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

Author

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, Tarun Veer 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, 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, Tarun Veer 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, and Munafò, Marcus R

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

Published
2014

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

Author

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

Published
2014
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8. Inter-Regional Variations in Gene Expression and Age-Related Cortical Thinning in the Adolescent Brain.

Author

Wong AP, French L, Leonard G, Perron M, Pike GB, Richer L, Veillette S, Pausova Z, and Paus T

Subjects
Adolescent, Cerebral Cortex diagnostic imaging, Child, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, RNA, Messenger metabolism, Receptors, Androgen genetics, Receptors, Androgen metabolism, Receptors, Estrogen genetics, Receptors, Estrogen metabolism, Receptors, Glucocorticoid genetics, Receptors, Glucocorticoid metabolism, Receptors, Progesterone genetics, Receptors, Progesterone metabolism, Sex Factors, Transcriptome, Aging physiology, Cerebral Cortex physiology, Gene Expression physiology
Abstract

Age-related decreases in cortical thickness observed during adolescence may be related to fluctuations in sex and stress hormones. We examine this possibility by relating inter-regional variations in age-related cortical thinning (data from the Saguenay Youth Study) to inter-regional variations in expression levels of relevant genes (data from the Allen Human Brain Atlas); we focus on genes coding for glucocorticoid receptor (NR3C1), androgen receptor (AR), progesterone receptor (PGR), and estrogen receptors (ESR1 and ESR2). Across 34 cortical regions (Desikan-Killiany parcellation), age-related cortical thinning varied as a function of mRNA expression levels of NR3C1 in males (R2 = 0.46) and females (R2 = 0.30) and AR in males only (R2 = 0.25). Cortical thinning did not vary as a function of expression levels of PGR, ESR1, or ESR2 in either sex; this might be due to the observed low consistency of expression profiles of these 3 genes across donors. Inter-regional levels of the NR3C1 and AR expression interacted with each other vis-à-vis cortical thinning: age-related cortical thinning varied as a function of NR3C1 mRNA expression in brain regions with low (males: R2 = 0.64; females: R2 = 0.58) but not high (males: R2 = 0.0045; females: R2 = 0.15) levels of AR mRNA expression. These results suggest that glucocorticoid and androgen receptors contribute to cortical maturation during adolescence.

Published
2018
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