Migraines run in families because of an accumulation of independent genetic risk variants, the largest genetic family study on migraine has revealed.
The Finnish study also showed that the genetic burden was greater in patients that experience aura symptoms during attacks or have an early age of onset of migraine.
Published in Neuron, the study was based on medical history and genetic data of 1,589 Finnish migraine families comprising more than 8,300 individuals.
Researchers from the University of Helsinki, Helsinki University Central Hospital and the Broad Institute of MIT and Harvard co-ordinated the study, which built on previous research that identified more than 40 significant genetic risk variants that predispose individuals to migraine.
In the present study, the team combined information from all these implicated risk variants and calculated a personal genetic risk score for each of the study participants.
This genetic risk score was used to estimate and compare the genetic burden conferred by common variants in different migraine patient subgroups.
First author Dr Padhraig Gormley from the Broad Institute of MIT and Harvard, said: “Both rare, high-impact and common genetic variants with smaller impact could contribute to the familial aggregation of migraine. In this study, we wanted to find out which one is more important and whether the genetic load is higher in certain types of migraine.”
One third of migraine patients experience aura during attacks. The Finnish family migraine cohort comprised 2,420 patients with a diagnosis of migraine with typical aura and 540 patients with less common hemiplegic aura symptoms.
The family cohort was also compared against another large Finnish sample, the FINRISK population cohort with almost 15,000 participants, including 1,100 with migraine.
The researchers observed an overall increased genetic risk score in familial migraine cases compared to general migraine cases from the population and clear differences of the common variant load across different migraine subtypes.
Professor Aarno Palotie from the Institute for Molecular Medicine Finland FIMM at the University of Helsinki, said: “Our study supports the hypothesis that migraine subtypes are genetically heterogeneous diseases, and that common polygenic variation significantly contributes to the aggregation of the disease in families, both for common and rare migraine subtypes.
“We were surprised by the impact of the common variants in these families. However, much of the genetic predisposition to migraine still remains unexplained. It is likely that further studies will reveal more common and rare migraine risk variants.”
Gormley et al. Common variant burden contributes to the familial aggregation of migraine in 1,589 families. Neuron May 2018, in press; doi: 10.1016/j.neuron.2018.04.014
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