Author(s): O’Connor E.; Campbell C.; Southgate L.; Trembath R.; Yip H.Y.; Houlden H.; Hostettler I.C.; Silver N.; Giffin N.J.; Cader M.Z.; Ahmed F.; Davies B.; Matharu M.

Source: Cephalalgia; Sep 2019; vol. 39 (no. 1); p. 1

Publication Date: Sep 2019

Publication Type(s): Conference Abstract

Abstract:Objective: The genetic variation predisposing patients to CH remains elusive. The majority of genetic studies have been association studies in candidate genes with a putative role in CH. We sought to evaluate reported genetic associations with CH, through examination of SNPs in the genes HCRTR2 (rs2653349 and rs3122156), CLOCK (rs12649507) and ADH4 (rs1126671). Also to examine previous GWAS findings in an independent cohort including analysis of candidates rs12668955 within ADCYAP1R1, rs1006417 upstream of the LRFN5 gene and rs147564881 in MME. Method(s): A multicentre study involving six headache centres in the UK between 2016 and 2019. Patients diagnosed with episodic or chronic CH by a neurologist in concordance with the ICHD3b criteria were recruited to the study. DNA was extracted from peripheral blood or saliva and genotyped using the Illumina Infinium Global Screening Array. SNPs of interest were identified and screened for association. Result(s): Overall, approximately 880 cases and 5,000 controls were screened for previously associated variants in candidate genes. Genotype analysis did not identify a statistically significant association between any previously implicated candidate variant and cluster headache Conclusion(s): This is the largest cohort to date examining genetic associations with CH. Our findings do not support previous reports identifying associations between CH and variants in plausible candidates. Whilst this may represent population-specific effects, these findings highlight the importance of independent replication studies, using sufficiently powered datasets and a hypothesis-free approach. It outlines the requirement for multi-centre, collaborative efforts for patient recruitment in future studies.

Database: EMBASE