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Current Pharmacogenomics and Personalized Medicine


ISSN (Print): 1875-6921
ISSN (Online): 1875-6913

Research Article

Generalized Analysis of Open Genetic Databases Reveals New Associations with Migraine

Author(s): Aliya Yakubova* and Albert A. Rizvanov

Volume 20, Issue 3, 2023

Published on: 12 January, 2024

Page: [165 - 176] Pages: 12

DOI: 10.2174/0118756921286656231219095417

Price: $65


Background: Migraine is one of the most common diseases that significantly impairs the quality of life. This condition has a pronounced genetic component. Genes responsible for the development of monogenic forms of hemiplegic migraine have already been identified, and the search for genetic associations with common migraine and its subtypes continues.

Objective: The aim of this study was to search for new potential genetic markers of migraine by analyzing available open genetic databases.

Methods: The analysis included databases such as ClinVar, GWAS Catalog, UK Biobank and FinnGen. In all databases, the keyword "migraine" was used to search for migraineassociated variants. Genetic variants with clinical annotations "pathogenic" and "likely pathogenic" were selected from the variants in the ClinVar database. From other databases, variants with an association significance level of p ≤ 5×10-8 were chosen.

Results: A total of 112 genetic variants associated with migraine were identified. After excluding polymorphisms known from previous migraine studies, it was found that 45 genetic variants were identified for the first time.

Conclusion: These variants belong to various functional groups, including ion channels, enzymes, receptors, and regulatory proteins, confirming the current understanding of the polygenic nature of migraine. Identifying new genetic associations with migraine can contribute to a better understanding of its pathogenesis and open new possibilities for diagnosis and the development of more effective treatment strategies for this condition.

Keywords: Migraine, genetic database, polymorphism, genetic variant, genetic marker, regulatory proteins.

