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17-06-2012 | Genetics | Article

Four genetic loci linked to migraine without aura

Abstract

Free abstract

MedWire News: A genome-wide association study (GWAS) has identified several genetic loci associated with migraine without aura, the most common migraine type.

In total, six genes were identified, including four loci that have never been identified before. Two additional genes were found and, although not new, their identification confirms their role in migraine without aura based on previous studies.

Two specific loci, MEF2D and TGFBR2, "showed convincing association in the replication stage and genome-wide significance levels in the combined meta-analysis," report Tobias Freilinger (University of Munich, Germany) and colleagues.

Previous GWAS studies identified a migraine susceptibility locus on chromosome 8q22, close to MTDH, in migraine patients with aura, as well as at three other loci, but there are limited data on genes that predispose individuals to migraine without aura.

In the current analysis, published in Nature Genetics, the researchers studied 2326 Dutch and German individuals with migraine without aura and 4580 matched controls.

The group studied single nucleotide polymorphisms (SNPs) from 12 different gene loci.

The locus at 1q22 contained six SNPs that were associated with genome-wide significance in the discovery stage of the GWAS. Two SNPs, rs1050316 and rs3790455, were studied further and the associations successfully replicated.

The associated SNPs were located within the MEFD2 gene. The MEFD2 protein is a transcription factor that is highly expressed in the brain, note the researchers.

"A role for MEF2D dysregulation in migraine is also plausible given that several MEF2 transcriptional targets have been associated with other neurological disorders, such as epilepsy," they write.

The locus at 3p24 contained the SNP rs7640543, which reached genome-wide significance in the discovery and replication analyses. This SNP is located upstream of TGFBR2, a gene that encodes for a protein involved in the regulation of cell proliferation and differentiation.

The association of two other loci, PHACTR1 and ASTN2, were weaker and should be confirmed in additional studies, write Freilinger and colleagues.

In addition, TRPM8 and LRP1, previously linked with migraine, were confirmed as markers.

The researchers say that next steps will include functional studies to identify the underlying molecular pathways responsible, studies that will be needed to determine treatment targets for this common brain disorder.

By MedWire Reporters

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