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

BackgroundA 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.MethodsAmong 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.ResultsWe 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, F139Wfs*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 (χ2 = 0.96, 1 df, p = 0.33).ConclusionsSince 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.

RERconverge: an R package for associating evolutionary rates with convergent traits

Motivation When different lineages of organisms independently adapt to similar environments, selection often acts repeatedly upon the same genes, leading to signatures of convergent evolutionary rate shifts at these genes. With the increasing availability of genome sequences for organisms displaying a variety of convergent traits, the ability to identify genes with such convergent rate signatures would enable new insights into the molecular basis of these traits. Results Here we present the R package RERconverge, which tests for association between relative evolutionary rates of genes and the evolution of traits across a phylogeny. RERconverge can perform associations with binary and continuous traits, and it contains tools for visualization and enrichment analyses of association results. Availability and implementation RERconverge source code, documentation and a detailed usage walk-through are freely available at https://github.com/nclark-lab/RERconverge. Datasets for mammals, Drosophila and yeast are available at https://bit.ly/2J2QBnj. Supplementary information Supplementary data are available at Bioinformatics online.

RERconverge: an R package for associating evolutionary rates with convergent traits

Motivation: When different lineages of organisms independently adapt to similar environments, selection often acts repeatedly upon the same genes, leading to signatures of convergent evolutionary rate shifts at these genes. With the increasing availability of genome sequences for organisms displaying a variety of convergent traits, the ability to identify genes with such convergent rate signatures would enable new insights into the molecular basis of these traits.Results: Here we present the R package RERconverge, which tests for association between relative evolutionary rates of genes and the evolution of traits across a phylogeny. RERconverge can perform associations with binary and continuous traits, and it contains tools for visualization and enrichment analyses of association results.Availability: RERconverge source code, documentation, and a detailed usage walk-through are freely available at https://github.com/nclark-lab/RERconverge. Datasets for mammals, Drosophila, and yeast are available at https://bit.ly/2J2QBnj.Contact:[email protected] information: Supplementary information, containing detailed vignettes for usage of RERconverge, are available at Bioinformatics online.