, Lisanne S., Göbel, Hartmut, Dichgans, Martin, Kubisch, Christian, Ferrari, Michel D., Palotie, Aarno, Terwindt, Gisela M., van den Maagdenberg, Arn M. J. M., van den Maagdenberg, Arn Mjm, and International Headache Genetics Consortium
Subjects: *MIGRAINE, *SINGLE nucleotide polymorphisms, *PATHOLOGICAL physiology, *HEADACHE, *MIGRAINE aura, *GENETICS, *DISEASE susceptibility, *GENETIC polymorphisms, *GENETIC techniques
Abstract: Background: Before the genome-wide association (GWA) era, many hypothesis-driven candidate gene association studies were performed that tested whether DNA variants in genes that had been selected based on prior knowledge about migraine pathophysiology were associated with migraine. Most studies involved small sample sets without robust replication, thereby making the risk of false-positive findings high. Genome-wide marker data of thousands of migraine patients and controls from the International Headache Genetics Consortium provide a unique opportunity to re-evaluate key findings from candidate gene association studies (and other non-GWA genetic studies) in a much larger data set.Methods: We selected 21 genes from published candidate gene association studies and six additional genes from other non-GWA genetic studies in migraine. Single nucleotide polymorphisms (SNPs) in these genes, as well as in the regions 500 kb up- and downstream, were inspected in IHGC GWAS data from 5175 clinic-based migraine patients with and without aura and 13,972 controls.Results: None of the SNPs in or near the 27 genes, including the SNPs that were previously found to be associated with migraine, reached the Bonferroni-corrected significance threshold; neither when analyzing all migraine patients together, nor when analyzing the migraine with and without aura patients or males and females separately.Conclusion: The available migraine GWAS data provide no clear evidence for involvement of the previously reported most promising candidate genes in migraine. [ABSTRACT FROM AUTHOR]
Published: 2016
Full Text: View/download PDF

47. NCOR2 is a novel candidate gene for migraine-epilepsy phenotype.

Author: Nuottamo ME, Häppölä P, Artto V, Hautakangas H, Pirinen M, Hiekkalinna T, Ellonen P, Lepistö M, Hämäläinen E, Siren A, Lehesjoki AE, Kallela M, Palotie A, Kaunisto MA, and Wessman M
Subjects: Genetic Predisposition to Disease genetics, Genome-Wide Association Study, Humans, Nuclear Receptor Co-Repressor 2 genetics, Phenotype, Polymorphism, Single Nucleotide genetics, Epilepsy genetics, Migraine Disorders genetics
Abstract: Hypothesis: To identify genetic factors predisposing to migraine-epilepsy phenotype utilizing a multi-generational family with known linkage to chr12q24.2-q24.3., Methods: We used single nucleotide polymorphism (SNP) genotyping and next-generation sequencing technologies to perform linkage, haplotype, and variant analyses in an extended Finnish migraine-epilepsy family (n = 120). In addition, we used a large genome-wide association study (GWAS) dataset of migraine and two biobank studies, UK Biobank and FinnGen, to test whether variants within the susceptibility region associate with migraine or epilepsy related phenotypes in a population setting., Results: The family showed the highest evidence of linkage (LOD 3.42) between rs7966411 and epilepsy. The haplotype shared among 12 out of 13 epilepsy patients in the family covers almost the entire NCOR2 and co-localizes with one of the risk loci of the recent GWAS on migraine. The haplotype harbors nine low-frequency variants with potential regulatory functions. Three of them, in addition to two common variants, show nominal associations with neurological disorders in either UK Biobank or FinnGen., Conclusion: We provide several independent lines of evidence supporting association between migraine-epilepsy phenotype and NCOR2 . Our study suggests that NCOR2 may have a role in both migraine and epilepsy and thus would provide evidence for shared pathophysiology underlying these two diseases.
Published: 2022
Full Text: View/download PDF

