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.
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Contributors HH and XC designed the study and edited the manuscript. XC performed the statistical analysis and drafted the manuscript. RP and JG conducted the TaqMan genotyping assays. MM and JS contributed to DNA sample collection. FM assisted with organising the phenotype data. CH performed the SNP genotyping and QC. YL, JL and PMAS assisted in discussing and revising the manuscript. All authors read and approved the final manuscript.
Funding The study was supported by Institutional Development Funds from the Children’s Hospital of Philadelphia to the Center for Applied Genomics, The Children’s Hospital of Philadelphia Endowed Chair in Genomic Research to HH and by U01HG006830 from the NHGRI (eMERGE).
Competing interests None declared.
Patient consent Parantal/guardian consent obtained.
Ethics approval The Research Ethics Board of CHOP approved this project and provided written informed consent from all subjects by nursing and medical assistant staff under the direction of CHOP clinicians.
Provenance and peer review Not commissioned; externally peer reviewed.
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