MedicalResearch.com Interview with:
Hakon Hakonarson, MD, PhD
Xiao Chang, PhD
The Center for Applied Genomics
Children’s Hospital Philadelphia
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Migraine is a genetic disorder characterized by recurrent and intense headaches often accompanied by visual disturbances. Genome-wide association studies (GWASs) are a powerful hypothesis-free tool for investigating the genetic architecture of human disease. Currently, multiple GWASs have been conducted on European adults with migraine that have successfully identified several migraine susceptibility genes involved in neuronal and vascular functions.
Considering the prevalence of migraines varies across ethnicities, the genetic risk factors may be different in patients of African ancestries and European ancestries. In addition, if migraine presents at an early age (childhood), it may reflect elevated biological predisposition from genetic factors or increased susceptibility to environmental risk factors.
We performed the first GWAS to investigate the susceptibility genes associated with migraine in African-American children. The main out come was that common variants at the 5q33.1 locus in the human genome are associated with migraine risk in African-American children. The genetic underpinnings at this locus responsible for this finding are less relevant in patients of European ancestry.
MedicalResearch.com: What should readers take away from your report?
Response: Genetic variants at the 5q33.1 locus associate with migraine in patients of African American ancestry. Among the genes located at 5q33.1, the expression level of NMUR2 was significantly correlated with the genotypes of identified variants by GWAS. NMUR2 encodes a G protein-coupled receptor of neuromedin-U (NMU), which participates in diverse physiological processes of the central nervous system, and presents the most likely candidate gene involved in the pathogenesis of migraine.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: Future research may focus on identifying new genetic loci in migraine by collecting more African American pediatric samples. We recommend that researchers study the functional role of NMUR2 in neuronal cells or tissue samples from migraine patients as well as by animal models. We hope clinical trials may be conducted to evaluate the efficacy of Small-Molecule Antagonist at Neuromedin U Receptor (NMUR2) in migraine patients of African-American ancestry.
MedicalResearch.com: Is there anything else you would like to add?
Response: We like to thank all the patients and participants that contributed to this study. We have no disclosures related to this work.
Common variants at 5q33.1 predispose to migraine in African-American children
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