Common polygenic variation contributes to risk of migraine in the Norfolk Island population

A. J. Rodriguez-Acevedo, M. A. Ferreira, Miles C. Benton, Melanie A. Carless, Harald H. Goring, Joanne E. Curran, John Blangero, R. A. Lea, L. R. Griffiths

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Migraine has been defined as a common disabling primary headache disorder. Epidemiology studies have provided with the undeniable evidence of genetic components as active players in the development of the disease under a polygenic model in which multiple risk alleles exert modest individual effects. Our objective was to test the contribution of a polygenic effect to migraine risk in the Norfolk Island population using a panel of SNPs reported to be disease associated in published migraine GWAS. We also investigated whether individual SNPs were associated with gene expression levels measured in whole blood. Polygenic scores were calculated in a total of 285 related individuals (74 cases, 211 controls) from the Norfolk Island using 51 SNPs previously reported to be associated with migraine in published GWAS. The association between polygenic score and migraine case–control status was tested using logistic regression. Results indicate that a migraine polygenic risk score was associated with migraine case–control status in this population (P = 0.016). This supports the hypothesis that multiple SNPs with weak effects collectively contribute to migraine risk in this population. Amongst the SNPs included in the polygenic model, four were associated with the expression of the USMG5 gene, including rs171251 (P = 0.012). Results from this study provide evidence for a polygenic contribution to migraine risk in an isolated population and highlight specific SNPs that regulate the expression of USMG5, a gene critical for mitochondrial function.

Original languageEnglish (US)
Pages (from-to)1079-1087
Number of pages9
JournalHuman Genetics
Volume134
Issue number10
DOIs
StatePublished - Jul 29 2015
Externally publishedYes

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Melanesia
Migraine Disorders
Single Nucleotide Polymorphism
Population
Genome-Wide Association Study
Primary Headache Disorders
Gene Expression
Mitochondrial Genes
Epidemiology
Logistic Models
Alleles

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Rodriguez-Acevedo, A. J., Ferreira, M. A., Benton, M. C., Carless, M. A., Goring, H. H., Curran, J. E., ... Griffiths, L. R. (2015). Common polygenic variation contributes to risk of migraine in the Norfolk Island population. Human Genetics, 134(10), 1079-1087. https://doi.org/10.1007/s00439-015-1587-9

Common polygenic variation contributes to risk of migraine in the Norfolk Island population. / Rodriguez-Acevedo, A. J.; Ferreira, M. A.; Benton, Miles C.; Carless, Melanie A.; Goring, Harald H.; Curran, Joanne E.; Blangero, John; Lea, R. A.; Griffiths, L. R.

In: Human Genetics, Vol. 134, No. 10, 29.07.2015, p. 1079-1087.

Research output: Contribution to journalArticle

Rodriguez-Acevedo, AJ, Ferreira, MA, Benton, MC, Carless, MA, Goring, HH, Curran, JE, Blangero, J, Lea, RA & Griffiths, LR 2015, 'Common polygenic variation contributes to risk of migraine in the Norfolk Island population', Human Genetics, vol. 134, no. 10, pp. 1079-1087. https://doi.org/10.1007/s00439-015-1587-9
Rodriguez-Acevedo AJ, Ferreira MA, Benton MC, Carless MA, Goring HH, Curran JE et al. Common polygenic variation contributes to risk of migraine in the Norfolk Island population. Human Genetics. 2015 Jul 29;134(10):1079-1087. https://doi.org/10.1007/s00439-015-1587-9
Rodriguez-Acevedo, A. J. ; Ferreira, M. A. ; Benton, Miles C. ; Carless, Melanie A. ; Goring, Harald H. ; Curran, Joanne E. ; Blangero, John ; Lea, R. A. ; Griffiths, L. R. / Common polygenic variation contributes to risk of migraine in the Norfolk Island population. In: Human Genetics. 2015 ; Vol. 134, No. 10. pp. 1079-1087.
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