Dissecting Causal Associations of Diet-Derived Circulating Antioxidants with Six Major Mental Disorders: A Mendelian Randomization Study
Although observational studies have suggested associations between circulating antioxidants and many mental disorders, causal inferences have not been confirmed. Mendelian randomization (MR) analyses were conducted using summary-level statistics from genome-wide association studies (GWASs) to explor...
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MDPI AG
2023-01-01
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author | Hao Zhao Xue Han Xuening Zhang Lingjiang Li Yanzhi Li Wanxin Wang Roger S. McIntyre Kayla M. Teopiz Lan Guo Ciyong Lu |
author_facet | Hao Zhao Xue Han Xuening Zhang Lingjiang Li Yanzhi Li Wanxin Wang Roger S. McIntyre Kayla M. Teopiz Lan Guo Ciyong Lu |
author_sort | Hao Zhao |
collection | DOAJ |
description | Although observational studies have suggested associations between circulating antioxidants and many mental disorders, causal inferences have not been confirmed. Mendelian randomization (MR) analyses were conducted using summary-level statistics from genome-wide association studies (GWASs) to explore whether genetically determined absolute circulating antioxidants (i.e., ascorbate, retinol, β-carotene, and lycopene) and metabolites (i.e., α- and γ-tocopherol, ascorbate, and retinol) were causally associated with the risk of six major mental disorders, including anxiety disorders (AD), major depressive disorder (MDD), bipolar disorder (BIP), schizophrenia (SCZ), post-traumatic stress disorder (PTSD), and obsessive–compulsive disorder (OCD). MR analyses were performed per specific-outcome databases, including the largest GWAS published to date (from 9725 for OCD to 413,466 for BIP participants), UK Biobank (over 370,000 participants), and FinnGen (over 270,000 participants), followed by meta-analyses. We found no significant evidence that genetically determined diet-derived circulating antioxidants were significantly causally associated with the risk of the six above-mentioned major mental disorders. For absolute antioxidant levels, the odds ratios (ORs) ranged from 0.91 (95% CI, 0.67–1.23) for the effect of β-carotene on OCD to 1.18 (95% CI, 0.90–1.54) for the effect of ascorbate on OCD. Similarly, for antioxidant metabolites, ORs ranged from 0.87 (95% CI, 0.55–1.38) for the effect of ascorbate on MDD to 1.08 (95% CI, 0.88–1.33) for the effect of ascorbate on OCD. Our study does not support significant causal associations of genetically determined diet-derived circulating antioxidants with the risk of major mental disorders. |
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language | English |
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series | Antioxidants |
spelling | doaj.art-768ec4138db2409d876b69e2d4f24c872023-11-30T20:59:12ZengMDPI AGAntioxidants2076-39212023-01-0112116210.3390/antiox12010162Dissecting Causal Associations of Diet-Derived Circulating Antioxidants with Six Major Mental Disorders: A Mendelian Randomization StudyHao Zhao0Xue Han1Xuening Zhang2Lingjiang Li3Yanzhi Li4Wanxin Wang5Roger S. McIntyre6Kayla M. Teopiz7Lan Guo8Ciyong Lu9Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Psychiatry, Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen 518054, ChinaDepartment of Epidemiology and Biostatistics, College of Public Health, Shandong University, Jinan 250012, ChinaMental Health Institute of the Second Xiangya Hospital, Central South University, Changsha 410011, ChinaDepartment of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Psychiatry, University of Toronto, Toronto, ON M5T 1R8, CanadaMood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON M5T 2S8, CanadaDepartment of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, ChinaAlthough observational studies have suggested associations between circulating antioxidants and many mental disorders, causal inferences have not been confirmed. Mendelian randomization (MR) analyses were conducted using summary-level statistics from genome-wide association studies (GWASs) to explore whether genetically determined absolute circulating antioxidants (i.e., ascorbate, retinol, β-carotene, and lycopene) and metabolites (i.e., α- and γ-tocopherol, ascorbate, and retinol) were causally associated with the risk of six major mental disorders, including anxiety disorders (AD), major depressive disorder (MDD), bipolar disorder (BIP), schizophrenia (SCZ), post-traumatic stress disorder (PTSD), and obsessive–compulsive disorder (OCD). MR analyses were performed per specific-outcome databases, including the largest GWAS published to date (from 9725 for OCD to 413,466 for BIP participants), UK Biobank (over 370,000 participants), and FinnGen (over 270,000 participants), followed by meta-analyses. We found no significant evidence that genetically determined diet-derived circulating antioxidants were significantly causally associated with the risk of the six above-mentioned major mental disorders. For absolute antioxidant levels, the odds ratios (ORs) ranged from 0.91 (95% CI, 0.67–1.23) for the effect of β-carotene on OCD to 1.18 (95% CI, 0.90–1.54) for the effect of ascorbate on OCD. Similarly, for antioxidant metabolites, ORs ranged from 0.87 (95% CI, 0.55–1.38) for the effect of ascorbate on MDD to 1.08 (95% CI, 0.88–1.33) for the effect of ascorbate on OCD. Our study does not support significant causal associations of genetically determined diet-derived circulating antioxidants with the risk of major mental disorders.https://www.mdpi.com/2076-3921/12/1/162antioxidantmental disordersMendelian randomizationgenome-wide association studiesoxidative stress |
spellingShingle | Hao Zhao Xue Han Xuening Zhang Lingjiang Li Yanzhi Li Wanxin Wang Roger S. McIntyre Kayla M. Teopiz Lan Guo Ciyong Lu Dissecting Causal Associations of Diet-Derived Circulating Antioxidants with Six Major Mental Disorders: A Mendelian Randomization Study Antioxidants antioxidant mental disorders Mendelian randomization genome-wide association studies oxidative stress |
title | Dissecting Causal Associations of Diet-Derived Circulating Antioxidants with Six Major Mental Disorders: A Mendelian Randomization Study |
title_full | Dissecting Causal Associations of Diet-Derived Circulating Antioxidants with Six Major Mental Disorders: A Mendelian Randomization Study |
title_fullStr | Dissecting Causal Associations of Diet-Derived Circulating Antioxidants with Six Major Mental Disorders: A Mendelian Randomization Study |
title_full_unstemmed | Dissecting Causal Associations of Diet-Derived Circulating Antioxidants with Six Major Mental Disorders: A Mendelian Randomization Study |
title_short | Dissecting Causal Associations of Diet-Derived Circulating Antioxidants with Six Major Mental Disorders: A Mendelian Randomization Study |
title_sort | dissecting causal associations of diet derived circulating antioxidants with six major mental disorders a mendelian randomization study |
topic | antioxidant mental disorders Mendelian randomization genome-wide association studies oxidative stress |
url | https://www.mdpi.com/2076-3921/12/1/162 |
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