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

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  • 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 Männikkö
  • Caroline Ran
  • Andrea Carmine Belin
  • Pekka Jousilahti
  • Verneri Anttila
  • Veikko Salomaa
  • Ville Artto
  • Markus Färkkilä
  • Michelle Agee
  • Babak Alipanahi
  • Adam Auton
  • Robert K. Bell
  • Katarzyna Bryc
  • Sarah L. Elson
  • Pierre Fontanillas
  • Nicholas A. Furlotte
  • Karen E. Huber
  • Aaron Kleinman
  • Nadia K. Litterman
  • Jennifer C. McCreight
  • Matthew H. McIntyre
  • Anne Francke Christensen
  • Ann Louise Esserlind
  • Thomas Folkmann Hansen
  • Andres Ingason
  • Jes Olesen
  • 23andMe Research Team
  • International Headache Genetics Consortium (IHGC)
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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.

Original languageEnglish
JournalNeuron
Volume98
Issue number4
Pages (from-to)743-753.e4
ISSN0896-6273
DOIs
Publication statusPublished - 16 May 2018

    Research areas

  • disease aggregation, familial aggregation, families, genome-wide association study, GWAS, hemiplegic migraine, migraine, migraine with aura, polygenic risk score, PRS

ID: 55288910