AUTHOR=Xiong Yang , Zhang Yangchang , Zhang Fuxun , Wu Changjing , Luo Peiyi , Qin Feng , Yuan Jiuhong TITLE=Genetic Evidence Supporting the Causal Role of Homocysteine in Chronic Kidney Disease: A Mendelian Randomization Study JOURNAL=Frontiers in Nutrition VOLUME=9 YEAR=2022 URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2022.843534 DOI=10.3389/fnut.2022.843534 ISSN=2296-861X ABSTRACT=Background

The causal relationship between homocysteine (Hcy) levels and chronic kidney disease (CKD) remains unclear. This study was performed to estimate the potential causal effects of Hcy on the estimated glomerular filtration rate (eGFR) and CKD.

Materials and Methods

The single nucleotide polymorphisms (SNPs) associated with one standard deviation (SD) Hcy increase were identified using the genome-wide association study (GWAS). The summary statistics of the eGFR and CKD were from the CKDGen project in the European ancestry and the Population Architecture using Genomics and Epidemiology (PAGE) project in the non-European ancestry. Two-sample Mendelian randomization (MR) analyses were used in this study to verify the causal effects among Hcy, eGFR, and CKD.

Results

The results showed that 1-SD Hcy increase was causally associated with eGFR decline in the CKDGen project (β = −0.027 log ml.min–1/1.73 m2, p < 0.01 for the overall cohort; β = −0.028 log ml.min–1/1.73 m2, p < 0.01 after excluding the patients with diabetes). In addition, 1-SD Hcy increase was associated with a 1.32-fold risk of CKD in the PAGE project (95% CI = 1.06–1.64, p < 0.05). The association was directionally similar in the CKDGen project [odds ratio (OR) = 1.08, 95% CI = 0.97–1.44, p = 0.098]. The pooled OR of CKD was 1.24 (95% CI = 1.07–1.44, p < 0.05) per 1-SD Hcy increase.

Conclusion

Using genetic data, Hcy increase is causally associated with renal function injury and further CKD.