Common susceptibility variant associated with migraine

3 September 2010

Migraine is a common neurologic disorder characterised by recurrent attacks of severe and disabling headache. According to the NHS, migraines affect one in four women and one in 12 men in the UK. Although genetic factors are known to play a part in migraines, no genetic or molecular markers have been established for this disease so far.
Recently, researchers from the UK Wellcome Trust Sanger Institute have collaborated with scientists from across Europe to carry out a two stage genome –wide association study (GWAS) to identify variants associated with common forms of migraine [Anttila et al (2010) Nature Genetics doi:10.1038/ng.652]. In the ‘discovery stage’ of the study, 3,279 migraine cases and 10,747 healthy matched controls from specialized headache clinics in Europe were genotyped for over half a million single nucleotide polymorphisms (SNPs); in the ‘replication stage’, a further 3,202 cases and 40,062 controls were similarly genotyped. They identified a SNP (rs1835740) located on chromosome 8q22.1 which is significantly associated with migraine, (OR=1.18 with a p-value of 1.69×10−11 in meta-analysis) and is estimated to explain 1.5-2.5% of the genetic variance. The marker is located between two genes (MTDH and PGCP) which are strongly associated with the production of the neurotransmitter glutamate, which itself is known to be important in the pathophysiology of migraine. This provides indirect evidence of the role of rs1835740 SNP in the mechanism of migraine attacks due to excess accumulation of glutamate in the junction of nerve cells. An investigation of the impact of rs1835740 on gene expression levels also indicated a significant correlation with transcript levels of MTDH.
Comments: The authors state that this is “the first robust genetic association to migraine”. In order to examine the effect of this new variant on chromosome 8, especially in different migraine subgroups, further large scale studies in broader population–based migraine cohorts are essential. Once the underlying pathways are better understood, and more genetic variants responsible for migraine are discovered, it may be possible to design new treatments for this devastating condition.