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Molecular genetic overlap between migraine and major depressive disorder
- Source :
- 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
- Publication Year :
- 2018
- Publisher :
- Springer International Publishing, 2018.
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
Netherlands Twin Register (NTR)
Linkage disequilibrium
Migraine Disorders
Medizin
Single-nucleotide polymorphism
Genome-wide association study
Polymorphism, Single Nucleotide
Article
Linkage Disequilibrium
03 medical and health sciences
0302 clinical medicine
Potassium Channels, Tandem Pore Domain
SDG 3 - Good Health and Well-being
Genotype
Databases, Genetic
Genetics
medicine
SNP
Humans
Genetics (clinical)
Depressive Disorder, Major
business.industry
medicine.disease
Comorbidity
Ankyrin Repeat
030104 developmental biology
Migraine
Major depressive disorder
business
030217 neurology & neurosurgery
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- ISSN :
- 10184813
- Database :
- OpenAIRE
- Journal :
- 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
- Accession number :
- edsair.doi.dedup.....950ea06bbd691cb84376056bc246b2d3