Gene-based pleiotropy across migraine with aura and migraine without aura patient groups
| Autor: | Dale R. Nyholt, Rainer Malik, Gisela M. Terwindt, Grant W. Montgomery, Lannie Ligthart, Christian Kubisch, Nicholas G. Martin, Mikko Kallela, Dorret I. Boomsma, M. Arfan Ikram, Arn M. J. M. van den Maagdenberg, Tobias Freilinger, Bendik S. Winsvold, Kari Stefansson, Stefan Schreiber, John-Anker Zwart, Hreinn Stefansson, Lydia Quaye, Bertram Müller-Myhsok, Aarno Palotie, Arpo Aromas, Boukje de Vries, Thomas Meitinger, Michel D. Ferrari, M. Wessman, Huiying Zhao, Johan G. Eriksson, L. S. Vijfhuizen, Tobias Kurth, Anine H. Stam, Michael Alexander, Else Eising, Martin Dichgans, Cornelia M. van Duijn, Daniel I. Chasman, Verneri Anttila |
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| Přispěvatelé: | Clinicum, Neurologian yksikkö, Department of Neurosciences, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, Diabetes and Obesity Research Program, Research Programs Unit, Institute for Molecular Medicine Finland, Research Programme of Molecular Medicine, Aarno Palotie / Principal Investigator, Genomics of Neurological and Neuropsychiatric Disorders, EMGO+ - Quality of Care, Biological Psychology, Epidemiology, Neurology, Radiology & Nuclear Medicine |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Netherlands Twin Register (NTR) Male Migraine without Aura Receptors Neuropeptide Aura Migraine with Aura Genome-wide association study 3124 Neurology and psychiatry genome-wide PATHWAY 0302 clinical medicine POPULATION Migraine Association Gene-based Genome-wide Pleiotropy Genetic Pleiotropy General Medicine SDG 10 - Reduced Inequalities CANCER 3. Good health NOTCH Female medicine.symptom STROKE gene-based Adult medicine.medical_specialty SUSCEPTIBILITY LOCI Article 03 medical and health sciences aura pleiotropy REVEALS medicine Humans Genetic Predisposition to Disease GENOME-WIDE ASSOCIATION Psychiatry CORTICAL SPREADING DEPRESSION RECEPTOR business.industry association 3112 Neurosciences medicine.disease Migraine with aura 030104 developmental biology Pleiotropy (drugs) International Classification of Headache Disorders Neurology (clinical) business 030217 neurology & neurosurgery Genome-Wide Association Study |
| Zdroj: | CEPHALALGIA Cephalalgia Zhao, H, Eising, E, de Vries, B, Vijfhuizen, L S, Anttila, V, Winsvold, B S, Kurth, T, Stefansson, H, Kallela, M, Malik, R, Stam, A H, Arfan Ikram, M, Ligthart, L, Freilinger, T, Alexander, M, Müller-Myhsok, B, Schreiber, S, Meitinger, T, Aromas, A, Eriksson, J G, Boomsma, D I, van Duijn, C M, Zwart, J A, Quaye, L, Kubisch, C, Dichgans, M, Wessman, M, Stefansson, K, Chasman, D I, Palotie, A, Martin, N G, Montgomery, G W, Ferrari, M D, Terwindt, G M, van den Maagdenberg, A M J M & Nyholt, DR 2016, ' Gene-based pleiotropy across migraine with aura and migraine without aura patient groups ', Cephalalgia, vol. 36, no. 7, pp. 648-657 . https://doi.org/10.1177/0333102415591497 Cephalalgia 36, 648-657 (2016) Cephalalgia, 36(7), 648-657. SAGE Publications Ltd Cephalalgia, 36(7), 648-657 |
| ISSN: | 0333-1024 |
| DOI: | 10.1177/0333102415591497 |
| Popis: | Introduction It is unclear whether patients diagnosed according to International Classification of Headache Disorders criteria for migraine with aura (MA) and migraine without aura (MO) experience distinct disorders or whether their migraine subtypes are genetically related. Aim Using a novel gene-based (statistical) approach, we aimed to identify individual genes and pathways associated both with MA and MO. Methods Gene-based tests were performed using genome-wide association summary statistic results from the most recent International Headache Genetics Consortium study comparing 4505 MA cases with 34,813 controls and 4038 MO cases with 40,294 controls. After accounting for non-independence of gene-based test results, we examined the significance of the proportion of shared genes associated with MA and MO. Results We found a significant overlap in genes associated with MA and MO. Of the total 1514 genes with a nominally significant gene-based p value ( pgene-based ≤ 0.05) in the MA subgroup, 107 also produced pgene-based ≤ 0.05 in the MO subgroup. The proportion of overlapping genes is almost double the empirically derived null expectation, producing significant evidence of gene-based overlap (pleiotropy) ( pbinomial-test = 1.5 × 10–4). Combining results across MA and MO, six genes produced genome-wide significant gene-based p values. Four of these genes ( TRPM8, UFL1, FHL5 and LRP1) were located in close proximity to previously reported genome-wide significant SNPs for migraine, while two genes, TARBP2 and NPFF separated by just 259 bp on chromosome 12q13.13, represent a novel risk locus. The genes overlapping in both migraine types were enriched for functions related to inflammation, the cardiovascular system and connective tissue. Conclusions Our results provide novel insight into the likely genes and biological mechanisms that underlie both MA and MO, and when combined with previous data, highlight the neuropeptide FF-amide peptide encoding gene ( NPFF) as a novel candidate risk gene for both types of migraine. |
| Databáze: | OpenAIRE |
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