Genetic Variants Associated With Subjective Cognitive Decline in Patients With Migraine

Abstract

The genetic association between subjective cognitive decline (SCD) and migraine comorbidity remains unclear. Furthermore, single nucleotide polymorphisms (SNP) associated with SCD have not been identified previously. Migraineurs were genotyped using an Affymetrix array. The correlation between different SNP variants in migraineurs with or without SCD and non-migraine controls was investigated. Migraineurs with or without SCD were further divided for the analysis of relevant SNP variants linked to migraine with aura (MA), migraine without aura (MoA), episodic migraine (EM), and chronic migraine (CM). Significant connectivity between SNPs and clinical indices in migraineurs and non-migraine controls with SCD were assessed using multivariate regression analysis. The rs144191744 SNP was found in migraineurs (p = 3.19E-08), EM (p = 1.34E-07), and MoA(p = 7.69E-07) with and without SCD. The T allele frequency for rs144191744 in TGFBR3 was 0.0054 and 0.0445 in migraineurs with and without SCD (odds ratio, 0.12), respectively. rs2352564, rs6089473 in CDH4, rs112400385 in ST18, rs4488224 and rs17111203 in ARHGAP29 SNPs were found, respectively, in non-migraineurs (p = 4.85E-06, p = 8.28E-06), MoA (p = 3.13E-07), and CM subgroups (p = 1.05E-07, 6.24E-07) with and without SCD. Rs144191744 closely relates to SCD with the all-migraine group and the EM and MoA subgroups. In conclusion, rs144191744 in TGFBR3 was significantly associated with SCD in migraineurs, especially in the EM, MoA, and female patient subgroups. Furthermore, three SNPs (rs112400385, rs4488224, and rs17111203) were associated with SCD in migraineurs but not in non-migraine controls.

Genome-wide Association Studies of REST Gene Associated Neurological Diseases/traits with Related Single Nucleotide Polymorphisms

“…The REST gene is related with not only neurodevelopmental such as ADHD but also it is associated with ASD, psychiatric disorder such as bipolar disorder and schizophrenia [ 15 ]. It also is related to neurodegenerative such as cognitive impairment and as AD and subjective cognitive impairment with migraine headache [ 16 ]. Meanwhile, other mapped genes were exposed to these diseases which could be directly or indirectly related to REST.…”

Understanding the Role of CDH4 in Multiple System Atrophy Brain

“…Increases in CDH4 expression have been detected in brain-derived microvascular endothelial cells in Huntington's disease [13]. And, a SNP in CDH4 has been identified in patients with subjective cognitive decline [14]. CDH2, which shares 74% homology with CDH4 [15], has been implicated in Alzheimer's disease pathology, with protein fragments present in diseased brain [16].…”