Graphical Abstract
Chasman DI, Schürks M, Anttila V, et al. Genome-wide association study reveals three susceptibility loci for common migraine in the general population. Nat Genet 2011; 43(7): 695-8.
[] [PMID: 21666692]
van den Maagdenberg AMJM, Nyholt DR, Anttila V. Novel hypotheses emerging from GWAS in migraine? J Headache Pain 2019; 20(1): 5.
[] [PMID: 30634909]
Mulder EJ, van Baal C, Gaist D, et al. Genetic and environmental influences on migraine: A twin study across six countries. Twin Res 2003; 6(5): 422-31.
[] [PMID: 14624726]
Russell MB, Olesen J. The genetics of migraine without aura and migraine with aura. Cephalalgia 1993; 13(4): 245-8.
[] [PMID: 8374938]
Russell M, Iselius L, Olesen J. Inheritance of migraine investigated by complex segregation analysis. Hum Genet 1995; 96(6): 726-30.
[] [PMID: 8522335]
Stewart SM, Lam TH, Betson CL, Wong CM, Wong AM. A prospective analysis of stress and academic performance in the first two years of medical school. Med Educ 1999; 33(4): 243-50.
[] [PMID: 10336754]
Kuca B, Silberstein SD, Wietecha L, Berg PH, Dozier G, Lipton RB. Lasmiditan is an effective acute treatment for migraine. Neurology 2018; 91(24): e2222-32.
[] [PMID: 30446595]
Lipton RB, Dodick DW, Ailani J, et al. Effect of ubrogepant vs placebo on pain and the most bothersome associated symptom in the acute treatment of migraine: the ACHIEVE II randomized clinical trial. JAMA 2019; 322(19): 1887-98.
[] [PMID: 31742631]
Charles A, Pozo-Rosich P. Targeting calcitonin generelated peptide: A new era in migraine therapy. Lancet 2019; 394(10210): 1765-74.
[] [PMID: 31668411]
Lipton RB, Stewart WF, Simon D. Medical consultation for migraine: Results from the American migraine study. Headache 1998; 38(2): 87-96.
[] [PMID: 9529763]
Ophoff RA, Terwindt GM, Vergouwe MN, et al. Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4. Cell 1996; 87(3): 543-52.
[] [PMID: 8898206]
Fusco MD, Marconi R, Silvestri L, et al. Haploinsufficiency of ATP1A2 encoding the Na+/K+ pump α2 subunit associated with familial hemiplegic migraine type 2. Nat Genet 2003; 33(2): 192-6.
[] [PMID: 12539047]
Dichgans M, Freilinger T, Eckstein G, et al. Mutation in the neuronal voltage-gated sodium channel SCN1A in familial hemiplegic migraine. Lancet 2005; 366(9483): 371-7.
[] [PMID: 16054936]
Dasdemir S, Cetinkaya Y, Gencer M, Ozkok E, Aydin M, Cakmakoglu B. Cox-2 gene variants in migraine. Gene 2013; 518(2): 292-5.
[] [PMID: 23357220]
Borroni B, Brambilla C, Liberini P, et al. Functional serotonin 5–HTTLPR polymorphism is a risk factor for migraine with aura. J Headache Pain 2005; 6(4): 182-4.
[] [PMID: 16362658]
Rafiei A, Abedini M, Hosseini SH, Hosseini-Khah Z, Bazrafshan B, Tehrani M. Toll like receptor-4 896A/G gene variation, a risk factor for migraine headaches. Iran J Immunol 2012; 9(3): 159-67.
[PMID: 23023380]
Juhasz G, Lazary J, Chase D, et al. Variations in the cannabinoid receptor 1 gene predispose to migraine. Neurosci Lett 2009; 461(2): 116-20.
[] [PMID: 19539700]
Cetinkaya Y, Dasdemir S, Gencer M, et al. DNA repair gene variants in migraine. Genet Test Mol Biomarkers 2014; 18(8): 568-73.
[] [PMID: 24892639]
Erdal N, Herken H, Yilmaz M, Erdal E, Bayazit YA. The A218C polymorphism of tryptophan hydroxylase gene and migraine. J Clin Neurosci 2007; 14(3): 249-51.
[] [PMID: 17194593]
Shin HE, Han SJ, Lee KS, Park JW. Polymorphism of the glutamate transporter protein EAAT2 and migraine transformation into chronic daily headache. J Clin Neurol 2011; 7(3): 143-7.
[] [PMID: 22087208]
Kowa H, Fusayasu E, Ijiri T, et al. Association of the insertion/deletion polymorphism of the angiotensin I-converting enzyme gene in patients of migraine with aura. Neurosci Lett 2005; 374(2): 129-31.
[] [PMID: 15644278]
García-Martín E, Martínez C, Serrador M, et al. Alcohol dehydrogenase 2 genotype and risk for migraine. Headache 2010; 50(1): 85-91.
[] [PMID: 19486361]
García-Martín E, Martínez C, Serrador M, et al. Paraoxonase 1 (PON1) polymorphisms and risk for migraine. J Neurol 2010; 257(9): 1482-5.
[] [PMID: 20407783]
Kondratieva NS, Azimova JE, Sergeev AV, et al. Association of polymorphisms of genes of NO synthases and migraine in Moscow. Cephalalgia 2015; 35(6S): 266.
Horasanlı B, Ataç FB, Çöven İ Karakurum Goksel B, Benli S. Angiotensin I-converting enzyme gene (I/D) polymorphism in patients with migraine. Headache 2013; 53(1): 161-4.
[] [PMID: 23278516]
Kara I, Ozkok E, Aydin M, et al. Combined effects of ACE and MMP-3 polymorphisms on migraine development. Cephalalgia 2007; 27(3): 235-43.
[] [PMID: 17381556]
Menon S, Lea RA, Roy B, et al. The human μ-opioid receptor gene polymorphism (A118G) is associated with head pain severity in a clinical cohort of female migraine with aura patients. J Headache Pain 2012; 13(7): 513-9.
[] [PMID: 22752568]
Ghosh J, Joshi G, Pradhan S, Mittal B. Investigation of TNFA 308G > A and TNFB 252G > A polymorphisms in genetic susceptibility to migraine. J Neurol 2010; 257(6): 898-904.
[] [PMID: 20035431]
Lemos C, Mendonça D, Pereira-Monteiro J, et al. BDNF and CGRP interaction: Implications in migraine susceptibility. Cephalalgia 2010; 30(11): 1375-82.
[] [PMID: 20959432]
Gonçalves FM, Martins-Oliveira A, Speciali JG, et al. Vascular endothelial growth factor genetic polymorphisms and haplotypes in women with migraine. DNA Cell Biol 2010; 29(7): 357-62.
