New insights on underlying shared genetic architectures and causality of underweight and depression in East Asian populations

IF 4.9 2区医学 Q1 CLINICAL NEUROLOGY

Journal of affective disorders Pub Date : 2025-03-21 DOI:10.1016/j.jad.2025.03.126

Ming Chen , Zhen Xiao , Yueya Wang , Wanqi Ou , Cailan Hou , Hao-Zhang Huang

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引用次数: 0

Abstract

Background

Extensive evidence links a lower body mass index (BMI) to higher odds of depression in individuals of East Asian ancestry, differing from patterns observed in European populations. However, the shared genetic etiology underlying underweight and depression remains unclear in East Asian populations.

Method

Utilizing large-scale genome-wide association study (GWAS) data, we investigated the shared genetics between BMI (N = 323,298) and depression traits (N = 286,052) through linkage disequilibrium score regression, cross-trait meta-analysis and colocalization analysis. Additionally, we evaluated causal associations using bidirectional Mendelian randomization (MR) analysis.

Results

We found a significantly negative genetic correlation between BMI and depression (rg = −0.19, P = 0.002). The cross-trait analysis identified 26 shared risk SNPs, including FTO and more. Moreover, the risk gene AGBL4 showed evidence of colocalization. Using the MR method, lower BMI was associated with higher odds of depression in individuals of East Asian ancestry (OR: 1.14, 95 % CI: 1.02 to 1.28, P = 0.021) but no reverse causal effect was observed.

Conclusions

Our study indicates a genetic correlation, shared risk genes, and causality between underweight and depression in East Asian populations. These findings provide insights into the potential mechanisms behind their comorbidity and inform the future development of therapeutics for East Asian populations.

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来源期刊

Journal of affective disorders 医学-精神病学

CiteScore

10.90

自引率

6.10%

发文量

1319

审稿时长

9.3 weeks

期刊介绍： The Journal of Affective Disorders publishes papers concerned with affective disorders in the widest sense: depression, mania, mood spectrum, emotions and personality, anxiety and stress. It is interdisciplinary and aims to bring together different approaches for a diverse readership. Top quality papers will be accepted dealing with any aspect of affective disorders, including neuroimaging, cognitive neurosciences, genetics, molecular biology, experimental and clinical neurosciences, pharmacology, neuroimmunoendocrinology, intervention and treatment trials.