Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
German Centre of Neurodegenerative Diseases (DZNE), Greifswald, Germany.
Genes Brain Behav. 2021 Jun;20(5):e12737. doi: 10.1111/gbb.12737. Epub 2021 May 12.
Genetic factors are assumed to contribute to memory performance, especially genes affecting the dopaminergic neurotransmission. We aimed to evaluate leading functional genetic variants of the dopamine system, Catechol-O-methyltransferase (COMT) SNP rs4680 and Brain-derived neurotropic factor (BDNF) SNP rs6265, previously found to be associated with memory performance. In two independent general population cohorts (total N = 5937) we investigated direct and interaction effects between COMT and BDNF SNPs on declarative memory performance. We found significant two-way interactions for COMT and BDNF in both cohorts but no direct genetic effects. Sensitivity analyses revealed that an interaction between COMT and BDNF was mainly carried by females. While direct associations of COMT and BDNF on memory have been reported previously, we could demonstrate that the interaction of COMT and BDNF is sex-dependent and more complex and needs further investigation. Our results could be demonstrated in two independent cohorts of valuable size.
遗传因素被认为对记忆表现有贡献，特别是影响多巴胺能神经传递的基因。我们旨在评估多巴胺系统的主要功能遗传变异，儿茶酚-O-甲基转移酶（COMT）SNP rs4680 和脑源性神经营养因子（BDNF）SNP rs6265，先前发现它们与记忆表现相关。在两个独立的一般人群队列（总共 N=5937）中，我们研究了 COMT 和 BDNF SNP 之间的直接和相互作用对陈述性记忆表现的影响。我们发现 COMT 和 BDNF 在两个队列中都存在显著的双向相互作用，但没有直接的遗传效应。敏感性分析表明，COMT 和 BDNF 之间的相互作用主要发生在女性中。虽然先前已经报道了 COMT 和 BDNF 对记忆的直接关联，但我们可以证明 COMT 和 BDNF 的相互作用是性别依赖性的，并且更复杂，需要进一步研究。我们的结果可以在两个具有重要规模的独立队列中得到证明。