[] [PMID: 20482220]
Pizza V, Bisogno A, Lamaida E, et al. Migraine and coronary artery disease: an open study on the genetic polymorphism of the 5, 10 methylenetetrahydrofolate (MTHFR) and angiotensin I-converting enzyme (ACE) genes. Cent Nerv Syst Agents Med Chem 2010; 10(2): 91-6.
[] [PMID: 20518725]
Nyholt DR, LaForge KS, Kallela M, et al. A high-density association screen of 155 ion transport genes for involvement with common migraine. Hum Mol Genet 2008; 17(21): 3318-31.
[] [PMID: 18676988]
Motaghi M, Haghjooy Javanmard S, Haghdoost F, et al. Relationship between vitamin D receptor gene polymorphisms and migraine without aura in an Iranian population. BioMed Res Int 2013; 2013: 1-6.
[] [PMID: 23984350]
Palmirotta R, Barbanti P, Ialongo C, et al. Progesterone receptor gene (PROGINS) polymorphism correlates with late onset of migraine. DNA Cell Biol 2015; 34(3): 208-12.
[] [PMID: 25494303]
Rainero I, Grimaldi LME, Salani G, et al. Apolipoprotein E gene polymorphisms in patients with migraine. Neurosci Lett 2002; 317(2): 111-3.
[] [PMID: 11755252]
Rainero I, Grimaldi LME, Salani G, et al. Association between the tumor necrosis factor- -308 G/A gene polymorphism and migraine. Neurology 2004; 62(1): 141-3.
[] [PMID: 14718719]
Tropeano M, Wöber-Bingöl Ç, Karwautz A, et al. Association analysis of STX1A gene variants in common forms of migraine. Cephalalgia 2012; 32(3): 203-12.
[] [PMID: 22250207]
Rodriguez-Acevedo AJ, Smith RA, Roy B, et al. Genetic association and gene expression studies suggest that genetic variants in the SYNE1 and TNF genes are related to menstrual migraine. J Headache Pain 2014; 15(1): 62.
[] [PMID: 25315199]
Sutherland HG, Buteri J, Menon S, et al. Association study of the calcitonin gene-related polypeptide-alpha (CALCA) and the receptor activity modifying 1 (RAMP1) genes with migraine. Gene 2013; 515(1): 187-92.
[] [PMID: 23237777]
Zandifar A, Iraji N, Taheriun M, Tajaddini M, Javanmard SH. Association of the long pentraxin PTX3 gene polymorphism (rs3816527) with migraine in an Iranian population. J Neurol Sci 2015; 349(1-2): 185-9.
[] [PMID: 25604633]
Maher BH, Griffiths LR. Identification of molecular genetic factors that influence migraine. Mol Genet Genomics 2011; 285(6): 433-46.
[] [PMID: 21519858]
Yakubova A, Davidyuk Y, Tohka J, et al. Searching for predictors of migraine chronification: A Pilot Study of 1911A>G Polymorphism of TRPV1 gene in episodic versus chronic migraine. J Mol Neurosci 2021; 71(3): 618-24.
[] [PMID: 32827294]
Yakubova A. The Effect of TRPV1 rs8065080 single nucleotide polymorphism on the risk of migraine chronification Advances in Health and Disease. New York: Nova Science Publishers, Inc. 2023; Vol. 68: pp. 209-19.
Yakubova A, Shagimardanova E, Grigoryeva T, et al. Genomic screening of chronic migraine patients identified genes linked to drug and endogenous substances metabolism. Bionanoscience 2022; 12(1): 154-9.
Landrum MJ, Lee JM, Benson M, et al. ClinVar: Improving access to variant interpretations and supporting evidence. Nucleic Acids Res 2018; 46(D1): D1062-7.
[] [PMID: 29165669]
Buniello A, MacArthur JAL, Cerezo M, et al. The NHGRI-EBI GWAS Catalog of published genome-wide association studies, targeted arrays and summary statistics 2019. Nucleic Acids Res 2019; 47(D1): D1005-12.
[] [PMID: 30445434]
Sudlow C, Gallacher J, Allen N, et al. UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med 2015; 12(3): e1001779.
[] [PMID: 25826379]
Hautakangas H, Winsvold BS, Ruotsalainen SE, et al. Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles. Nat Genet 2022; 54(2): 152-60.
[] [PMID: 35115687]
Azimova YE. Migraine: features of pathogenesis as the basis for personalized therapy Dissertation work for the degree of the Doctor of Medical Sciences 2022.
Anttila V, Stefansson H, Kallela M, et al. Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1. Nat Genet 2010; 42(10): 869-73.
[] [PMID: 20802479]
Freilinger T, Anttila V, de Vries B, et al. Genome-wide association analysis identifies susceptibility loci for migraine without aura. Nat Genet 2012; 44(7): 777-82.
[] [PMID: 22683712]
Gormley P, Anttila V, Winsvold BS, et al. Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine. Nat Genet 2016; 48(8): 856-66.
[] [PMID: 27322543]
Zhao H, Eising E, de Vries B, et al. Gene-based pleiotropy across migraine with aura and migraine without aura patient groups. Cephalalgia 2016; 36(7): 648-57.
[] [PMID: 26660531]
Meng W, Adams MJ, Hebert HL, Deary IJ, McIntosh AM, Smith BH. A genome-wide association study finds genetic associations with broadly-defined headache in uk biobank (N = 223,773). EBioMedicine 2018; 28: 180-6.
[] [PMID: 29397368]
Pelzer N, Haan J, Stam AH, et al. Clinical spectrum of hemiplegic migraine and chances of finding a pathogenic mutation. Neurology 2018; 90(7): e575-82.
[] [PMID: 29343472]
de Vries B, Freilinger T, Vanmolkot KRJ, et al. Systematic analysis of three FHM genes in 39 sporadic patients with hemiplegic migraine. Neurology 2007; 69(23): 2170-6.
[] [PMID: 18056581]
Lee ST, Chu K, Jung KH, et al. Decreased number and function of endothelial progenitor cells in patients with migraine. Neurology 2008; 70(17): 1510-7.
[] [PMID: 18354079]

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