A1 Refereed original research article in a scientific journal
Common Variant Burden Contributes to the Familial Aggregation of Migraine in 1,589 Families
Authors: Padhraig Gormley, Mitja I. Kurki, Marjo Eveliina Hiekkala, Kumar Veerapen, Paavo Häppölä, Adele A. Mitchell, Dennis Lal, Priit Palta, Ida Surakka, Mari Anneli Kaunisto, Eija Hämäläinen, Salli Vepsäläinen, Hannele Havanka, Hanna Harno, Matti Ilmavirta, Markku Nissilä, Erkki Säkö, Marja-Liisa Sumelahti, Jarmo Liukkonen, Matti Sillanpää, Liisa Metsähonkala, Seppo Koskinen, Terho Lehtimäki, Olli Raitakari, Minna Männikko, Caroline Ran, Andrea Carmine Belin, Pekka Jousilahti, Verneri Anttila, Veikko Salomaa, Ville Artto, Markus Färkkilä, 23andMe Research Team, International Headache Genetics Consortium (IHGC), Heiko Runz, Mark J. Daly, Benjamin M. Neale, Samuli Ripatti, Mikko Kallela, Maija Wessman, Aarno Palotie
Publisher: CELL PRESS
Publication year: 2018
Journal: Neuron
Journal name in source: NEURON
Journal acronym: NEURON
Volume: 98
Issue: 4
First page : 743
Last page: 753.e4
Number of pages: 15
ISSN: 0896-6273
eISSN: 1097-4199
DOI: https://doi.org/10.1016/j.neuron.2018.04.014
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 significantly higher common variant burden in familial cases (n = 5,317, OR = 1.76, 95% CI = 1.71-1.81, p = 1.7 x 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 x 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.
