W70. ASSOCIATION BETWEEN MBD5 GENE AND DEPRESSIVE SYMPTOMATOLOGY IN MEXICAN POPULATION: RESULTS FROM MXGDAR/ENCODAT COHORT

• Published in: European neuropsychopharmacology Vol. 75; p. S141
• Main Authors: Camarena, Beatriz, Sanabrais-Jiménez, Marco Antonio, García, Alejandro Aguilar, Genis, Alma, Villatoro-Velazquez, Jorge Ameth, Fleiz-Bautista, Clara, Bustos-Gamiño, Marycarmen, Martínez-Magaña, José, Nicolini, Humberto, Medina-Mora, Maria Elena
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.10.2023
• ISSN: 0924-977X; 1873-7862
• DOI: 10.1016/j.euroneuro.2023.08.257

Anxiety and depression are the most prevalent comorbid psychiatric traits resulting in a substantial disease burden, greater mortality, losing up to 4 years of life compared with the general population. It has been demonstrated that 39% of patients with generalized anxiety disorder also meet diagnostic criteria for depression. Several studies have stablished that depression and anxiety share a genetic liability. In addition, a study provided additional evidence showing a high genetic overlap between depression and anxiety symptoms (Thorp et al., 2021), which is consistent with the genetic overlap between major depressive and anxiety disorders. The aim of this study was explored in a Mexican cohort the association between the 76 candidate genes previously reported and subjects with depressive and anxiety symptoms. The sample included a total of 2012 individuals (1419 females and 593 males) from the Mexican Genomic Database for Addiction Research (MxGDAR/Encodat). Depressive and anxiety lifetime symptomatology were evaluated using the DI-PAD screening questionnaire. Of the total sample, 198 showed anxiety symptoms, 266 depressive symptoms, 66 anxiety and depressive symptoms, and 1482 healthy controls. The sample was genotyped with the commercial microarray PsychArray BeadChip. We selected and analyzed 707 SNPs of 76 candidate genes previously associated with anxiety and depressive symptoms (Thorp et al., 2021). Quality control and association analysis were performed with the PLINK2 program. Bonferroni correction for multiple testing was applied (p < 8.21 × 10-5) and adjusted for age, sex, and three genetic principal components. The analysis of 609 variants after quality control showed association between the rs7578002 (p=5.85 × 10-5) and rs1234428 (p=8.15 × 10-5) of MBD5 and depressive symptoms after adjusting for age, sex, and the three genetic principal components. Interestingly, the rs2437092 (p=3.89 × 10-5) and exm2266254 (p=5.01 × 10-5) of LAMA gene; and rs11066591 (p=4.06 × 10-5) of MYO1H gene showed association in subjects with depressive and anxiety symptoms; however, none were significant after adjustment for age, sex, and the three genetic principal components. Our study replicated the findings of association between the MBD5 and depressive symptoms. MBD5 gene codify to methyl-CpG-binding domain protein 5 and has been associated with depressive and anxiety symptoms in a sample of UK Biobank and 23andMe cohort. MBD5 belongs to the MBD family binding preferentially to methylated DNA and recruiting protein complexes containing transcriptional repressors, generating gene silencing that could be involved in the development of depressive symptoms in Mexican population. Our findings should be analyzed in a larger sample of patients with depressive and anxiety disorders.