Department of Psychiatry and Psychotherapy, University Medicine Greifswald, 17475 Greifswald, Germany.
German Centre for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, 17475 Greifswald, Germany.
Int J Mol Sci. 2023 Jan 6;24(2):1120. doi: 10.3390/ijms24021120.
The aim of this study was to disentangle the effects of various genetic factors on hippocampal subfield volumes using three different approaches: a biologically driven candidate gene approach, a hypothesis-free GWAS approach, and a polygenic approach, where AD risk alleles are combined with a polygenic risk score (PRS). The impact of these genetic factors was investigated in a large dementia-free general population cohort from the Study of Health in Pomerania (SHIP, = 1806). Analyses were performed using linear regression models adjusted for biological and environmental risk factors. Hippocampus subfield volume alterations were found for ε4, Val, and L allele carriers. In addition, we were able to replicate GWAS findings, especially for rs17178139 (), rs1861979 (), rs7873551 (), and rs572246240 (). Interaction analyses between the significant SNPs as well as the PRS for AD revealed no significant results. Our results confirm that hippocampal volume reductions are influenced by genetic variation, and that different variants reveal different association patterns that can be linked to biological processes in neurodegeneration. Thus, this study underlines the importance of specific genetic analyses in the quest for acquiring deeper insights into the biology of hippocampal volume loss, memory impairment, depression, and neurodegenerative diseases.
本研究旨在使用三种不同方法，即基于生物学的候选基因方法、无假设的 GWAS 方法和多基因方法，来区分各种遗传因素对海马亚区体积的影响。在来自波美拉尼亚健康研究（SHIP）的一个无痴呆的大型一般人群队列（ = 1806）中，我们调查了这些遗传因素的影响。使用经过生物学和环境风险因素调整的线性回归模型进行分析。我们发现 ε4、Val 和 L 等位基因携带者的海马亚区体积发生了改变。此外，我们还能够复制 GWAS 发现，特别是 rs17178139()、rs1861979()、rs7873551()和 rs572246240()。对显著 SNP 以及 AD 的 PRS 进行的交互分析没有发现显著结果。我们的结果证实，海马体积的减少受遗传变异的影响，不同的变体显示出不同的关联模式，这些模式可能与神经退行性变中的生物学过程有关。因此，这项研究强调了特定遗传分析在深入了解海马体积减少、记忆障碍、抑郁和神经退行性疾病的生物学方面的重要性。
