葡萄糖和胰岛素相关特征、2 型糖尿病与精神分裂症风险：一项孟德尔随机研究。
Glucose and Insulin-Related Traits, Type 2 Diabetes and Risk of Schizophrenia: A Mendelian Randomization Study.
机构信息
The Affiliated Hospital of Qingdao University, The Biomedical Sciences Institute of Qingdao University (Qingdao Branch of SJTU Bio-X Institutes), Qingdao University, No. 16 Jiangsu Road, Qingdao 266003, PR China; Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), the Collaborative Innovation Center for Brain Science, Shanghai Jiao Tong University, No. 1954 Huashan Road, Shanghai 200030, PR China; Institute of Social Cognitive and Behavioral Sciences, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Shanghai 200240, PR China; Institute of Neuropsychiatric Science and Systems Biological Medicine, Shanghai Jiao Tong University, No. 1954 Huashan Road, Shanghai 200030, PR China.
Key Laboratory of Pathobiology, Ministry of Education, Jilin University, No. 45 Chaoyang Xi Road, Changchun 130021, PR China; College of Basic Medical Sciences, Jilin University, No. 126 Xinmin Street, Changchun 130021, PR China; National Institute of Digestive, Diabetes and Kidney Diseases, National Institutes of Health, 445 N 5th St, Phoenix, AZ 85004, USA.
出版信息
EBioMedicine. 2018 Aug;34:182-188. doi: 10.1016/j.ebiom.2018.07.037. Epub 2018 Aug 9.
BACKGROUND
The link between schizophrenia and diabetes mellitus is well established by observational studies; however, the cause-effect relationship remains unclear.
METHODS
Here, we conducted Mendelian randomization analyses to assess a causal relationship of the genetic variants related to elevated fasting glucose levels, hemoglobin A (HbA), fasting insulin levels, and type 2 diabetes with the risk of schizophrenia. The analyses were performed using summary statistics obtained for the variants identified from the genome-wide association meta-analyses of fasting glucose levels (up to 133,010 individuals), HbA (up to 153,377 individuals), fasting insulin levels (up to 108,557 individuals), type 2 diabetes (up to 659,316 individuals), and schizophrenia (up to 108,341 individuals). The association between each variant and schizophrenia was weighted by its association with each studied condition, and estimates were combined using an inverse-variance weighted meta-analysis.
FINDINGS
Using information from thirteen variants related to fasting insulin levels, the causal effect of fasting insulin levels increases (per 1-SD) on the risk of schizophrenia was estimated at an odds ratio (OR) of 2·33 (p = 0·001), which is consistent with findings from the observational studies. The fasting glucose associated single nucleotide polymorphisms (SNPs) had no effect on the risk of schizophrenia in Europeans and East Asians (p > 0·05). Nonsignificant effects on the risk of schizophrenia was observed with raised HbA and type 2 diabetes, and consistent estimates were obtained across different populations.
INTERPRETATION
Our results suggest a causal role of elevated fasting insulin levels in schizophrenia pathogenesis.
背景
观察性研究充分证实了精神分裂症与糖尿病之间存在关联；然而，其因果关系仍不清楚。
方法
本研究采用孟德尔随机化分析来评估与空腹血糖升高、糖化血红蛋白（HbA）、空腹胰岛素水平和 2 型糖尿病相关的遗传变异与精神分裂症风险之间的因果关系。使用全基因组关联荟萃分析中获得的与空腹血糖（多达 133010 人）、HbA（多达 153377 人）、空腹胰岛素水平（多达 108557 人）、2 型糖尿病（多达 659316 人）和精神分裂症（多达 108341 人）相关的变异的汇总统计数据进行了分析。每个变异与精神分裂症的关联由其与每个研究条件的关联加权，使用逆方差加权荟萃分析合并估计值。
发现
使用与空腹胰岛素水平相关的 13 个变异的信息，空腹胰岛素水平每升高 1 个标准差（SD），精神分裂症的风险估计比值比（OR）为 2.33（p=0.001），这与观察性研究的结果一致。在欧洲人和东亚人中，与空腹葡萄糖相关的单核苷酸多态性（SNP）对精神分裂症的风险没有影响（p＞0.05）。升高的 HbA 和 2 型糖尿病对精神分裂症的风险没有显著影响，且在不同人群中得到了一致的估计。
解释
我们的研究结果表明，空腹胰岛素水平升高与精神分裂症发病机制之间存在因果关系。
Zotero 插件