Objectives Previous studies have indicated that elevated selenium levels curb systemic lupus erythematosus (SLE) risk, whereas the specific mechanisms remain to be elucidated. Thereby, our study is conducted to explore the mediating function of proteome on the association between selenium and SLE. Methods Summary data for plasma proteins came from six large-scale genome wide association studies (GWASs). The data of selenium were derived from a GWAS meta-analysis involving 9639 individuals, and those with SLE were obtained from SLE meta-GWASs (5206 cases and 9066 controls). Two-sample Mendelian randomization (MR) was performed using inverse-variance weighting (IVW), followed by a series of sensitivity analyses to examine the causal relationship between plasma proteins and SLE. Additionally, a two-step MR (TSMR) analysis was applied to explore the mediating role of plasma proteins in the link between selenium and SLE. Moreover, multivariable MR (MVMR) was utilized to adjust and calculate the mediating effect, revealing the potential mechanisms underlying the impact of selenium on SLE. Results In the MR analysis, we found 24 plasma proteins associated with SLE among 4372 unique plasma proteins. Notably, three plasma proteins exhibited a causal link with selenium. Through mediation analysis, we identified sex hormone–binding globulin (SHBG) mediated the causal effect between selenium and SLE. Specifically, increased selenium levels could lower SLE risk by reducing SHBG levels, with a mediation proportion of 22% (95% CI 13–54%). Conclusions This research highlights the key mediating role of plasma proteins in the association between selenium and SLE, which elucidates the targeted protein as SHBG for the relationship. <Table Float="No" ID="Taba"> <tgroup cols="2"> <colspec align="left" colname="c1" colnum="1" /> <colspec align="left" colname="c2" colnum="2" /> <tbody> <row> <entry align="left" nameend="c2" namest="c1"> Key Points • The research genetically predicted a causal link between plasma proteins and SLE. • The study revealed that plasma proteins mediate the relationship between selenium and SLE. • The findings offer new perspectives and potential intervention targets for SLE prevention through SHBG. </entry> </row> </tbody> </tgroup> </Table>

The mediating effects of plasma proteome on the association between selenium and systemic lupus erythematosus

期刊论文
发表日期：

2026年6月20日

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Zeyue Chen,
Ying Chen,
Jiayu Li,
Xiaohui Sun,
Zhixing He,
Chengping Wen,
Yingying Mao,
Ding Ye

摘要

Objectives

Previous studies have indicated that elevated selenium levels curb systemic lupus erythematosus (SLE) risk, whereas the specific mechanisms remain to be elucidated. Thereby, our study is conducted to explore the mediating function of proteome on the association between selenium and SLE.

Methods

Summary data for plasma proteins came from six large-scale genome wide association studies (GWASs). The data of selenium were derived from a GWAS meta-analysis involving 9639 individuals, and those with SLE were obtained from SLE meta-GWASs (5206 cases and 9066 controls). Two-sample Mendelian randomization (MR) was performed using inverse-variance weighting (IVW), followed by a series of sensitivity analyses to examine the causal relationship between plasma proteins and SLE. Additionally, a two-step MR (TSMR) analysis was applied to explore the mediating role of plasma proteins in the link between selenium and SLE. Moreover, multivariable MR (MVMR) was utilized to adjust and calculate the mediating effect, revealing the potential mechanisms underlying the impact of selenium on SLE.

Results

In the MR analysis, we found 24 plasma proteins associated with SLE among 4372 unique plasma proteins. Notably, three plasma proteins exhibited a causal link with selenium. Through mediation analysis, we identified sex hormone–binding globulin (SHBG) mediated the causal effect between selenium and SLE. Specifically, increased selenium levels could lower SLE risk by reducing SHBG levels, with a mediation proportion of 22% (95% CI 13–54%).

Conclusions

This research highlights the key mediating role of plasma proteins in the association between selenium and SLE, which elucidates the targeted protein as SHBG for the relationship.

Key Points

• The research genetically predicted a causal link between plasma proteins and SLE.

• The study revealed that plasma proteins mediate the relationship between selenium and SLE.

• The findings offer new perspectives and potential intervention targets for SLE prevention through SHBG.