Investigating the possible causal association of smoking with depression and anxiety using Mendelian randomisation meta-analysis: the CARTA consortium.

BMJ Open
Authors
Keywords
Abstract

OBJECTIVES: To investigate whether associations of smoking with depression and anxiety are likely to be causal, using a Mendelian randomisation approach.

DESIGN: Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730) as a proxy for smoking heaviness, and observational meta-analyses of the associations of smoking status and smoking heaviness with depression, anxiety and psychological distress.

PARTICIPANTS: Current, former and never smokers of European ancestry aged ≥16 years from 25 studies in the Consortium for Causal Analysis Research in Tobacco and Alcohol (CARTA).

PRIMARY OUTCOME MEASURES: Binary definitions of depression, anxiety and psychological distress assessed by clinical interview, symptom scales or self-reported recall of clinician diagnosis.

RESULTS: The analytic sample included up to 58 176 never smokers, 37 428 former smokers and 32 028 current smokers (total N=127 632). In observational analyses, current smokers had 1.85 times greater odds of depression (95% CI 1.65 to 2.07), 1.71 times greater odds of anxiety (95% CI 1.54 to 1.90) and 1.69 times greater odds of psychological distress (95% CI 1.56 to 1.83) than never smokers. Former smokers also had greater odds of depression, anxiety and psychological distress than never smokers. There was evidence for positive associations of smoking heaviness with depression, anxiety and psychological distress (ORs per cigarette per day: 1.03 (95% CI 1.02 to 1.04), 1.03 (95% CI 1.02 to 1.04) and 1.02 (95% CI 1.02 to 1.03) respectively). In Mendelian randomisation analyses, there was no strong evidence that the minor allele of rs16969968/rs1051730 was associated with depression (OR=1.00, 95% CI 0.95 to 1.05), anxiety (OR=1.02, 95% CI 0.97 to 1.07) or psychological distress (OR=1.02, 95% CI 0.98 to 1.06) in current smokers. Results were similar for former smokers.

CONCLUSIONS: Findings from Mendelian randomisation analyses do not support a causal role of smoking heaviness in the development of depression and anxiety.

Year of Publication
2014
Journal
BMJ Open
Volume
4
Issue
10
Pages
e006141
Date Published
2014 Oct 07
ISSN
2044-6055
URL
DOI
10.1136/bmjopen-2014-006141
PubMed ID
25293386
PubMed Central ID
PMC4187451
Links
Grant list
G0100266 / Medical Research Council / United Kingdom
PG/09/022/26739 / British Heart Foundation / United Kingdom
R01 MH063706 / MH / NIMH NIH HHS / United States
092731 / Wellcome Trust / United Kingdom
PG/13/66/30442 / British Heart Foundation / United Kingdom
R01 HL036310 / HL / NHLBI NIH HHS / United States
0090049 / Department of Health / United Kingdom
MH077874 / MH / NIMH NIH HHS / United States
R01 HL087679 / HL / NHLBI NIH HHS / United States
R01 DA024413 / DA / NIDA NIH HHS / United States
MC_UU_12013/6 / Medical Research Council / United Kingdom
G0802736 / Medical Research Council / United Kingdom
AG13196 / AG / NIA NIH HHS / United States
R01 MH077874 / MH / NIMH NIH HHS / United States
MC_UU_12019/1 / Medical Research Council / United Kingdom
MR/K023195/1 / Medical Research Council / United Kingdom
MR/J012165/1 / Medical Research Council / United Kingdom
1RL1MH083268-01 / MH / NIMH NIH HHS / United States
MC_UU_12013/1 / Medical Research Council / United Kingdom
MR/K026992/1 / Medical Research Council / United Kingdom
G0500539 / Medical Research Council / United Kingdom
102215 / Wellcome Trust / United Kingdom
076113 / Wellcome Trust / United Kingdom
R37 AG013196 / AG / NIA NIH HHS / United States
MR/K023233/1 / Medical Research Council / United Kingdom
U01 DK062418 / DK / NIDDK NIH HHS / United States
284167 / European Research Council / International
MC_PC_15018 / Medical Research Council / United Kingdom
HL36310 / HL / NHLBI NIH HHS / United States
PG/07/131/24254 / British Heart Foundation / United Kingdom
R01DA024413 / DA / NIDA NIH HHS / United States
CZD/16/6/4 / Chief Scientist Office / United Kingdom
MC_PC_U127561128 / Medical Research Council / United Kingdom
R01AG1764406S1 / AG / NIA NIH HHS / United States
UL1 TR001425 / TR / NCATS NIH HHS / United States
R01 AG017644 / AG / NIA NIH HHS / United States
R01 AG013196 / AG / NIA NIH HHS / United States
R01 DA018673 / DA / NIDA NIH HHS / United States
068545/Z/02 / Wellcome Trust / United Kingdom
HS06516 / HS / AHRQ HHS / United States
RL1 MH083268 / MH / NIMH NIH HHS / United States
G1002319 / Medical Research Council / United Kingdom
G0000934 / Medical Research Council / United Kingdom
G0800612 / Medical Research Council / United Kingdom
G0600705 / Medical Research Council / United Kingdom
086684 / Wellcome Trust / United Kingdom
MR/J01351X/1 / Medical Research Council / United Kingdom