Cargando…
Causal Effects of Homocysteine, Folate, and Cobalamin on Kidney Function: A Mendelian Randomization Study
Blood homocysteine level and related vitamin levels are associated with various health outcomes. We aimed to assess causal effects of blood homocysteine, folate, and cobalamin on kidney function in the general population by performing Mendelian randomization (MR) analysis. Genetic instruments for bl...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001564/ https://www.ncbi.nlm.nih.gov/pubmed/33799553 http://dx.doi.org/10.3390/nu13030906 |
_version_ | 1783671259715862528 |
---|---|
author | Park, Sehoon Lee, Soojin Kim, Yaerim Cho, Semin Kim, Kwangsoo Kim, Yong Chul Han, Seung Seok Lee, Hajeong Lee, Jung Pyo Joo, Kwon Wook Lim, Chun Soo Kim, Yon Su Kim, Dong Ki |
author_facet | Park, Sehoon Lee, Soojin Kim, Yaerim Cho, Semin Kim, Kwangsoo Kim, Yong Chul Han, Seung Seok Lee, Hajeong Lee, Jung Pyo Joo, Kwon Wook Lim, Chun Soo Kim, Yon Su Kim, Dong Ki |
author_sort | Park, Sehoon |
collection | PubMed |
description | Blood homocysteine level and related vitamin levels are associated with various health outcomes. We aimed to assess causal effects of blood homocysteine, folate, and cobalamin on kidney function in the general population by performing Mendelian randomization (MR) analysis. Genetic instruments for blood homocysteine, folate, and cobalamin levels were introduced from a previous genome-wide association (GWAS) meta-analysis of European individuals. Summary-level MR analysis was performed for the estimated glomerular filtration rate (eGFR) from the CKDGen consortium GWAS that included 567,460 European ancestry individuals. For replication, allele-score-based MR was performed with an independent U.K. Biobank cohort of 337,138 individuals of white British ancestry. In summary-level MR for the CKDGen data, high genetically predicted homocysteine levels were significantly associated with low eGFR (per 1 standard deviation, beta for eGFR change −0.95 (−1.21, −0.69) %), supported by pleiotropy-robust MR sensitivity analysis. Genetically predicted high folate levels were significantly associated with high eGFR change (0.86 (0.30, 1.42) %); however, causal estimates from cobalamin were nonsignificant (−0.11 (−0.33, 0.11) %). In the U.K. Biobank data, the results were consistently identified. Therefore, a high blood homocysteine level causally decreases eGFR. Future trials with appropriate homocysteine-lowering interventions may be helpful for the primary prevention of kidney function impairment. |
format | Online Article Text |
id | pubmed-8001564 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-80015642021-03-28 Causal Effects of Homocysteine, Folate, and Cobalamin on Kidney Function: A Mendelian Randomization Study Park, Sehoon Lee, Soojin Kim, Yaerim Cho, Semin Kim, Kwangsoo Kim, Yong Chul Han, Seung Seok Lee, Hajeong Lee, Jung Pyo Joo, Kwon Wook Lim, Chun Soo Kim, Yon Su Kim, Dong Ki Nutrients Article Blood homocysteine level and related vitamin levels are associated with various health outcomes. We aimed to assess causal effects of blood homocysteine, folate, and cobalamin on kidney function in the general population by performing Mendelian randomization (MR) analysis. Genetic instruments for blood homocysteine, folate, and cobalamin levels were introduced from a previous genome-wide association (GWAS) meta-analysis of European individuals. Summary-level MR analysis was performed for the estimated glomerular filtration rate (eGFR) from the CKDGen consortium GWAS that included 567,460 European ancestry individuals. For replication, allele-score-based MR was performed with an independent U.K. Biobank cohort of 337,138 individuals of white British ancestry. In summary-level MR for the CKDGen data, high genetically predicted homocysteine levels were significantly associated with low eGFR (per 1 standard deviation, beta for eGFR change −0.95 (−1.21, −0.69) %), supported by pleiotropy-robust MR sensitivity analysis. Genetically predicted high folate levels were significantly associated with high eGFR change (0.86 (0.30, 1.42) %); however, causal estimates from cobalamin were nonsignificant (−0.11 (−0.33, 0.11) %). In the U.K. Biobank data, the results were consistently identified. Therefore, a high blood homocysteine level causally decreases eGFR. Future trials with appropriate homocysteine-lowering interventions may be helpful for the primary prevention of kidney function impairment. MDPI 2021-03-11 /pmc/articles/PMC8001564/ /pubmed/33799553 http://dx.doi.org/10.3390/nu13030906 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ). |
spellingShingle | Article Park, Sehoon Lee, Soojin Kim, Yaerim Cho, Semin Kim, Kwangsoo Kim, Yong Chul Han, Seung Seok Lee, Hajeong Lee, Jung Pyo Joo, Kwon Wook Lim, Chun Soo Kim, Yon Su Kim, Dong Ki Causal Effects of Homocysteine, Folate, and Cobalamin on Kidney Function: A Mendelian Randomization Study |
title | Causal Effects of Homocysteine, Folate, and Cobalamin on Kidney Function: A Mendelian Randomization Study |
title_full | Causal Effects of Homocysteine, Folate, and Cobalamin on Kidney Function: A Mendelian Randomization Study |
title_fullStr | Causal Effects of Homocysteine, Folate, and Cobalamin on Kidney Function: A Mendelian Randomization Study |
title_full_unstemmed | Causal Effects of Homocysteine, Folate, and Cobalamin on Kidney Function: A Mendelian Randomization Study |
title_short | Causal Effects of Homocysteine, Folate, and Cobalamin on Kidney Function: A Mendelian Randomization Study |
title_sort | causal effects of homocysteine, folate, and cobalamin on kidney function: a mendelian randomization study |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001564/ https://www.ncbi.nlm.nih.gov/pubmed/33799553 http://dx.doi.org/10.3390/nu13030906 |
work_keys_str_mv | AT parksehoon causaleffectsofhomocysteinefolateandcobalaminonkidneyfunctionamendelianrandomizationstudy AT leesoojin causaleffectsofhomocysteinefolateandcobalaminonkidneyfunctionamendelianrandomizationstudy AT kimyaerim causaleffectsofhomocysteinefolateandcobalaminonkidneyfunctionamendelianrandomizationstudy AT chosemin causaleffectsofhomocysteinefolateandcobalaminonkidneyfunctionamendelianrandomizationstudy AT kimkwangsoo causaleffectsofhomocysteinefolateandcobalaminonkidneyfunctionamendelianrandomizationstudy AT kimyongchul causaleffectsofhomocysteinefolateandcobalaminonkidneyfunctionamendelianrandomizationstudy AT hanseungseok causaleffectsofhomocysteinefolateandcobalaminonkidneyfunctionamendelianrandomizationstudy AT leehajeong causaleffectsofhomocysteinefolateandcobalaminonkidneyfunctionamendelianrandomizationstudy AT leejungpyo causaleffectsofhomocysteinefolateandcobalaminonkidneyfunctionamendelianrandomizationstudy AT jookwonwook causaleffectsofhomocysteinefolateandcobalaminonkidneyfunctionamendelianrandomizationstudy AT limchunsoo causaleffectsofhomocysteinefolateandcobalaminonkidneyfunctionamendelianrandomizationstudy AT kimyonsu causaleffectsofhomocysteinefolateandcobalaminonkidneyfunctionamendelianrandomizationstudy AT kimdongki causaleffectsofhomocysteinefolateandcobalaminonkidneyfunctionamendelianrandomizationstudy |