Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Investigating causality in associations between smoking initiation and schizophrenia using Mendelian randomization

Gage, Suzanne H., Jones, Hannah J., Taylor, Amy E., Burgess, Stephen, Zammit, Stanley ORCID: https://orcid.org/0000-0002-2647-9211 and Munafò, Marcus R. 2017. Investigating causality in associations between smoking initiation and schizophrenia using Mendelian randomization. Scientific Reports 7 , 40653. 10.1038/srep40653

[thumbnail of Gage_et_al-2017-Scientific_Reports.pdf]
Preview
PDF - Published Version
Available under License Creative Commons Attribution.

Download (553kB) | Preview

Abstract

Smoking is strongly associated with schizophrenia. Although it has been widely assumed that this reflects self-medication, recent studies suggest that smoking may be a risk factor for schizophrenia. We performed two-sample bi-directional Mendelian randomization using summary level genomewide association data from the Tobacco And Genetics Consortium and Psychiatric Genomics Consortium. Variants associated with smoking initiation and schizophrenia were combined using an inverse-variance weighted fixed-effects approach. We found evidence consistent with a causal effect of smoking initiation on schizophrenia risk (OR 1.73, 95% CI 1.30–2.25, p < 0.001). However, after relaxing the p-value threshold to include variants from more than one gene and minimize the potential impact of pleiotropy, the association was attenuated (OR 1.03, 95% CI 0.97–1.09, p = 0.32). There was little evidence in support of a causal effect of schizophrenia on smoking initiation (OR 1.01, 95% CI 0.98–1.04, p = 0.32). MR Egger regression sensitivity analysis indicated no evidence for pleiotropy in the effect of schizophrenia on smoking initiation (intercept OR 1.01, 95% CI 0.99–1.02, p = 0.49). Our findings provide little evidence of a causal association between smoking initiation and schizophrenia, in either direction. However, we cannot rule out a causal effect of smoking on schizophrenia related to heavier, lifetime exposure, rather than initiation.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects: R Medicine > R Medicine (General)
Publisher: Nature Publishing Group
ISSN: 2045-2322
Date of First Compliant Deposit: 16 February 2017
Date of Acceptance: 9 December 2016
Last Modified: 05 May 2023 07:37
URI: https://orca.cardiff.ac.uk/id/eprint/98348

Citation Data

Cited 40 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics