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

J Med Genet. 2018 Dec;55(12):831-836. doi: 10.1136/jmedgenet-2018-105359. Epub 2018 Sep 28.

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.

Keywords: genetics; genome-wide; neurology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • African Americans / genetics*
  • Alleles
  • Child
  • Chromosomes, Human, Pair 5*
  • Computational Biology / methods
  • Female
  • Gene Frequency
  • Genetic Variation*
  • Genome-Wide Association Study
  • Genomics / methods
  • Genotype
  • Humans
  • Linkage Disequilibrium
  • Male
  • Migraine Disorders / diagnosis*
  • Migraine Disorders / epidemiology
  • Migraine Disorders / genetics*
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci*
  • United States / epidemiology