Mendelian randomisation study of body composition and depression in people of East Asian ancestry highlights potential setting-specific causality
Abstract Background Extensive evidence links higher body mass index (BMI) to higher odds of depression in people of European ancestry. However, our understanding of the relationship across different settings and ancestries is limited. Here, we test the relationship between body composition and depre...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-02-01
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| Series: | BMC Medicine |
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| Online Access: | https://doi.org/10.1186/s12916-023-02735-8 |
| _version_ | 1811171718099632128 |
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| author | Jessica O’Loughlin Francesco Casanova Zammy Fairhurst-Hunter Amanda Hughes Jack Bowden Edward R. Watkins Rachel M. Freathy Iona Y. Millwood Kuang Lin Zhengming Chen Liming Li Jun Lv China Kadoorie Biobank Collaborative Group Robin G. Walters Laura D. Howe Karoline Kuchenbaecker Jessica Tyrrell |
| author_facet | Jessica O’Loughlin Francesco Casanova Zammy Fairhurst-Hunter Amanda Hughes Jack Bowden Edward R. Watkins Rachel M. Freathy Iona Y. Millwood Kuang Lin Zhengming Chen Liming Li Jun Lv China Kadoorie Biobank Collaborative Group Robin G. Walters Laura D. Howe Karoline Kuchenbaecker Jessica Tyrrell |
| author_sort | Jessica O’Loughlin |
| collection | DOAJ |
| description | Abstract Background Extensive evidence links higher body mass index (BMI) to higher odds of depression in people of European ancestry. However, our understanding of the relationship across different settings and ancestries is limited. Here, we test the relationship between body composition and depression in people of East Asian ancestry. Methods Multiple Mendelian randomisation (MR) methods were used to test the relationship between (a) BMI and (b) waist-hip ratio (WHR) with depression. Firstly, we performed two-sample MR using genetic summary statistics from a recent genome-wide association study (GWAS) of depression (with 15,771 cases and 178,777 controls) in people of East Asian ancestry. We selected 838 single nucleotide polymorphisms (SNPs) correlated with BMI and 263 SNPs correlated with WHR as genetic instrumental variables to estimate the causal effect of BMI and WHR on depression using the inverse-variance weighted (IVW) method. We repeated these analyses stratifying by home location status: China versus UK or USA. Secondly, we performed one-sample MR in the China Kadoorie Biobank (CKB) in 100,377 participants. This allowed us to test the relationship separately in (a) males and females and (b) urban and rural dwellers. We also examined (c) the linearity of the BMI-depression relationship. Results Both MR analyses provided evidence that higher BMI was associated with lower odds of depression. For example, a genetically-instrumented 1-SD higher BMI in the CKB was associated with lower odds of depressive symptoms [OR: 0.77, 95% CI: 0.63, 0.95]. There was evidence of differences according to place of residence. Using the IVW method, higher BMI was associated with lower odds of depression in people of East Asian ancestry living in China but there was no evidence for an association in people of East Asian ancestry living in the USA or UK. Furthermore, higher genetic BMI was associated with differential effects in urban and rural dwellers within China. Conclusions This study provides the first MR evidence for an inverse relationship between BMI and depression in people of East Asian ancestry. This contrasts with previous findings in European populations and therefore the public health response to obesity and depression is likely to need to differ based on sociocultural factors for example, ancestry and place of residence. This highlights the importance of setting-specific causality when using genetic causal inference approaches and data from diverse populations to test hypotheses. This is especially important when the relationship tested is not purely biological and may involve sociocultural factors. |
| first_indexed | 2024-04-10T17:18:40Z |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-04-10T17:18:40Z |
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| spelling | doaj.art-b988fbc958514c1c912a14881ef3828e2023-02-05T12:15:13ZengBMCBMC Medicine1741-70152023-02-0121111410.1186/s12916-023-02735-8Mendelian randomisation study of body composition and depression in people of East Asian ancestry highlights potential setting-specific causalityJessica O’Loughlin0Francesco Casanova1Zammy Fairhurst-Hunter2Amanda Hughes3Jack Bowden4Edward R. Watkins5Rachel M. Freathy6Iona Y. Millwood7Kuang Lin8Zhengming Chen9Liming Li10Jun Lv11China Kadoorie Biobank Collaborative GroupRobin G. Walters12Laura D. Howe13Karoline Kuchenbaecker14Jessica Tyrrell15Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of ExeterDepartment of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of ExeterClinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of OxfordMRC Integrative Epidemiology Unit (IEU), Bristol Medical School, Population Health Sciences, University of BristolDepartment of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of ExeterDepartment of Psychology, University of ExeterDepartment