Investigating the possible causal association of smoking with depression and anxiety using Mendelian randomisation meta-analysis: the CARTA consortium
Authors: Taylor Amy E , Fluharty Meg E , Bjørngaard Johan H , Gabrielsen Maiken Elvestad , Skorpen Frank , Marioni Riccardo E , Campbell Archie , Engmann Jorgen , Mirza Saira Saeed , Loukola Anu , Laatikainen Tiina , Partonen Timo , Kaakinen Marika , Ducci Francesca , Cavadino Alana , Husemoen Lise Lotte N , Ahluwalia Tarunveer Singh , Jacobsen Rikke Kart , Skaaby Tea , Ebstrup Jeanette Frost , Mortensen Erik Lykke , Minica Camelia C , Vink Jacqueline M , Willemsen Gonneke , Marques-Vidal Pedro , Dale Caroline E , Amuzu Antoinette , Lennon Lucy T , Lahti Jari , Palotie Aarno , Räikkönen Katri , Wong Andrew , Paternoster Lavinia , Wong Angelita Pui-Yee , Horwood L John , Murphy Michael , Johnstone Elaine C , Kennedy Martin A , Pausova Zdenka , Paus Tomáš , Ben-Shlomo Yoav , Nohr Ellen A , Kuh Diana , Kivimaki Mika , Eriksson Johan G , Morris Richard W , Casas Juan P , Preisig Martin , Boomsma Dorret I , Linneberg Allan , Power Chris , Hyppönen Elina , Veijola Juha , Jarvelin Marjo-Riitta , Korhonen Tellervo , Tiemeier Henning , Kumari Meena , Porteous David J , Hayward Caroline , Romundstad Pål R , Smith George Davey , Munafò Marcus R 
Published: October 2014

ObjectivesTo investigate whether associations of smoking with depression and anxiety are likely to be causal, using a Mendelian randomisation approach.DesignMendelian 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.ParticipantsCurrent, 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 measuresBinary definitions of depression, anxiety and psychological distress assessed by clinical interview, symptom scales or self-reported recall of clinician diagnosis.ResultsThe 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.ConclusionsFindings from Mendelian randomisation analyses do not support a causal role of smoking heaviness in the development of depression and anxiety.