48. Polygenic risk provides biological validity for the ICHD-3 criteria among Finnish migraine families.

Author: Häppölä P, Gormley P, Nuottamo ME, Artto V, Sumelahti ML, Nissilä M, Keski-Säntti P, Ilmavirta M, Kaunisto MA, Hämäläinen EI, Ripatti S, Pirinen M, Wessman M, Palotie A, and Kallela M
Subjects: Finland epidemiology, Headache, Humans, Headache Disorders, Migraine Disorders diagnosis, Migraine Disorders genetics, Migraine with Aura diagnosis
Abstract: Background: Migraine is diagnosed using the extensively field-tested International Classification of Headache Disorders (ICHD-3) consensus criteria derived by the International Headache Society. To evaluate the criteria in respect to a measurable biomarker, we studied the relationship between the main ICHD-3 criteria and the polygenic risk score, a measure of common variant burden in migraine., Methods: We used linear mixed models to study the correlation of ICHD-3 diagnostic criteria, underlying symptoms, and main diagnoses with the polygenic risk score of migraine in a cohort of 8602 individuals from the Finnish Migraine Genome Project., Results: Main diagnostic categories and all underlying diagnostic criteria formed a consistent continuum along the increasing polygenic burden. Polygenic risk was associated with the heterogeneous clinical picture starting from the non-migraine headache (mean 0.07; 95% CI 0.02-0.12; p = 0.008 compared to the non-headache group), to probable migraine (mean 0.13; 95% CI 0.08-0.18; p < 0.001), migraine headache (mean 0.17; 95% CI 0.14-0.21; p < 0.001) and migraine with typical visual aura (mean 0.29; 95% CI 0.26-0.33; p < 0.001), all the way to the hemiplegic aura (mean 0.37; 95% CI 0.31-0.43; p < 0.001). All individual ICHD-3 symptoms and the total number of reported symptoms, a surrogate of migraine complexity, demonstrated a clear inclination with an increasing polygenic risk., Conclusions: The complex migraine phenotype progressively follows the polygenic burden from individuals with no headache to non-migrainous headache and up to patients with attacks manifesting all the features of the ICHD-3 headache and aura. Results provide further biological support for the ICHD-3 diagnostic criteria.
Published: 2022
Full Text: View/download PDF

49. Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine.

Author: Gormley P, Anttila V, Winsvold BS, Palta P, Esko T, Pers TH, Farh KH, Cuenca-Leon E, Muona M, Furlotte NA, Kurth T, Ingason A, McMahon G, Ligthart L, Terwindt GM, Kallela M, Freilinger TM, Ran C, Gordon SG, Stam AH, Steinberg S, Borck G, Koiranen M, Quaye L, Adams HH, Lehtimäki T, Sarin AP, Wedenoja J, Hinds DA, Buring JE, Schürks M, Ridker PM, Hrafnsdottir MG, Stefansson H, Ring SM, Hottenga JJ, Penninx BW, Färkkilä M, Artto V, Kaunisto M, Vepsäläinen S, Malik R, Heath AC, Madden PA, Martin NG, Montgomery GW, Kurki MI, Kals M, Mägi R, Pärn K, Hämäläinen E, Huang H, Byrnes AE, Franke L, Huang J, Stergiakouli E, Lee PH, Sandor C, Webber C, Cader Z, Muller-Myhsok B, Schreiber S, Meitinger T, Eriksson JG, Salomaa V, Heikkilä K, Loehrer E, Uitterlinden AG, Hofman A, van Duijn CM, Cherkas L, Pedersen LM, Stubhaug A, Nielsen CS, Männikkö M, Mihailov E, Milani L, Göbel H, Esserlind AL, Christensen AF, Hansen TF, Werge T, Kaprio J, Aromaa AJ, Raitakari O, Ikram MA, Spector T, Järvelin MR, Metspalu A, Kubisch C, Strachan DP, Ferrari MD, Belin AC, Dichgans M, Wessman M, van den Maagdenberg AM, Zwart JA, Boomsma DI, Smith GD, Stefansson K, Eriksson N, Daly MJ, Neale BM, Olesen J, Chasman DI, Nyholt DR, and Palotie A
Subjects: Case-Control Studies, Genome-Wide Association Study, Genomics, Humans, Muscle, Smooth metabolism, Vascular Diseases genetics, Genetic Loci genetics, Genetic Markers genetics, Genetic Predisposition to Disease, Migraine Disorders genetics, Polymorphism, Single Nucleotide genetics
Abstract: Migraine is a debilitating neurological disorder affecting around one in seven people worldwide, but its molecular mechanisms remain poorly understood. There is some debate about whether migraine is a disease of vascular dysfunction or a result of neuronal dysfunction with secondary vascular changes. Genome-wide association (GWA) studies have thus far identified 13 independent loci associated with migraine. To identify new susceptibility loci, we carried out a genetic study of migraine on 59,674 affected subjects and 316,078 controls from 22 GWA studies. We identified 44 independent single-nucleotide polymorphisms (SNPs) significantly associated with migraine risk (P < 5 × 10(-8)) that mapped to 38 distinct genomic loci, including 28 loci not previously reported and a locus that to our knowledge is the first to be identified on chromosome X. In subsequent computational analyses, the identified loci showed enrichment for genes expressed in vascular and smooth muscle tissues, consistent with a predominant theory of migraine that highlights vascular etiologies.
Published: 2016
Full Text: View/download PDF

