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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...

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Autores principales: 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
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
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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.
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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
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