基于孟德尔随机化的自杀未遂与维生素D关系的研究

One of the worst things WHO has to face is the increase of suicide rate and the threaten to people health. Then, it is very necessary to study related factors with suicide for its prevention and control. Suicide is now understood as a multidimensional disorder, which results from a complex interaction of biological, psychological and socio- environmental factors. Recent studies have shown that almost every national suicide rate peaks in spring or spring and summer, overlapping with the low level of vitamin D in the same season, which could improve the function of people's brains. Therefore, the hypothesis which vitamin D might play a role in suicide requires evidences support. On the basis of our previous work, Mendelian randomization analysis approach which could resolve confounding and limit reverse causation problems appeared in observational epidemiological studies, will be applied in a hospital-based pair matching case-control study. The new cases of suicide attempters in population will continue to be chosen as cases and persons who meet the requirements will be chosen as controls in Shandong Province. Each study subjects need to be analyzed the serum level of vitamin D and four single nucleotide polymorphisms previously shown to be involved in vitamin D metabolism. Then, the distribution of vitamin D and four single nucleotide polymorphisms should be described and compared between suicidal attempters and controls. By means of instrumental variable models, the relationship between vitamin D and suicide could be identified based on the two relationships: vitamin D-single nucleotide polymorphism; attempted suicide-single nucleotide polymorphism. Consequently, the study might prove the hypothesis on the correlation between vitamin D and suicide. Furthermore, it might provide new clues for preventing suicide in the world.

WHO指出因全球自杀率上升、严重危害人类健康，故研究自杀相关因素对防制自杀十分必要。自杀由生物、心理和社会等因素相互作用所导致。研究发现自杀率存在春/春夏季高于其他季节的特征，也发现具有改善脑部功能作用的维生素D于春季时在人体内含量较低。故VD在自杀中可能具有作用的假设亟需验证。本项目拟在前期工作的基础上，基于可解决观察流行病学研究中混杂和反向因果关系影响的孟德尔随机化分析，继续选取山东省一般人群中新发自杀未遂病例和对照，进行配对病例对照研究；检测两组体内维生素D水平和四种代谢相关基因的基因多态性；描述、比较维生素D和四种代谢相关基因的基因多态性在自杀未遂者、对照者中的分布；计算基因型-维生素D、基因型-自杀未遂的关联效应后利用工具变量模型推导维生素D和自杀未遂间的关联效应，以验证维生素D与自杀未遂相关性的假说，为自杀防制措施提供新的生物学证据。

自杀一直是全球重要的公众健康问题之一。WHO呼吁：采取可行的措施以预防和控制自杀。预防和控制自杀的关键在于能否辨识自杀的影响因素。参与自杀研究的学者广泛认同自杀系心理、社会和环境等因素共同作用的结果。研究发现自杀率存在春/春夏季高于其他季节的特征，也发现具有改善脑部功能作用的维生素D（VD）于春季时在人体内含量较低。故VD在自杀中可能具有作用的假设亟需验证。本研究基于可解决观察流行病学研究中混杂和反向因果关系影响的孟德尔随机化分析，选取山东省一般人群中新发自杀未遂病例和对照，进行配对病例对照研究；检测两组体内维生素D水平和四种代谢相关基因的基因多态性；描述、比较维生素D和四种代谢相关基因的基因多态性在自杀未遂者、对照者中的分布；分析基因型-维生素D、基因型-混杂因素的相关性后，以孟德尔随机化方法探讨了维生素D和自杀未遂间的相关性。结果表明，血清中维生素D含量病例组为25.31±8.75nmol/L，对照组为24.13±7.37nmol/L（P>0.05）。调整采血时间后，则病例组血清中维生素D含量为26.01±9.17nmol/L，略低于对照组的26.84±7.67nmol/L（P>0.05）。高纬度区的自杀未遂者血清中维生素D含量为22.30±9.78nmol/L，显著低于低纬度区自杀未遂者26.80±8.87nmol/L（P<0.05）。冬季及春季自杀行为的发生占66.08%，高于夏季及秋季（P<0.05）。春季维生素D水平22.11±9.13nmol/L，显著低于其他季节（P<0.05）。病例组心理扭力异常、抑郁者、简易应对技能差者、SCID功能大体评定差者的构成均高于对照组（P<0.05），冲动异常者低于对照组（P<0.05）。不同心理状况异常者与无异常者血清中维生素D含量情况比较结果显示除冲动、焦虑外，其余均为病例组低于对照组（P>0.05）。证明了本研究中所选4种SNP满足进行孟德尔随机化分析的要求并调整混杂因素后，Cox回归分析与孟德尔随机化分析结果均未能证实维生素D与自杀未遂之间的相关性。本结论可能受样本量小的影响较大，今后将进一步扩大样本量并力争获得大数据支持，进一步探讨维生素D与自杀未遂之间的相关性。