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

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Gormley, Padhraig, Kurki, Mitja I, Hiekkala, Marjo Eveliina, Veerapen, Kumar, Häppölä, Paavo, Mitchell, Adele A, Lal, Dennis, Palta, Priit, Surakka, Ida, Kaunisto, Mari Anneli et al (show 124 more authors) , Hämäläinen, 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, Runz, Heiko, Daly, Mark J, Neale, Benjamin M, Ripatti, Samuli, Kallela, Mikko, Wessman, Maija, Palotie, Aarno, 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 AM, Pitts, Steven J, Sathirapongsasuti, J Fah, Sazonova, Olga V, Shelton, Janie F, Shringarpure, Suyash, Tian, Chao, Tung, Joyce Y, Vacic, Vladimir, Wilson, Catherine H, Anttila, Verneri, Artto, Ville, 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, Frants, Rune R, Freilinger, Tobias, Furlotte, Nick, Gormley, Padhraig, Griffiths, Lyn, Hamalainen, Eija, Hansen, Thomas Folkmann, Hiekkala, Marjo, Ikram, M Arfan, Ingason, Andres, Järvelin, 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 ORCID: 0000-0002-0719-101X, Neale, Benjamin M, Northover, Carrie, Nyholt, Dale R, Olesen, Jes, Palotie, Aarno, Palta, Priit, Pedersen, Linda, Pedersen, Nancy, Posthuma, Danielle, Pozo-Rosich, Patricia, Pressman, Alice, Quaye, Lydia, Raitakari, Olli, 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 and Zwart, John-Anker (2018) Common Variant Burden Contributes to the Familial Aggregation of Migraine in 1,589 Families. Neuron, 98 (4). 743-753.e4.

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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.

Item Type:	Article
Additional Information:	publisher: Elsevier articletitle: Common Variant Burden Contributes to the Familial Aggregation of Migraine in 1,589 Families journaltitle: Neuron articlelink: http://dx.doi.org/10.1016/j.neuron.2018.04.014 content_type: article copyright: © 2018 Elsevier Inc.
Uncontrolled Keywords:	23andMe Research Team, International Headache Genetics Consortium (IHGC), Humans, Genetic Predisposition to Disease, Genotype, Multifactorial Inheritance, Phenotype, Adult, Middle Aged, Female, Male, Migraine Disorders, Migraine with Aura, Migraine without Aura, Genetic Variation, Genome-Wide Association Study
Depositing User:	Symplectic Admin
Date Deposited:	10 Jul 2018 07:39
Last Modified:	19 Jan 2023 01:30
DOI:	10.1016/j.neuron.2018.04.014
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3023569

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• Common Variant Burden Contributes to the Familial Aggregation of Migraine in 1,589 Families. (deposited 31 May 2018 09:01)
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