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Study of association of migraine susceptibility genes with common migraine in 200,000 exome-sequenced UK Biobank participants

By Katherine Alexis Markel, David Curtis

Posted 02 Dec 2021
medRxiv DOI: 10.1101/2021.12.02.21267184

Background A number of genes have been implicated in rare familial syndromes which have migraine as part of their phenotype but these genes have not previously been implicated in the common form of migraine. Methods Among exome-sequenced participants in the UK Biobank we identified 7,194 migraine cases with the remaining 193,433 participants classified as controls. We investigated ten genes previously reported to be implicated in conditions with migraine as a prominent part of the phenotype and carried out gene and variant based tests for association. Results We found no evidence for association of these genes or variants with the common form of migraine seen in our subjects. In particular, a frameshift variant in KCNK18, F138Wfs*24, which had been shown to segregate with migraine with aura in a multiply affected pedigree was found in 196 (0.10%) controls as well as in 10 (0.14%) cases ({chi}2 = 0.96, 1 df, p = 0.33). Conclusions Since there is no other reported evidence to implicate KCNK18, we conclude that this gene and its product, TRESK, should no longer be regarded as being involved in migraine aetiology. Overall, we do not find that rare, functional variants in genes previously implicated to be involved in familial syndromes including migraine as part of the phenotype make a contribution to the commoner forms of migraine observed in this population.

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