of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of ExeterClinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of OxfordClinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of OxfordClinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of OxfordDepartment of Epidemiology and Biostatistics, School of Public Health, Peking UniversityDepartment of Epidemiology and Biostatistics, School of Public Health, Peking UniversityClinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of OxfordMRC Integrative Epidemiology Unit (IEU), Bristol Medical School, Population Health Sciences, University of BristolDivision of Psychiatry, UCL Genetics Institute, University College LondonDepartment of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of ExeterAbstract Background Extensive evidence links higher body mass index (BMI) to higher odds of depression in people of European ancestry. However, our understanding of the relationship across different settings and ancestries is limited. Here, we test the relationship between body composition and depression in people of East Asian ancestry. Methods Multiple Mendelian randomisation (MR) methods were used to test the relationship between (a) BMI and (b) waist-hip ratio (WHR) with depression. Firstly, we performed two-sample MR using genetic summary statistics from a recent genome-wide association study (GWAS) of depression (with 15,771 cases and 178,777 controls) in people of East Asian ancestry. We selected 838 single nucleotide polymorphisms (SNPs) correlated with BMI and 263 SNPs correlated with WHR as genetic instrumental variables to estimate the causal effect of BMI and WHR on depression using the inverse-variance weighted (IVW) method. We repeated these analyses stratifying by home location status: China versus UK or USA. Secondly, we performed one-sample MR in the China Kadoorie Biobank (CKB) in 100,377 participants. This allowed us to test the relationship separately in (a) males and females and (b) urban and rural dwellers. We also examined (c) the linearity of the BMI-depression relationship. Results Both MR analyses provided evidence that higher BMI was associated with lower odds of depression. For example, a genetically-instrumented 1-SD higher BMI in the CKB was associated with lower odds of depressive symptoms [OR: 0.77, 95% CI: 0.63, 0.95]. There was evidence of differences according to place of residence. Using the IVW method, higher BMI was associated with lower odds of depression in people of East Asian ancestry living in China but there was no evidence for an association in people of East Asian ancestry living in the USA or UK. Furthermore, higher genetic BMI was associated with differential effects in urban and rural dwellers within China. Conclusions This study provides the first MR evidence for an inverse relationship between BMI and depression in people of East Asian ancestry. This contrasts with previous findings in European populations and therefore the public health response to obesity and depression is likely to need to differ based on sociocultural factors for example, ancestry and place of residence. This highlights the importance of setting-specific causality when using genetic causal inference approaches and data from diverse populations to test hypotheses. This is especially important when the relationship tested is not purely biological and may involve sociocultural factors.https://doi.org/10.1186/s12916-023-02735-8Mendelian randomisationBMIDepressionEast Asian ancestryPublic healthSetting-specific causality |
| spellingShingle | Jessica O’Loughlin Francesco Casanova Zammy Fairhurst-Hunter Amanda Hughes Jack Bowden Edward R. Watkins Rachel M. Freathy Iona Y. Millwood Kuang Lin Zhengming Chen Liming Li Jun Lv China Kadoorie Biobank Collaborative Group Robin G. Walters Laura D. Howe Karoline Kuchenbaecker Jessica Tyrrell Mendelian randomisation study of body composition and depression in people of East Asian ancestry highlights potential setting-specific causality BMC Medicine Mendelian randomisation BMI Depression East Asian ancestry Public health Setting-specific causality |
| title | Mendelian randomisation study of body composition and depression in people of East Asian ancestry highlights potential setting-specific causality |
| title_full | Mendelian randomisation study of body composition and depression in people of East Asian ancestry highlights potential setting-specific causality |
| title_fullStr | Mendelian randomisation study of body composition and depression in people of East Asian ancestry highlights potential setting-specific causality |
| title_full_unstemmed | Mendelian randomisation study of body composition and depression in people of East Asian ancestry highlights potential setting-specific causality |
| title_short | Mendelian randomisation study of body composition and depression in people of East Asian ancestry highlights potential setting-specific causality |
| title_sort | mendelian randomisation study of body composition and depression in people of east asian ancestry highlights potential setting specific causality |
| topic | Mendelian randomisation BMI Depression East Asian ancestry Public health Setting-specific causality |
| url | https://doi.org/10.1186/s12916-023-02735-8 |
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