Two⁃sample Mendelian randomization analysis of the causal relationship between obesity⁃related factors and immunoglobulin A nephropathy

SUN Shuaigang; ZHAI Yaling; SHENG Xiaoxiao; ZHANG Wenhui; TIAN Huijuan; LI Meihan; LI Qianqian

doi:10.14188/j.1671-8852.2024.0655

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Two⁃sample Mendelian randomization analysis of the causal relationship between obesity⁃related factors and immunoglobulin A nephropathy

更新时间：2026-11-05

- Two⁃sample Mendelian randomization analysis of the causal relationship between obesity⁃related factors and immunoglobulin A nephropathy
- Medical Journal of Wuhan University Vol. 46, Issue 10, Pages: 1293-1300(2025)
- 作者机构：
  
  郑州大学第一附属医院肾脏内科/郑州大学肾脏病研究所河南郑州 450000
- 作者简介：
- 基金信息：
- DOI：10.14188/j.1671-8852.2024.0655
  CLC： R692.6
- Received：29 August 2024，
  
  Published：25 October 2025
- 稿件说明：
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孙帅刚,翟亚玲,盛晓笑等.双样本孟德尔随机化分析肥胖相关指标与免疫球蛋白A肾病的因果关联[J].武汉大学学报（医学版）,2025,46(10):1293-1300.

SUN Shuaigang,ZHAI Yaling,SHENG Xiaoxiao,et al.Two⁃sample Mendelian randomization analysis of the causal relationship between obesity⁃related factors and immunoglobulin A nephropathy[J].Medical Journal of Wuhan University,2025,46(10):1293-1300.
孙帅刚,翟亚玲,盛晓笑等.双样本孟德尔随机化分析肥胖相关指标与免疫球蛋白A肾病的因果关联[J].武汉大学学报（医学版）,2025,46(10):1293-1300. DOI： 10.14188/j.1671-8852.2024.0655.

SUN Shuaigang,ZHAI Yaling,SHENG Xiaoxiao,et al.Two⁃sample Mendelian randomization analysis of the causal relationship between obesity⁃related factors and immunoglobulin A nephropathy[J].Medical Journal of Wuhan University,2025,46(10):1293-1300. DOI： 10.14188/j.1671-8852.2024.0655.

摘要

目的

基于孟德尔随机化（MR）分析探讨肥胖相关指标与免疫球蛋白A肾病（IgAN）间潜在的因果关联。

方法

提取体质量指数（BMI）、全身脂肪量、体脂率、躯干脂肪量、躯干脂肪率、腰围、臀围、腰臀比和IgAN的大规模全基因组关联研究（GWAS）的汇总数据，以逆方差加权法（IVW）作为主要结果进行双向MR分析。通过Cochran's

检验、MR⁃Egger截距检验、MR⁃PRESS

O检验和留一法证实结果的准确性和稳定性。

结果

基因预测的BMI（

=1.202

95%

:1.121~1.288

=2.009×10

-7

）、全身脂肪量（

=1.215

95%

:1.129~1.307

=1.827×10

-7

）、体脂率（

=1.144

95%

:1.023~1.279

=1.864×10

-2

）、躯干脂肪量（

=1.227

95%

:1.136~1.326

=1.994×10

-7

）、躯干脂肪率（

=1.113

95%

.011~1.227

=0.030）、腰围（

=1.255

95%

:1.148~1.371

=5.712×10

-7

）、臀围（

=1.175

95%

:1.085~1.274

=7.997×10

-5

）与发生IgAN的风险呈正相关，但尚无证据显示腰臀比（

=1.081

95%

:0.855~1.368

=0.516）与IgAN之间存在可靠的因果关系。这些结果在一系列敏感性分析中是可靠的。此外，反向MR分析显示，IgAN可能不会增加肥胖的风险。

结论

肥胖会增加罹患IgAN的风险，预防肥胖可能是降低IgAN风险的重要策略。

Abstract

Objective

To investigate the potential causal association between obesity⁃related factors and immunoglobulin A nephropathy (IgAN) based on Mendelian randomization (MR).

Methods

The summary⁃level data of body mass index (BMI)

whole⁃body fat mass

body fat percentage

trunk fat mass

trunk fat percentage

waist circumference

hip circumference

waist⁃to⁃hip ratio and IgAN from large⁃scale Genome⁃Wide Association Studies (GWAS) of European ancestry were extracted to conduct bidirectional MR analysis using the inverse variance weighted (IVW) method as primary results. The Cochran's

test

MR⁃Egger regression intercept test

MR⁃PRESSO

and leave⁃one⁃out sensitivity analysis were conducted to confirm the accuracy and robustness of results.

Results

The evidence provided by primary MR analysis showed tha

t genetically predicted BMI (

=1.202

95%

: 1.121⁃1.227

=2.009×10

-7

)

whole⁃body fat mass (

=1.215

95%

:1.129⁃1.307

=1.827×10

-7

)

body fat percentage (

=1.144

95%

:1.023⁃1.279

=1.864×10

-2

)

trunk fat mass (

=1.228

95%

: 1.136⁃1.326

=1.994×10

-7

)

trunk fat percentage (

=1.113

95%

: 1.011⁃1.227

=0.030)

waist circumference (

=1.255

95%

: 1.148⁃1.371

=5.712×10

-7

)

hip circumference (

=1.175

95%

: 1.085⁃1.274

=7.997×10

-5

) was positive associated with the risk of developing IgAN

but no evidence revealed a reliable casual association between waist⁃to⁃hip ratio (

=1.081

95%

: 0.855⁃1.368

=0.516) and IgAN. These results were robust to a series of sensitivity analyses. In addition

the reverse MR analysis showed that IgAN might not cause obesity.

Conclusion

Obesity may increase the risk of developing IgAN

and its prevention could be an important strategy to reduce this risk.

关键词

Keywords

references

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