Evaluation of the causal relationship between smoking and schizophrenia in East Asia

Mei-Hsin Su; Rou-Yi Lai; Yen-Feng Lin; Chia-Yen Chen; Yen-Chen A Feng; Po-Chang Hsiao; Shi-Heng Wang

doi:10.1038/s41537-022-00281-5

Evaluation of the causal relationship between smoking and schizophrenia in East Asia

Schizophrenia (Heidelb). 2022 Sep 9;8(1):72. doi: 10.1038/s41537-022-00281-5.

Authors

Mei-Hsin Su^{1

2}, Rou-Yi Lai², Yen-Feng Lin³, Chia-Yen Chen^{4

5}, Yen-Chen A Feng⁶, Po-Chang Hsiao⁶, Shi-Heng Wang^{7

8}

Affiliations

¹ Department of Occupational Safety and Health, College of Public Health, China Medical University, Taichung, Taiwan.
² Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan.
³ Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan.
⁴ Biogen, Cambridge, MA, USA.
⁵ Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁶ Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
⁷ Department of Occupational Safety and Health, College of Public Health, China Medical University, Taichung, Taiwan. wangsh@mail.cmu.edu.tw.
⁸ Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan. wangsh@mail.cmu.edu.tw.

Abstract

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.

Abstract

Grants and funding