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Molecular genetic overlap between migraine and major depressive disorder

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Molecular genetic overlap between migraine and major depressive disorder. / Yang, Yuanhao; Zhao, Huiying; Boomsma, Dorret I; Ligthart, Lannie; Belin, Andrea C; Smith, George Davey; Esko, Tonu; Freilinger, Tobias M; Hansen, Thomas Folkmann; Ikram, M Arfan; Kallela, Mikko; Kubisch, Christian; Paraskevi, Christofidou; Strachan, David P; Wessman, Maija; van den Maagdenberg, Arn M J M; Terwindt, Gisela M; Nyholt, Dale R; International Headache Genetics Consortium.

in: EUR J HUM GENET, Jahrgang 26, Nr. 8, 08.2018, S. 1202-1216.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Yang, Y, Zhao, H, Boomsma, DI, Ligthart, L, Belin, AC, Smith, GD, Esko, T, Freilinger, TM, Hansen, TF, Ikram, MA, Kallela, M, Kubisch, C, Paraskevi, C, Strachan, DP, Wessman, M, van den Maagdenberg, AMJM, Terwindt, GM, Nyholt, DR & International Headache Genetics Consortium 2018, 'Molecular genetic overlap between migraine and major depressive disorder', EUR J HUM GENET, Jg. 26, Nr. 8, S. 1202-1216. https://doi.org/10.1038/s41431-018-0150-2

APA

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., van den Maagdenberg, A. M. J. M., Terwindt, G. M., Nyholt, D. R., & International Headache Genetics Consortium (2018). Molecular genetic overlap between migraine and major depressive disorder. EUR J HUM GENET, 26(8), 1202-1216. https://doi.org/10.1038/s41431-018-0150-2

Vancouver

Yang Y, Zhao H, Boomsma DI, Ligthart L, Belin AC, Smith GD et al. Molecular genetic overlap between migraine and major depressive disorder. EUR J HUM GENET. 2018 Aug;26(8):1202-1216. https://doi.org/10.1038/s41431-018-0150-2

Bibtex

@article{68b3d61f3f75450cbfa5da6a5441e382,
title = "Molecular genetic overlap between migraine and major depressive disorder",
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 × 10-3 suggested 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.",
keywords = "Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural",
author = "Yuanhao Yang and Huiying Zhao and Boomsma, {Dorret I} and Lannie Ligthart and Belin, {Andrea C} and Smith, {George Davey} and Tonu Esko and Freilinger, {Tobias M} and Hansen, {Thomas Folkmann} and Ikram, {M Arfan} and Mikko Kallela and Christian Kubisch and Christofidou Paraskevi and Strachan, {David P} and Maija Wessman and {van den Maagdenberg}, {Arn M J M} and Terwindt, {Gisela M} and Nyholt, {Dale R} and {International Headache Genetics Consortium}",
year = "2018",
month = aug,
doi = "10.1038/s41431-018-0150-2",
language = "English",
volume = "26",
pages = "1202--1216",
journal = "EUR J HUM GENET",
issn = "1018-4813",
publisher = "NATURE PUBLISHING GROUP",
number = "8",

}

RIS

TY - JOUR

T1 - Molecular genetic overlap between migraine and major depressive disorder

AU - Yang, Yuanhao

AU - Zhao, Huiying

AU - Boomsma, Dorret I

AU - Ligthart, Lannie

AU - Belin, Andrea C

AU - Smith, George Davey

AU - Esko, Tonu

AU - Freilinger, Tobias M

AU - Hansen, Thomas Folkmann

AU - Ikram, M Arfan

AU - Kallela, Mikko

AU - Kubisch, Christian

AU - Paraskevi, Christofidou

AU - Strachan, David P

AU - Wessman, Maija

AU - van den Maagdenberg, Arn M J M

AU - Terwindt, Gisela M

AU - Nyholt, Dale R

AU - International Headache Genetics Consortium

PY - 2018/8

Y1 - 2018/8

N2 - 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 × 10-3 suggested 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.

AB - 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 × 10-3 suggested 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.

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

KW - Research Support, N.I.H., Extramural

U2 - 10.1038/s41431-018-0150-2

DO - 10.1038/s41431-018-0150-2

M3 - SCORING: Journal article

C2 - 29995844

VL - 26

SP - 1202

EP - 1216

JO - EUR J HUM GENET

JF - EUR J HUM GENET

SN - 1018-4813

IS - 8

ER -