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A genome-wide analysis in cluster headache points to neprilysin and PACAP receptor gene variants
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dc.contributor.author | Bacchelli, Elena | |
dc.contributor.author | Cainazzo, Maria Michela | |
dc.contributor.author | Cameli, Cinzia | |
dc.contributor.author | Guerzoni, Simona | |
dc.contributor.author | Martinelli, Angela | |
dc.contributor.author | Zoli, Michele | |
dc.contributor.author | Maestrini, Elena | |
dc.contributor.author | Pini, Luigi Alberto | |
dc.date.accessioned | 2016-12-22T16:30:23Z | |
dc.date.available | 2016-12-22T16:30:23Z | |
dc.date.issued | 2016-12-13 | |
dc.identifier.citation | Bacchelli , 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 . https://doi.org/10.1186/s10194-016-0705-y | en |
dc.identifier.issn | 1129-2369 | |
dc.identifier.other | PURE: 248498914 | |
dc.identifier.other | PURE UUID: 9fa74ebb-3a5e-434f-816f-d73276b4b46d | |
dc.identifier.other | Scopus: 85003890232 | |
dc.identifier.other | WOS: 000391849300001 | |
dc.identifier.uri | https://hdl.handle.net/10023/10007 | |
dc.description | Supported by the Italian Ministry of Health (RF2009-1549619), University of Bologna (RFO). | en |
dc.description.abstract | Background : 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.language.iso | eng | |
dc.relation.ispartof | Journal of Headache and Pain | en |
dc.rights | © The Author(s). 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), 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.subject | Association studies in genetics | en |
dc.subject | Cluster headache | en |
dc.subject | Genome-Wide Association Study | en |
dc.subject | Membrane metalloendopeptidase (MME) | en |
dc.subject | Missense mutation | en |
dc.subject | Neprylisin | en |
dc.subject | Pituitary adenylate cyclase-activating polypeptide receptor (ADCYAP1R1) | en |
dc.subject | R Medicine | en |
dc.subject | RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry | en |
dc.subject | Clinical Neurology | en |
dc.subject | Anesthesiology and Pain Medicine | en |
dc.subject | DAS | en |
dc.subject.lcc | R | en |
dc.subject.lcc | RC0321 | en |
dc.title | A genome-wide analysis in cluster headache points to neprilysin and PACAP receptor gene variants | en |
dc.type | Journal article | en |
dc.description.version | Publisher PDF | en |
dc.contributor.institution | University of St Andrews. School of Medicine | en |
dc.identifier.doi | https://doi.org/10.1186/s10194-016-0705-y | |
dc.description.status | Peer reviewed | en |
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