Genetically Predicted Body Selenium Concentration and estimated GFR: A Mendelian Randomization Study

Sehoon Park; Seong Geun Kim; Soojin Lee; Yaerim Kim; Semin Cho; Kwangsoo Kim; Yong Chul Kim; Seung Seok Han; Hajeong Lee; Jung Pyo Lee; Kwon Wook Joo; Chun Soo Lim; Yon Su Kim; Dong Ki Kim

doi:10.1016/j.ekir.2023.01.009

Genetically Predicted Body Selenium Concentration and estimated GFR: A Mendelian Randomization Study

Kidney Int Rep. 2023 Jan 20;8(4):851-859. doi: 10.1016/j.ekir.2023.01.009. eCollection 2023 Apr.

Authors

Sehoon Park^{1

2}, Seong Geun Kim², Soojin Lee^{3

4}, Yaerim Kim⁵, Semin Cho⁶, Kwangsoo Kim⁷, Yong Chul Kim², Seung Seok Han^{2

8}, Hajeong Lee², Jung Pyo Lee^{4

8

9}, Kwon Wook Joo^{2

4

8}, Chun Soo Lim^{4

8

9}, Yon Su Kim^{1

2

4

8}, Dong Ki Kim^{2

4

8}

Affiliations

¹ Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
² Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
³ Department of Internal Medicine, Uijeongbu Eulji University Medical Center, Seoul, Korea.
⁴ Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
⁵ Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea.
⁶ Department of Internal Medicine, Chung-Ang University Gwangmyeong Hospital, Gyeonggi-do, Korea.
⁷ Transdisciplinary Department of Medicine & Advanced Technology, Seoul National University Hospital, Seoul, Korea.
⁸ Kidney Research Institute, Seoul National University, Seoul, Korea.
⁹ Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea.

Abstract

Introduction: Selenium is a trace mineral that is commonly included in micronutrient supplements. The effect of selenium on kidney function remains unclear. A genetically predicted micronutrient and its association with estimated glomerular filtration rate (eGFR) can be used to assess the causal estimates by Mendelian randomization (MR).

Methods: In this MR study, we instrumented 11 genetic variants associated with blood or total selenium levels from a previous genome-wide association study (GWAS). The association between genetically predicted selenium concentration and eGFR was first assessed by summary-level MR in the chronic kidney disease(CKDGen) GWAS meta-analysis summary statistics, including 567,460 European samples. Inverse-variance weighted and pleiotropy-robust MR analyses were performed, in addition to multivariable MR adjusted for the effects of type 2 diabetes mellitus. Replication analysis was performed with individual-level UK Biobank data, including 337,318 White individuals of British ancestry.

Results: Summary-level MR analysis indicated that a genetically predicted 1 SD increase in selenium concentration was significantly associated with lower eGFR (-1.05 [-1.28, -0.82] %). The results were similarly reproduced by pleiotropy-robust MR analysis, including MR-Egger and weighted-median methods, and consistent even in the multivariable MR adjusted for diabetes. In the UK Biobank data, genetically predicted higher selenium concentration was also significantly associated with lower eGFR (- 0.36 [-0.52, -0.20] %), and the results were similar when body mass index, waist circumference, hypertension, and diabetes mellitus covariates were adjusted (-0.33 [-0.50, -0.17] %).

Conclusion: This MR study supports the hypothesis that higher genetically predicted body selenium is causally associated with lower eGFR.

Keywords: Mendelian randomization; genomics; kidney; micronutrient; selenium.