Mendelian randomisation study of body composition and depression in people of East Asian ancestry highlights potential setting-specific causality.
BMI
Depression
East Asian ancestry
Mendelian randomisation
Public health
Setting-specific causality
Sociocultural factors
Journal
BMC medicine
ISSN: 1741-7015
Titre abrégé: BMC Med
Pays: England
ID NLM: 101190723
Informations de publication
Date de publication:
01 02 2023
01 02 2023
Historique:
received:
18
05
2022
accepted:
12
01
2023
entrez:
2
2
2023
pubmed:
3
2
2023
medline:
4
2
2023
Statut:
epublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 36726144
doi: 10.1186/s12916-023-02735-8
pii: 10.1186/s12916-023-02735-8
pmc: PMC9893684
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
37Subventions
Organisme : Cancer Research UK
ID : C16077/A29186
Pays : United Kingdom
Organisme : Wellcome Trust
ID : WT220390
Pays : United Kingdom
Organisme : UK Medical Research Council
ID : MR/M020894/1
Organisme : Wellcome Trust
ID : 088158/Z/09/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 104085/Z/14/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC-PC-14135
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U137686851
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00011/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00017/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 212946/Z/18/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC-PC-13049
Pays : United Kingdom
Organisme : British Heart Foundation
ID : CH/1996001/9454
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 202922/Z/16/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12026/2
Pays : United Kingdom
Organisme : Wellcome Trust
ID : WT104150
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C500/A16896
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_14135
Pays : United Kingdom
Informations de copyright
© 2023. The Author(s).
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