Su Mei-Hsin, Lai Rou-Yi, Lin Yen-Feng, Chen Chia-Yen, Feng Yen-Chen A, Hsiao Po-Chang, Wang Shi-Heng
Department of Occupational Safety and Health, College of Public Health, China Medical University, Taichung, Taiwan.
Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan.
Schizophrenia (Heidelb). 2022 Sep 9;8(1):72. doi: 10.1038/s41537-022-00281-5.
Cigarette smoking has been suggested to be associated with the risk of schizophrenia in observational studies. A significant causal effect of smoking on schizophrenia has been reported in European populations using the Mendelian randomization approach; however, no evidence of causality was found in participants from East Asia. Using Taiwan Biobank (TWBB), we conducted genome-wide association studies (GWAS) to identify susceptibility loci for smoking behaviors, including smoking initiation (N = 79,989) and the onset age (N = 15,582). We then meta-analyzed GWAS from TWBB and Biobank Japan (BBJ) with the total sample size of 245,425 for smoking initiation and 46,000 for onset age of smoking. The GWAS for schizophrenia was taken from the East Asia Psychiatric Genomics Consortium, which included 22,778 cases and 35,362 controls. We performed a two-sample Mendelian randomization to estimate the causality of smoking behaviors on schizophrenia in East Asia. In TWBB, we identified one locus that met genome-wide significance for onset age. In a meta-analysis of TWBB and BBJ, we identified two loci for smoking initiation. In Mendelian randomization, genetically predicted smoking initiation (odds ratio (OR) = 4.00, 95% confidence interval (CI) = 0.89-18.01, P = 0.071) and onset age (OR for a per-year increase = 0.96, 95% CI = 0.91-1.01, P = 0.098) were not significantly associated with schizophrenia; the direction of effect was consistent with European Ancestry samples, which had higher statistical power. These findings provide tentative evidence consistent with a causal role of smoking on the development of schizophrenia in East Asian populations.
在观察性研究中，吸烟被认为与精神分裂症风险相关。在欧洲人群中，采用孟德尔随机化方法报告了吸烟对精神分裂症有显著因果效应；然而，在东亚参与者中未发现因果关系的证据。利用台湾生物银行（TWBB），我们进行了全基因组关联研究（GWAS），以确定吸烟行为的易感基因座，包括开始吸烟（N = 79,989）和开始吸烟年龄（N = 15,582）。然后，我们对TWBB和日本生物银行（BBJ）的GWAS进行了荟萃分析，开始吸烟的总样本量为245,425，开始吸烟年龄的总样本量为46,000。精神分裂症的GWAS数据来自东亚精神病基因组学联盟，包括22,778例病例和35,362例对照。我们进行了两样本孟德尔随机化，以估计东亚地区吸烟行为对精神分裂症的因果关系。在TWBB中，我们确定了一个达到全基因组显著性的开始吸烟年龄基因座。在TWBB和BBJ的荟萃分析中，我们确定了两个开始吸烟的基因座。在孟德尔随机化分析中，基因预测的开始吸烟（优势比（OR）= 4.00，95%置信区间（CI）= 0.89 - 18.01，P = 0.071）和开始吸烟年龄（每年增加的OR = 0.96，95% CI = 0.91 - 1.01，P = 0.098）与精神分裂症无显著关联；效应方向与欧洲血统样本一致，后者具有更高的统计效力。这些发现提供了初步证据，支持吸烟在东亚人群精神分裂症发展中起因果作用。
