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Neuron DOI:10.1016/j.neuron.2018.04.014

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

Publication TypeJournal Article
Year of Publication2018
AuthorsGormley, P, Kurki, MI, Hiekkala, MEveliina, Veerapen, K, Häppölä, P, Mitchell, AA, Lal, D, Palta, P, Surakka, I, Kaunisto, MAnneli, Hämäläinen, E, Vepsäläinen, S, Havanka, H, Harno, H, Ilmavirta, M, Nissilä, M, Säkö, E, Sumelahti, M-L, Liukkonen, J, Sillanpää, M, Metsähonkala, L, Koskinen, S, Lehtimäki, T, Raitakari, O, Männikkö, M, Ran, C, Belin, ACarmine, Jousilahti, P, Anttila, V, Salomaa, V, Artto, V, Färkkilä, M, Runz, H, Daly, MJ, Neale, BM, Ripatti, S, Kallela, M, Wessman, M, Palotie, A
Corporate Authors23andMe Research Team, International Headache Genetics Consortium (IHGC)
JournalNeuron
Volume98
Issue4
Pages743-753.e4
Date Published2018 May 16
ISSN1097-4199
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) compared to population cases from the FINRISK cohort (n = 1,101, OR = 1.32, 95% CI = 1.25-1.38, p = 7.2 × 10). 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.

DOI10.1016/j.neuron.2018.04.014
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/29731251?dopt=Abstract

Alternate JournalNeuron
PubMed ID29731251
PubMed Central IDPMC5967411
Grant List / / Wellcome Trust / United Kingdom
U01 MH105666 / MH / NIMH NIH HHS / United States