A Phenome-Wide Association and Mendelian Randomization Study of Genetically Predicted Membranous Nephropathy with Multiple Diseases.

IF 2.1 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Kidney & blood pressure research Pub Date : 2026-01-01 Epub Date: 2026-02-26 DOI:10.1159/000551046

Alida Wenghaerbai, Akehu Alemasi, Lijiang Gu, Jianjun Deng, Yilun Zhou

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Abstract

Introduction: Membranous nephropathy constitutes a significant proportion of cases leading to end-stage renal disease. In such instances, the accurate distinction between primary and secondary forms is crucial for proper treatment. Consequently, we systematically examined the link between genetically predicted membranous nephropathy and various diseases.

Methods: The phenome-wide association approach assessed the links between genetically predicted membranous nephropathy and 2,408 diseases. Two-sample Mendelian randomization was then employed to explore causal relationships using methods like inverse variance weighting, MR-Egger, weighted median, and others. A replication analysis was conducted to confirm these associations. Gene enrichment analysis was conducted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses to explore potential pathogenic mechanisms.

Results: A statistically significant association was noted between genetically predicted Graves' disease, thyrotoxicosis, and thyrotoxicosis with diffuse goiter and an elevated risk of membranous nephropathy. Subsequent replication analysis for Graves' disease demonstrated consistent results. Functional analysis suggests that Graves' disease may affect membranous nephropathy by influencing pathophysiological mechanisms and pathways related to the proliferation and differentiation of lymphocytes and leukocytes, adhesion between leukocytes and cells, differentiation of CD4+ αβ T cells, and differentiation of Th1 and Th2 cells.

Conclusion: Our study indicates that genetically predicted thyrotoxicosis, thyrotoxicosis with diffuse goiter, and Graves' disease are correlated with an increased likelihood of membranous nephropathy. Graves' disease may affect membranous nephropathy development by influencing leukocyte proliferation and differentiation. Additional research is warranted to validate these findings and ascertain their relevance in clinical management.

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遗传预测膜性肾病伴多种疾病的全表型关联和孟德尔随机化研究。

背景：膜性肾病在导致终末期肾脏疾病的病例中占很大比例。在这种情况下，准确区分初级和次级形式对于适当治疗至关重要。因此，我们系统地检查了遗传预测膜性肾病和各种疾病之间的联系。方法：全现象关联方法评估遗传预测膜性肾病与2408种疾病之间的联系。然后采用双样本孟德尔随机化来探索因果关系，使用反方差加权、MR-Egger、加权中位数等方法。进行了重复分析以证实这些关联。利用基因本体（Gene Ontology）和京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes）进行基因富集分析，探索潜在的致病机制。结果：遗传预测的Graves病、甲状腺毒症和甲状腺毒症伴弥漫性甲状腺肿与膜性肾病风险升高之间存在统计学意义上的相关性。随后对Graves病的重复分析显示了一致的结果。功能分析提示Graves病可能通过影响淋巴细胞和白细胞的增殖分化、白细胞与细胞间的粘附、CD4+ αβ T细胞的分化、Th1和Th2细胞的分化等相关病理生理机制和通路影响膜性肾病。结论：我们的研究表明，基因预测甲状腺毒症、甲状腺毒症伴弥漫性甲状腺肿和Graves病与膜性肾病的可能性增加相关。Graves病可能通过影响白细胞增殖和分化影响膜性肾病的发展。需要进一步的研究来验证这些发现，并确定其与临床管理的相关性。

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来源期刊

Kidney & blood pressure research 医学-泌尿学与肾脏学

CiteScore

4.80

自引率

3.60%

发文量

审稿时长

6-12 weeks

期刊介绍： This journal comprises both clinical and basic studies at the interface of nephrology, hypertension and cardiovascular research. The topics to be covered include the structural organization and biochemistry of the normal and diseased kidney, the molecular biology of transporters, the physiology and pathophysiology of glomerular filtration and tubular transport, endothelial and vascular smooth muscle cell function and blood pressure control, as well as water, electrolyte and mineral metabolism. Also discussed are the (patho)physiology and (patho) biochemistry of renal hormones, the molecular biology, genetics and clinical course of renal disease and hypertension, the renal elimination, action and clinical use of drugs, as well as dialysis and transplantation. Featuring peer-reviewed original papers, editorials translating basic science into patient-oriented research and disease, in depth reviews, and regular special topic sections, ''Kidney & Blood Pressure Research'' is an important source of information for researchers in nephrology and cardiovascular medicine.