title: Common polygenic variation contributes to risk of migraine in the Norfolk Island population.
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.
authors.affiliation: Genomics Research Centre, Institute of Health and Biomedical Innovation, QUT, Brisbane, Australia.
authors.forename: A J
authors.initials: AJ
authors.lastname: Rodriguez-Acevedo
authors.affiliation: QIMR-Berghofer Medical Research Institute, Brisbane, Australia.
authors.forename: M A
authors.initials: MA
authors.lastname: Ferreira
authors.affiliation: Genomics Research Centre, Institute of Health and Biomedical Innovation, QUT, Brisbane, Australia.
authors.forename: Miles C
authors.initials: MC
authors.lastname: Benton
authors.affiliation: Texas Biomedical Research Institute, San Antonio, TX, 78227-5301, USA.
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Carless
authors.affiliation: South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, 78520, USA.
authors.forename: Harald H
authors.initials: HH
authors.lastname: Goring
authors.affiliation: South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, 78520, USA.
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Curran
authors.affiliation: South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, 78520, USA.
authors.forename: John
authors.initials: J
authors.lastname: Blangero
authors.affiliation: Genomics Research Centre, Institute of Health and Biomedical Innovation, QUT, Brisbane, Australia.
authors.forename: R A
authors.initials: RA
authors.lastname: Lea
authors.affiliation: Genomics Research Centre, Institute of Health and Biomedical Innovation, QUT, Brisbane, Australia. lyn.griffiths@qut.edu.au.
authors.forename: L R
authors.identifier: http://orcid.org/0000-0002-6774-5475
authors.initials: LR
authors.lastname: Griffiths
mesh_terms: D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008542:Melanesia; D008881:Migraine Disorders / Q000235:genetics*; D020412:Multifactorial Inheritance; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci