Syncope in Migraine: A Genome-Wide Association Study Revealing Distinct Genetic Susceptibility Variants Across Subtypes
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background and Purpose Syncope is characterized by the temporary loss of consciousness and is commonly associated with migraine. However, the genetic factors that contribute to this association are not well understood. This study investigated the specific genetic loci that make patients with migraine more susceptible to syncope as well as the genetic factors contributing to syncope and migraine comorbidity in a Han Chinese population in Taiwan. Methods A genome-wide association study was applied to 1,724 patients with migraine who visited a tertiary hospital in Taiwan. The patients were genotyped using the Affymetrix Axiom Genome-Wide TWB 2.0 array and categorized into the following subgroups based on migraine type: episodic migraine, chronic migraine, migraine with aura, and migraine without aura. Multivariate regression analyses were used to assess the relationships between specific single-nucleotide polymorphisms (SNPs) and the clinical characteristics in patients with syncope and migraine comorbidity. Results In patients with migraine, SNPs were observed to be associated with syncope. In particular, the rs797384 SNP located in the intron region of LOC102724945 was associated with syncope in all patients with migraine. Additionally, four SNPs associated with syncope susceptibility were detected in the nonmigraine control group, and these SNPs differed from those in the migraine group, suggesting distinct underlying mechanisms. Furthermore, the rs797384 variant in the intron region of LOC102724945 was associated with the score on the Beck Depression Inventory. Conclusions The novel genetic loci identified in this study will improve our understanding of the genetic basis of syncope and migraine comorbidity.
Abstract
Background and Purpose Syncope is characterized by the temporary loss of consciousness and is commonly associated with migraine. However, the genetic factors that contribute to this association are not well understood. This study investigated the specific genetic loci that make patients with migraine more susceptible to syncope as well as the genetic factors contributing to syncope and migraine comorbidity in a Han Chinese population in Taiwan. Methods A genome-wide association study was applied to 1,724 patients with migraine who visited a tertiary hospital in Taiwan. The patients were genotyped using the Affymetrix Axiom Genome-Wide TWB 2.0 array and categorized into the following subgroups based on migraine type: episodic migraine, chronic migraine, migraine with aura, and migraine without aura. Multivariate regression analyses were used to assess the relationships between specific single-nucleotide polymorphisms (SNPs) and the clinical characteristics in patients with syncope and migraine comorbidity. Results In patients with migraine, SNPs were observed to be associated with syncope. In particular, the rs797384 SNP located in the intron region of LOC102724945 was associated with syncope in all patients with migraine. Additionally, four SNPs associated with syncope susceptibility were detected in the nonmigraine control group, and these SNPs differed from those in the migraine group, suggesting distinct underlying mechanisms. Furthermore, the rs797384 variant in the intron region of LOC102724945 was associated with the score on the Beck Depression Inventory. Conclusions The novel genetic loci identified in this study will improve our understanding of the genetic basis of syncope and migraine comorbidity.
참고문헌 (41)
- Goadsby PJ, "Pathophysiology of migraine : a disorder of sensory processing", Physiol Rev, 97, pp.553~622 (2017)
- Brignole M, "2018 ESC Guidelines for the diagnosis and management of syncope", Eur Heart J, 39, pp.1883~1948 (2018)
- Curfman D, "Syncopal migraine", Clin Auton Res, 22, pp.17~23 (2012)
- Kuan AS, "Risk factors and psychological impact of syncope in migraine patients", Cephalalgia, 39, pp.1838~1846 (2019)
- Silva VPR, "Vestibular migraine", Arq Neuropsiquiatr, 80, pp.232~237 (2022)
- Thijs RD, "Syncope in migraine : the population-based CAMERA study", Neurology, 66, pp.1034~1037 (2006)
- Piovesan EJ, "Episodic migraine associated with postural orthostatic tachycardia syndrome and vasovagal syncope : migraine triggers neuromediated syncope", Arq Neuropsiquiatr, 66, pp.77~79 (2008)
- Hautakangas H, "Genome-wide analysis of 102, 084 migraine cases identifies 123 risk loci and subtype-specific risk alleles", Nat Genet, 54, pp.152~160 (2022)
- Aegisdottir HM, "Genetic variants associated with syncope implicate neural and autonomic processes", Eur Heart J, 44, pp.1070~1080 (2023)
- Daas A, "Familial vasovagal syncope associated with migraine", Pediatr Neurol, 40, pp.27~30 (2009)
- Headache Classification Committee of the International Headache Society(IHS), "The International Classification of Headache Disorders, 3rd edition", Cephalalgia, 38, pp.1~211 (2018)
- Stewart WF, "Development and testing of the Migraine Disability Assessment(MIDAS)Questionnaire to assess headache-related disability", Neurology, 56(6 Suppl 1), pp.S20~S28 (2001)
- Zigmond AS, "The hospital anxiety and depression scale", Acta Psychiatr Scand, 67, pp.361~370 (1983)
- Beck AT, "An inventory for measuring depression", Arch Gen Psychiatry, 4, pp.561~571 (1961)
- Chang CC, "Second-generation PLINK : rising to the challenge of larger and richer datasets", Gigascience, 4, pp.s13742-015-0047-8~ (2015)
- O’Leary NA, "Reference sequence(RefSeq)database at NCBI : current status, taxonomic expansion, and functional annotation", Nucleic Acids Res, 44, pp.D733~D745 (2016)
- Wang K, "ANNOVAR : functional annotation of genetic variants from high-throughput sequencing data", Nucleic Acids Res, 38, pp.e164~ (2010)
- Chu A, "Comprehensive analysis of aberrantly expressed ceRNA network in gastric cancer with and without H. pylori infection", J Cancer, 10, pp.853~863 (2019)
- Liu YY, "PI3K", AKT signaling pathway activation in a rat model of migraine, 2017, pp.16, 4849~4854
- Malbouyres M, "Lack of the myotendinous junction marker col22a1 results in posture and locomotion disabilities in zebrafish", Matrix Biol, 109, pp.1~18 (2022)
- Mak AC, "Brief report : whole-exome sequencing for identification of potential causal variants for diffuse cutaneous systemic sclerosis", Arthritis Rheumatol, 68, pp.2257~2262 (2016)
- Cavestro C, "Migraine in systemic autoimmune diseases", Endocr Metab Immune Disord Drug Targets, 18, pp.124~134 (2018)
- Shen Y, "Uncovering the gene regulatory network of endothelial cells in mouse duchenne muscular dystrophy : insights from single-nuclei RNA sequencing analysis", Biology(Basel), 12, pp.422~ (2023)
- Linnemann A, "Myopodin is an F-actin bundling protein with multiple independent actin-binding regions", J Muscle Res Cell Motil, 34, pp.61~69 (2013)
- Perisic L, "Gene expression signatures, pathways and networks in carotid atherosclerosis", J Intern Med, 279, pp.293~308 (2016)
- Men X, "Genomic investigation of remission and relapse of psychotic depression treated with sertraline plus olanzapine : the STOP-PD II study", Neuropsychobiology, 82, pp.168~178 (2023)
- Schwedt TJ, "Endothelial dysfunction in migraine", Cephalalgia, 29, pp.997~1002 (2009)
- Grubb BP, "Neurocardiogenic syncope and related disorders of orthostatic intolerance", Circulation, 111, pp.2997~3006 (2005)
- Zhang X, "The role of NELL-1, a growth factor associated with craniosynostosis, in promoting bone regeneration", J Dent Res, 89, pp.865~878 (2010)
- Majerus PW, "Expression of inositol 1, 3, 4-trisphosphate 5", 6-kinase(ITPK1)and its role in neural tube defects, 2010, pp.50, 365~372
- Xiang Z, "Lnc GNG12-AS1knockdown suppresses glioma progression through the AKT", GSK-3β, Biosci Rep, pp.2020, 40[DOI]
- Gao J, "Wnt", β-catenin signaling in neural stem cell homeostasis and neurological diseases, 2021, pp.27, 58~72
- Yang YT, "DOCK7 interacts with TACC3 to regulate interkinetic nuclear migration and cortical neurogenesis", Nat Neurosci, 15, pp.1201~1210 (2012)
- Sarkar S, "FGFR3-TACC3 cancer gene fusions cause mitotic defects by removal of endogenous TACC3 from the mitotic spindle", Open Biol, 7, pp.170080~ (2017)
- Morey RA, "Genome-wide association study of subcortical brain volume in PTSD cases and trauma-exposed controls", Transl Psychiatry, 7, pp.1265~ (2017)
- Zhang P, "Protocadherin 11x regulates differentiation and proliferation of neural stem cell in vitro and in vivo", J Mol Neurosci, 54, pp.199~210 (2014)
- Hadji-Turdeghal K, "Genome-wide association study identifies locus at chromosome 2q32. 1 associated with syncope and collapse", Cardiovasc Res, 116, pp.138~148 (2020)
- Gay A, "Wnt signaling in cardiovascular disease : opportunities and challenges", Curr Opin Lipidol, 28, pp.387~396 (2017)
- Kumari A, "Regulation of microtubule stability by centrosomal proteins", IUBMB Life, 70, pp.602~611 (2018)
- Hayashi S, "Protocadherin-17 mediates collective axon extension by recruiting actin regulator complexes to interaxonal contacts", Dev Cell, 30, pp.673~687 (2014)
- Baum AE, "A genome-wide association study implicates diacylglycerol kinase eta(DGKH)and several other genes in the etiology of bipolar disorder", Mol Psychiatry, 13, pp.197~207 (2008)
