title: Multilocus analysis reveals three candidate genes for Chinese migraine susceptibility.
abstract: Several genome-wide association studies (GWASs) in Caucasian populations have identified 12 loci that are significantly associated with migraine. More evidence suggests that serotonin receptors are also involved in migraine pathophysiology. In the present study, a case-control study was conducted in a cohort of 581 migraine cases and 533 ethnically matched controls among a Chinese population. Eighteen polymorphisms from serotonin receptors and GWASs were selected, and genotyping was performed using a Sequenom MALDI-TOF mass spectrometry iPLEX platform. The genotypic and allelic distributions of MEF2D rs2274316 and ASTN2 rs6478241 were significantly different between migraine patients and controls. Univariate and multivariate analysis revealed significant associations of polymorphisms in the MEF2D and ASTN2 genes with migraine susceptibility. MEF2D, PRDM16 and ASTN2 were also found to be associated with migraine without aura (MO) and migraine with family history. And, MEF2D and ASTN2 also served as genetic risk factors for the migraine without family history. The generalized multifactor dimensionality reduction analysis identified that MEF2D and HTR2E constituted the two-factor interaction model. Our study suggests that the MEF2D, PRDM16 and ASTN2 genes from GWAS are associated with migraine susceptibility, especially MO, among Chinese patients. It appears that there is no association with serotonin receptor related genes.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Xiamen University, Xiamen, China.
authors.forename: X-K
authors.identifier: http://orcid.org/0000-0003-1842-6387
authors.initials: XK
authors.lastname: An
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Xiamen University, Xiamen, China.
authors.forename: J
authors.initials: J
authors.lastname: Fang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Xiamen University, Xiamen, China.
authors.forename: Z-Z
authors.initials: ZZ
authors.lastname: Yu
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Xiamen University, Xiamen, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Lin
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Xiamen University, Xiamen, China.
authors.forename: C-X
authors.initials: CX
authors.lastname: Lu
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Xiamen University, Xiamen, China.|First Clinical Medical College, The First Clinical Medical College of Fujian Medical University, Fuzhou, China.
authors.forename: H-L
authors.initials: HL
authors.lastname: Qu
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Xiamen University, Xiamen, China.|First Clinical Medical College, The First Clinical Medical College of Fujian Medical University, Fuzhou, China.
authors.forename: Q-L
authors.initials: QL
authors.lastname: Ma
mesh_terms: D000328:Adult; D000483:Alleles; D002681:China; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D064326:MEF2 Transcription Factors / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014157:Transcription Factors / Q000187:drug effects / Q000235:genetics*
chemical_list: C000593289:ASTN2 protein, human; D004268:DNA-Binding Proteins; D006023:Glycoproteins; D064326:MEF2 Transcription Factors; C578043:MEF2D protein, human; D009419:Nerve Tissue Proteins; C416371:PRDM16 protein, human; D014157:Transcription Factors
keywords: genetic susceptibility; genome-wide association studies; migraine; polymorphism; serotonin receptor