Molecular genetic overlap between migraine and major depressive disorder

Autor: Yang, Yuanhao, Zhao, Huiying, Boomsma, Dorret I, Smith, George Davey, Esko, Tonu, Hansen, Thomas Folkmann, Ikram, M. Arfan, Paraskevi, Christofidou, Strachan, David P., Wessman, Maija, Gormley, Padhraig, Anttila, Verneri, Winsvold, Bendik S., Palta, Priit, Pers, Tune H., Farh, Kai-How, Cuenca-Leon, Ester, Muona, Mikko, Furlotte, Nicholas A., Kurth, Tobias, Ingason, Andres, McMahon, George, Ligthart, Lannie, Kallela, Mikko, Freilinger, Tobias M., Ran, Caroline, Gordon, Scott G., Stam, Anine H., Steinberg, Stacy, Borck, Guntram, Koiranen, Markku, Quaye, Lydia, Adams, Hieab H. H., Lehtimäki, Terho, Sarin, Antti-Pekka, Wedenoja, Juho, Hinds, David A., Buring, Julie E., Schürks, Markus, Ridker, Paul M., Hrafnsdottir, Maria Gudlaug, Stefansson, Hreinn, Ring, Susan M., Hottenga, Jouke-Jan, Penninx, Brenda W. J. H., Färkkilä, Markus, Artto, Ville, Kaunisto, Mari, Vepsäläinen, Salli, Malik, Rainer, Heath, Andrew C., Madden, Pamela A. F., Martin, Nicholas G., Montgomery, Grant W, Kurki, Mitja I, Kals, Mart, Mägi, Reedik, Pärn, Kalle, Hämäläinen, Eija, Huang, Hailiang, Byrnes, Andrea E., Franke, Lude, Huang, Jie, Stergiakouli, Evie, Lee, Phil H., Sandor, Cynthia, Webber, Caleb, Cader, Zameel, Muller-Myhsok, Bertram, Schreiber, Stefan, Meitinger, Thomas, Eriksson, Johan G., Salomaa, Veikko, Heikkilä, Kauko, Loehrer, Elizabeth, Uitterlinden, Andre G., Hofman, Albert, van Duijn, Cornelia M., Cherkas, Lynn, Pedersen, Linda M., Stubhaug, Audun, Nielsen, Christopher S., Männikkö, Minna, Mihailov, Evelin, Milani, Lili, Göbel, Hartmut, Esserlind, Ann-Louise, Christensen, Anne Francke, Werge, Thomas, Kaprio, Jaakko, Aromaa, Arpo J., Raitakari, Olli, Spector, Tim, Järvelin, Marjo-Riitta, Metspalu, Andres, Kubisch, Christian, Ferrari, Michel D., Belin, Andrea C., Dichgans, Martin, Zwart, John-Anker, Stefansson, Kari, Eriksson, Nicholas, Daly, Mark J., Neale, Benjamin M., Olesen, Jes, Chasman, Daniel I., Nyholt, Dale R., Palotie, Aarno, van den Maagdenberg, Arn M. J. M., Terwindt, Gisela M.
Přispěvatelé: Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, Epidemiology, Biological Psychology, APH - Methodology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: European Journal of Human Genetics
Boomsma, D I, Ligthart, L, Hottenga, J J, Penninx, B W J H & The International Headache Genetics Consortium 2018, ' Molecular genetic overlap between migraine and major depressive disorder ', European Journal of Human Genetics, vol. 26, no. 8, pp. 1202-1216 . https://doi.org/10.1038/s41431-018-0150-2
The International Headache Genetics Consortium 2018, ' Molecular genetic overlap between migraine and major depressive disorder ', European Journal of Human Genetics, vol. 26, no. 8, pp. 1202-1216 . https://doi.org/10.1038/s41431-018-0150-2
the International Headache Genetics Consortium, Yang, Y, Zhao, H, Boomsma, D I, Ligthart, L, Belin, A C, Smith, G D, Esko, T, Freilinger, T M, Hansen, T F, Ikram, M A, Kallela, M, Kubisch, C, Paraskevi, C, Strachan, D P, Wessman, M, Gormley, P, Anttila, V, Winsvold, B S, Palta, P, Esko, T, Pers, T H, Farh, K H, Cuenca-Leon, E, Muona, M, Furlotte, N A, Kurth, T, Ingason, A, McMahon, G, Ligthart, L, Terwindt, G M, Kallela, M, Freilinger, T M, Ran, C, Gordon, S G, Stam, A H, Steinberg, S, Borck, G, Koiranen, M, Quaye, L, Adams, H H H, Lehtimäki, T, Sarin, A P, Wedenoja, J, Hinds, D A, Buring, J E, Schürks, M, Ridker, P M, Ring, S M, Stergiakouli, E & Smith, G D 2018, ' Molecular genetic overlap between migraine and major depressive disorder ', European Journal of Human Genetics, vol. 26, no. 8, pp. 1202-1216 . https://doi.org/10.1038/s41431-018-0150-2
European Journal of Human Genetics, 26(8), 1202-1216. Nature Publishing Group
ISSN: 1018-4813
Popis: Migraine and major depressive disorder (MDD) are common brain disorders that frequently co-occur. Despite epidemiological evidence that migraine and MDD share a genetic basis, their overlap at the molecular genetic level has not been thoroughly investigated. Using single-nucleotide polymorphism (SNP) and gene-based analysis of genome-wide association study (GWAS) genotype data, we found significant genetic overlap across the two disorders. LD Score regression revealed a significant SNP-based heritability for both migraine (h2= 12%) and MDD (h2= 19%), and a significant cross-disorder genetic correlation (rG= 0.25; P = 0.04). Meta-analysis of results for 8,045,569 SNPs from a migraine GWAS (comprising 30,465 migraine cases and 143,147 control samples) and the top 10,000 SNPs from a MDD GWAS (comprising 75,607 MDD cases and 231,747 healthy controls), implicated three SNPs (rs146377178, rs672931, and rs11858956) with novel genome-wide significant association (PSNP≤ 5 × 10−8) to migraine and MDD. Moreover, gene-based association analyses revealed significant enrichment of genes nominally associated (Pgene-based≤ 0.05) with both migraine and MDD (Pbinomial-test= 0.001). Combining results across migraine and MDD, two genes, ANKDD1B and KCNK5, produced Fisher’s combined gene-based P values that surpassed the genome-wide significance threshold (PFisher’s-combined≤ 3.6 × 10−6). Pathway analysis of genes with PFisher’s-combined≤ 1 × 10−3suggested several pathways, foremost neural-related pathways of signalling and ion channel regulation, to be involved in migraine and MDD aetiology. In conclusion, our study provides strong molecular genetic support for shared genetically determined biological mechanisms underlying migraine and MDD.
Databáze: OpenAIRE
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