Genome-wide association susceptibility loci for cluster headache support a role for inflammation in the pathophysiology
Abstract
Background: Recent genetic findings have broadened the perspectives of cluster headache pathophysiology. Genes identified by genome wide association studies are likely to be involved in the pathophysiological mechanisms underlying the disease. In this study, we performed validation and characterization of eight loci corresponding to nine genes identified in previous genome wide association studies.
Methods: Genetic loci were validated by means of a case-control study using TaqMan genotyping in 671 individuals, and a meta-analysis using previously genotyped data. Pyrosequencing methylation analysis and reverse transcription quantitative PCR gene expression studies was performed in a subset of individuals with cluster headache and healthy controls.
Results: Genetic associations were found with functional variants in two genes; FHL5 and MERTK. The minor allele of the FHL5 variant rs2273621 was associated with an increased risk of cluster headache in the genotyped samples (odds ratio = 1.42, P = 0.03) and in a meta-analysis (odds ratio = 1.29, confidence interval: 1.09-1.52), and the minor allele of the rs2230515 variant in MERTK was associated with lower risk in the meta-analysis (odds ratio = 0.69, confidence interval: 0.52-0.92). Methylation analysis further revealed altered methylation status of MERTK. Moreover, changes in relative gene expression were found for several candidate genes: a decrease in the mRNA expression of DUSP10 (P < 0.001), CAPN2 (P < 0.001), UFL1 (P <…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 671 participants or records.
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