Common variants at 5q33.1 predispose to migraine in African-American children.

ABSTRACT: BACKGROUND:Genome-wide association studies (GWASs) have identified multiple susceptibility loci for migraine in European adults. However, no large-scale genetic studies have been performed in children or African Americans with migraine. METHODS:We conducted a GWAS of 380 African-American children and 2129 ancestry-matched controls to identify variants associated with migraine. We then attempted to replicate our primary analysis in an independent cohort of 233 African-American patients and 4038 non-migraine control subjects. RESULTS:The results of this study indicate that common variants at 5q33.1 associated with migraine risk in African-American children (rs72793414, p=1.94×10-9). The association was validated in an independent study (p=3.87×10-3) for an overall meta-analysis p value of 3.81×10-10. eQTL (Expression quantitative trait loci) analysis of the Genotype-Tissue Expression data also shows the genotypes of rs72793414 were strongly correlated with the mRNA expression levels of NMUR2 at 5q33.1. NMUR2 encodes a G protein-coupled receptor of neuromedin-U (NMU). NMU, a highly conserved neuropeptide, participates in diverse physiological processes of the central nervous system. CONCLUSIONS:This study provides new insights into the genetic basis of childhood migraine and allow for precision therapeutic development strategies targeting migraine patients of African-American ancestry.

SUBMITTER: Chang X 

PROVIDER: S-EPMC6511513 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature