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A high-density association screen of 155 ion transport genes for involvement with common migraine
- Publication Year :
- 2008
- Publisher :
- Oxford University Press, 2008.
-
Abstract
- The clinical overlap between monogenic Familial Hemiplegic Migraine (FHM) and common migraine subtypes, and the fact that all three FHM genes are involved in the transport of ions, suggest that ion transport genes may underlie susceptibility to common forms of migraine. To test this leading hypothesis, we examined common variation in 155 ion transport genes using 5257 single nucleotide polymorphisms (SNPs) in a Finnish sample of 841 unrelated migraine with aura cases and 884 unrelated non-migraine controls. The top signals were then tested for replication in four independent migraine case-control samples from the Netherlands, Germany and Australia, totalling 2835 unrelated migraine cases and 2740 unrelated controls. SNPs within 12 genes (KCNB2, KCNQ3, CLIC5, ATP2C2, CACNA1E, CACNB2, KCNE2, KCNK12, KCNK2, KCNS3, SCN5A and SCN9A) with promising nominal association (0.00041 < P < 0.005) in the Finnish sample were selected for replication. Although no variant remained significant after adjusting for multiple testing nor produced consistent evidence for association across all cohorts, a significant epistatic interaction between KCNB2 SNP rs1431656 (chromosome 8q13.3) and CACNB2 SNP rs7076100 (chromosome 10p12.33) (pointwise P = 0.00002; global P = 0.02) was observed in the Finnish case-control sample. We conclude that common variants of moderate effect size in ion transport genes do not play a major role in susceptibility to common migraine within these European populations, although there is some evidence for epistatic interaction between potassium and calcium channel genes, KCNB2 and CACNB2. Multiple rare variants or trans-regulatory elements of these genes are not ruled out.
- Subjects :
- Adult
Male
Migraine without Aura
Adolescent
Genotype
Single-nucleotide polymorphism
Biology
Polymorphism, Single Nucleotide
White People
03 medical and health sciences
Young Adult
0302 clinical medicine
Gene Frequency
Genetics
medicine
SNP
Humans
Child
Molecular Biology
Allele frequency
Gene
Genetics (clinical)
Familial hemiplegic migraine
Finland
030304 developmental biology
Aged
Demography
Aged, 80 and over
0303 health sciences
Ion Transport
KCNE2
General Medicine
Articles
Middle Aged
medicine.disease
Migraine with aura
Migraine
Genes
Case-Control Studies
biology.protein
Female
medicine.symptom
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....1286c426e7ec196395b5fcc2591eaca7