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dc.contributor.authorBacchelli, Elena
dc.contributor.authorCainazzo, Maria Michela
dc.contributor.authorCameli, Cinzia
dc.contributor.authorGuerzoni, Simona
dc.contributor.authorMartinelli, Angela
dc.contributor.authorZoli, Michele
dc.contributor.authorMaestrini, Elena
dc.contributor.authorPini, Luigi Alberto
dc.identifier.citationBacchelli , E , Cainazzo , M M , Cameli , C , Guerzoni , S , Martinelli , A , Zoli , M , Maestrini , E & Pini , L A 2016 , ' A genome-wide analysis in cluster headache points to neprilysin and PACAP receptor gene variants ' , Journal of Headache and Pain , vol. 17 , no. 1 , 114 .
dc.identifier.otherPURE: 248498914
dc.identifier.otherPURE UUID: 9fa74ebb-3a5e-434f-816f-d73276b4b46d
dc.identifier.otherScopus: 85003890232
dc.identifier.otherWOS: 000391849300001
dc.descriptionSupported by the Italian Ministry of Health (RF2009-1549619), University of Bologna (RFO).en
dc.description.abstractBackground : Cluster Headache (CH) is a severe primary headache, with a poorly understood pathophysiology. Complex genetic factors are likely to play a role in CH etiology; however, no confirmed gene associations have been identified. The aim of this study is to identify genetic variants influencing risk to CH and to explore the potential pathogenic mechanisms. Methods : We have performed a genome-wide association study (GWAS) in a clinically well-defined cohort of 99 Italian patients with CH and in a control sample of 360 age-matched sigarette smoking healthy individuals, using the Infinium PsychArray (Illumina), which combines common highly-informative genome-wide tag SNPs and exonic SNPs. Genotype data were used to carry out a genome-wide single marker case-control association analysis using common SNPs, and a gene-based association analysis focussing on rare protein altering variants in 745 candidate genes with a putative role in CH. Results : Although no single variant showed statistically significant association at the genome-wide threshold, we identified an interesting suggestive association (P = 9.1 × 10−6) with a common variant of the PACAP receptor gene (ADCYAP1R1). Furthermore, gene-based analysis provided significant evidence of association (P = 2.5 × 10−5) for a rare potentially damaging missense variant in the MME gene, encoding for the membrane metallo-endopeptidase neprilysin. Conclusions : Our study represents the first genome-wide association study of common SNPs and rare exonic variants influencing risk for CH. The most interesting results implicate ADCYAP1R1 and MME gene variants in CH susceptibility and point to a role for genes involved in pain processing. These findings provide new insights into the pathogenesis of CH that need further investigation and replication in larger CH samples.
dc.relation.ispartofJournal of Headache and Painen
dc.rights© The Author(s). 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.en
dc.subjectAssociation studies in geneticsen
dc.subjectCluster headacheen
dc.subjectGenome-Wide Association Studyen
dc.subjectMembrane metalloendopeptidase (MME)en
dc.subjectMissense mutationen
dc.subjectPituitary adenylate cyclase-activating polypeptide receptor (ADCYAP1R1)en
dc.subjectR Medicineen
dc.subjectRC0321 Neuroscience. Biological psychiatry. Neuropsychiatryen
dc.subjectClinical Neurologyen
dc.subjectAnesthesiology and Pain Medicineen
dc.titleA genome-wide analysis in cluster headache points to neprilysin and PACAP receptor gene variantsen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Medicineen
dc.description.statusPeer revieweden

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