50. Gene-based pleiotropy across migraine with aura and migraine without aura patient groups.

Author: Zhao H, Eising E, de Vries B, Vijfhuizen LS, Anttila V, Winsvold BS, Kurth T, Stefansson H, Kallela M, Malik R, Stam AH, Ikram MA, Ligthart L, Freilinger T, Alexander M, Müller-Myhsok B, Schreiber S, Meitinger T, Aromas A, Eriksson JG, Boomsma DI, van Duijn CM, Zwart JA, Quaye L, Kubisch C, Dichgans M, Wessman M, Stefansson K, Chasman DI, Palotie A, Martin NG, Montgomery GW, Ferrari MD, Terwindt GM, van den Maagdenberg AM, and Nyholt DR
Subjects: Adult, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Genetic Pleiotropy genetics, Migraine with Aura genetics, Migraine without Aura genetics, Receptors, Neuropeptide genetics
Abstract: Introduction: It is unclear whether patients diagnosed according to International Classification of Headache Disorders criteria for migraine with aura (MA) and migraine without aura (MO) experience distinct disorders or whether their migraine subtypes are genetically related., Aim: Using a novel gene-based (statistical) approach, we aimed to identify individual genes and pathways associated both with MA and MO., Methods: Gene-based tests were performed using genome-wide association summary statistic results from the most recent International Headache Genetics Consortium study comparing 4505 MA cases with 34,813 controls and 4038 MO cases with 40,294 controls. After accounting for non-independence of gene-based test results, we examined the significance of the proportion of shared genes associated with MA and MO., Results: We found a significant overlap in genes associated with MA and MO. Of the total 1514 genes with a nominally significant gene-based p value (pgene-based ≤ 0.05) in the MA subgroup, 107 also produced pgene-based ≤ 0.05 in the MO subgroup. The proportion of overlapping genes is almost double the empirically derived null expectation, producing significant evidence of gene-based overlap (pleiotropy) (pbinomial-test = 1.5 × 10(-4)). Combining results across MA and MO, six genes produced genome-wide significant gene-based p values. Four of these genes (TRPM8, UFL1, FHL5 and LRP1) were located in close proximity to previously reported genome-wide significant SNPs for migraine, while two genes, TARBP2 and NPFF separated by just 259 bp on chromosome 12q13.13, represent a novel risk locus. The genes overlapping in both migraine types were enriched for functions related to inflammation, the cardiovascular system and connective tissue., Conclusions: Our results provide novel insight into the likely genes and biological mechanisms that underlie both MA and MO, and when combined with previous data, highlight the neuropeptide FF-amide peptide encoding gene (NPFF) as a novel candidate risk gene for both types of migraine., (© International Headache Society 2015.)
Published: 2016
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Database

Publisher

100 results on '"Wessman, Maija"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources