| Title: |
Mendelian randomisation study of body composition and depression in people of East Asian ancestry highlights potential setting-specific causality |
| Authors: |
O'Loughlin, J; Casanova, F; Fairhurst-Hunter, Z; Hughes, A; Bowden, J; Watkins, ER; Freathy, RM; Millwood, IY; Lin, K; Chen, Z; Li, L; Lv, J; Walters, RG; Howe, LD; Kuchenbaecker, K; Tyrrell, J |
| Contributors: |
Group, China Kadoorie Biobank Collaborative |
| Publisher Information: |
BioMed Central |
| Publication Year: |
2023 |
| Collection: |
Oxford University Research Archive (ORA) |
| Description: |
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 ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1186/s12916-023-02735-8 |
| Availability: |
https://doi.org/10.1186/s12916-023-02735-8; https://ora.ox.ac.uk/objects/uuid:5d9f92b2-0cf3-4692-89ae-4956509770a1 |
| Rights: |
info:eu-repo/semantics/openAccess ; CC Attribution (CC BY) |
| Accession Number: |
edsbas.8E2BC766 |
| Database: |
BASE |