Cabrera-Mendoza Brenda, Martínez-Magaña José Jaime, Genis-Mendoza Alma Delia, Sarmiento Emmanuel, Ruíz-Ramos David, Tovilla-Zárate Carlos Alfonso, González-Castro Thelma Beatriz, Juárez-Rojop Isela Esther, García-de la Cruz Dulce Dajheanne, López-Armenta Mauro, Real Fernanda, García-Dolores Fernando, Flores Gonzalo, Vázquez-Roque Rubén Antonio, Lanzagorta Nuria, Escamilla Michael, Saucedo-Uribe Erasmo, Rodríguez-Mayoral Oscar, Jiménez-Genchi Janet, Castañeda-González Carlos, Roche-Bergua Andrés, Nicolini Humberto
Genomics of Psychiatric and Neurodegenerative Diseases Laboratory, National Institute of Genomic Medicine (INMEGEN), Mexico City, Mexico; PECEM, Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico.
Genomics of Psychiatric and Neurodegenerative Diseases Laboratory, National Institute of Genomic Medicine (INMEGEN), Mexico City, Mexico; Multidisciplinary Academic Division of Comalcalco, Juárez Autonomous University of Tabasco, Comalcalco, Tabasco, Mexico.
J Psychiatr Res. 2020 Apr;123:62-71. doi: 10.1016/j.jpsychires.2020.01.008. Epub 2020 Jan 29.
Suicidal behavior is result of the interaction of several contributors, including genetic and environmental factors. The integration of approaches considering the polygenic component of suicidal behavior, such as polygenic risk scores (PRS) and DNA methylation is promising for improving our understanding of the complex interplay between genetic and environmental factors in this behavior. The aim of this study was the evaluation of DNA methylation differences between individuals with high and low genetic burden for suicidality. The present study was divided into two phases. In the first phase, genotyping with the Psycharray chip was performed in a discovery sample of 568 Mexican individuals, of which 149 had suicidal behavior (64 individuals with suicidal ideation, 50 with suicide attempt and 35 with completed suicide). Then, a PRS analysis based on summary statistics from the Psychiatric Genomic Consortium was performed in the discovery sample. In a second phase, we evaluated DNA methylation differences between individuals with high and low genetic burden for suicidality in a sub-sample of the discovery sample (target sample) of 94 subjects. We identified 153 differentially methylated sites between individuals with low and high-PRS. Among genes mapped to differentially methylated sites, we found genes involved in neurodevelopment (CHD7, RFX4, KCNA1, PLCB1, PITX1, NUMBL) and ATP binding (KIF7, NUBP2, KIF6, ATP8B1, ATP11A, CLCN7, MYLK, MAP2K5). Our results suggest that genetic variants might increase the predisposition to epigenetic variations in genes involved in neurodevelopment. This study highlights the possible implication of polygenic burden in the alteration of epigenetic changes in suicidal behavior.
自杀行为是多种因素相互作用的结果，包括遗传和环境因素。综合考虑自杀行为多基因成分的方法，如多基因风险评分（PRS）和DNA甲基化，有望增进我们对该行为中遗传和环境因素复杂相互作用的理解。本研究的目的是评估自杀倾向遗传负担高和低的个体之间的DNA甲基化差异。本研究分为两个阶段。在第一阶段，对568名墨西哥个体的发现样本进行了Psycharray芯片基因分型，其中149人有自杀行为（64人有自杀意念，50人有自杀未遂，35人自杀身亡）。然后，在发现样本中基于精神基因组学联盟的汇总统计数据进行了PRS分析。在第二阶段，我们在94名受试者的发现样本子样本（目标样本）中评估了自杀倾向遗传负担高和低的个体之间的DNA甲基化差异。我们在低PRS和高PRS个体之间鉴定出153个差异甲基化位点。在映射到差异甲基化位点的基因中，我们发现了参与神经发育（CHD7、RFX4、KCNA1、PLCB1、PITX1、NUMBL）和ATP结合（KIF7、NUBP2、KIF6、ATP8B1、ATP11A、CLCN7、MYLK、MAP2K5）的基因。我们的结果表明，遗传变异可能会增加参与神经发育的基因发生表观遗传变异的易感性。本研究强调了多基因负担在自杀行为表观遗传变化改变中的可能影响。
