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

D.I. Boomsma, L. Ligthart, Danielle Posthuma, 23Andme Research Team

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

Funding

FundersFunder number
Academy of Finland Center of Excellence for Complex Disease GeneticsLSM-CT-2004-504837, 312074, FP7-EUROHEADPAIN, 602633
ENGAGE ConsortiumHEALTH-F4-2007-201413
EU/SYNSYS-Synaptic Systems242167
Medicinska Understödsföreningen Liv & Hälsa, Finland
Merck and Co.
NIASC62721
Nordic Information for Action eScience Center
National Institutes of Health
National Institute of Mental HealthU01MH105666
Merck
Helsingin ja Uudenmaan Sairaanhoitopiiri
Yrjö Jahnssonin Säätiö
Wellcome TrustWT089062, 098051
Folkhälsanin Tutkimussäätiö
Swedish Foundation for MS Research2017-01096
Academy of Finland293404, 286500, 139795
Suomen Kulttuurirahasto
Hjärnfonden
Juho Vainion Säätiö
Karolinska Institutet126925, 121584, 129378, 117787, 134309, 286284, 41071, 124282
Signe ja Ane Gyllenbergin Säätiö
Emil Aaltosen Säätiö
Sydäntutkimussäätiö
Sigrid Juséliuksen Säätiö
Tampereen Tuberkuloosisäätiö
Horizon 2020755320
Diabetesliitto
Paavo Nurmen Säätiö
Turun Yliopistollinen KeskussairaalaX51001

    Keywords

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

    Cohort Studies

    • Netherlands Twin Register (NTR)

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