维生素D与SIRT1基因交互作用对老年认知功能影响的队列研究

The prevalence of cognitive impairment among Chinese older adults is rising year by year, which brings heavy burden to families and society. At present, the etiology of cognitive impairment is still unclear and the treatment is far from satisfactory. In this concern, early diagnosis and the precision prevention of cognitive impairment under the varied genetic background is of great demand. By utilizing the data of Chinese longitudinal Healthy Longevity Survey 2011-2021, this proposal aims to evaluate the screening value and the intervention potential of the vitamin D by identifying the causal relationship between vitamin D impairment and cognitive impairment, the SNP alleles of vitamin D deficiency were detected through genome wide association study and were implemented us instrumental variables to identify the above causal relationship with Mendelian randomization analyses. This proposal also designed to study the interaction effect on elderly cognitive impairment between vitamin D and SIRT1 genotypes through Gene by Environment interaction analyses under the Nested case-control study frame, to effectively prevent cognitive decline and improve cognitive function by developing the vitamin D-relevant nutrition intervention on the varied SIRT1 allele carriers, thus to provide novel thoughts and directions on the precision management and intervention on cognitive impairment in Chinese older adults.

我国老年人群认知功能障碍患病率较高且呈逐年上升趋势，给家庭及社会带来沉重负担。目前认知功能障碍的发病机制不明，治疗效果欠佳，因此需提高老年人群认知功能障碍的早期识别能力并针对不同遗传背景进行精准预防。本研究使用中国老年健康影响因素调查2011-2021数据，通过全基因组关联分析方法筛选维生素D缺乏相关SNP位点，将其作为工具变量通过孟德尔随机化方法识别维生素D缺乏与认知功能障碍的因果联系，从而评估维生素D在老年认知功能障碍中的筛查价值和干预潜力；本研究通过巢式病例对照研究设计下的遗传-环境交互作用分析方法，研究维生素D与SIRT1基因对于老年认知功能障碍是否存在交互作用及其大小与方向，探索不同SIRT1基因位点携带者如何通过维生素D相关营养干预从而有效预防认知衰退和改善认知功能，为我国老年认知健康精准管理及有效干预提供新思路和新方向。

我国老年人群认知功能障碍患病率较高且呈逐年上升趋势，给家庭及社会带来沉重负担。目前认知功能障碍的发病机制不明，治疗效果欠佳，因此需提高老年人群认知功能障碍的早期识别能力并针对不同遗传背景进行精准预防。本项目基于前期工作基础，使用中国老年健康影响因素调查2011-2021数据，通过全基因组关联分析方法筛选维生素D缺乏相关SNP位点，将其作为工具变量通过孟德尔随机化方法识别维生素D缺乏与认知功能障碍的因果联系，从而评估维生素D在老年认知功能障碍中的筛查价值和干预潜力；本研究通过前瞻性队列研究设计下的遗传-环境交互作用分析方法，研究维生素D及其他炎症衰老相关生物标志物与SIRT1基因对于老年认知功能障碍是否存在交互作用及其大小与方向（JCEM 2020; Front Immunol 2021），探索不同SIRT1基因位点携带者如何通过维生素D相关营养干预从而有效预防认知衰退和改善认知功能（Environ Health 2021），为我国老年认知健康精准管理及有效干预提供新思路和新方向（Lancet 2022; Lancet Public Health; Lancet Healthy Longevity 2022）。