By Elena Moro
For August 2016 we have selected: Gormley P, Anttila V, Winsvold BS, et al. Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine. Nature Genetics 2016 June 20;doi: 10.1038/ng.3598.
Migraine is a worldwide common, disabling, and costly disease. Its pathophysiology has been related to either a primary vascular dysfunction or a primary neuronal dysfunction with secondary vascular involvement. Despite a clear genetic component, only 13 genome-wide significant risk loci have been so far recognized for the main forms of migraine.
A meta-analysis of 22 genome-wide association (GWA) studies was conducted in 59,674 migraine subjects and 316,078 controls to identify new susceptibility loci. Data were collected from six tertiary headache clinics and 27 population-based cohorts, in collaboration with the International Headache Genetics Consortium. The association analyses were performed using logistic regression on the assigned marker dosage, and association results were combined in an inverse-variance weighted fixed-effects meta-analysis. Forty-four genome-wide significant single-nucleotide polymorphism (SNP) associations were identified, that mapped to 38 genomic loci for the prevalent forms of migraine. A secondary analysis found seven significantly associated genomic loci for migraine without aura but not for migraine with aura. Characterization of the associated loci showed that some genes’ expression was higher in some tissues compared to others. Specifically, four genes were more expressed in the brain and other eight genes more in the vascular tissues. Gene expression enrichment was stronger in the cardiovascular system and in the digestive system. Moreover, set enrichment analysis identified nine vascular-related biological function categories.
“This large genetic study has found several migraine-associated genes that are involved in both arterial and smooth muscle function, thus supporting the role of the vascular dysfunction on migraine pathophysiology.” says Prof. Ivan Milanov, University Neurological Hospital “St. Naum”, Medical University of Sofia, Bulgaria. “However, specific loci for migraine without aura but not for migraine with aura were also identified, probably related to the lack of statistical power due to smaller sample size of migraine with aura subjects.”
The other nominee for the August paper of the month is:
Andlauer TFM, Buck D, Antony G, et al. Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation. Sci Adv 2016;2:e1501678. A genome-wide association study on multiple sclerosis (MS) susceptibility was performed in 4,888 German patients and 10,395 controls. The authors found four new loci outside the major histocompatibility complex region that mapped to genes involved in regulatory processes of the immune system. These results support the hypothesis that epigenetic mechanisms are important for MS susceptibility.
