{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T02:13:40Z","timestamp":1782526420627,"version":"3.54.5"},"reference-count":36,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T00:00:00Z","timestamp":1615420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003052","name":"Ministry of Trade, Industry and Energy","doi-asserted-by":"publisher","award":["10077474"],"award-info":[{"award-number":["10077474"]}],"id":[{"id":"10.13039\/501100003052","id-type":"DOI","asserted-by":"publisher"}]},{"name":"SNU R&amp;DB Foundation","award":["800-20190571"],"award-info":[{"award-number":["800-20190571"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>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 \u22120.95 (\u22121.21, \u22120.69) %), 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 (\u22120.11 (\u22120.33, 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.<\/jats:p>","DOI":"10.3390\/nu13030906","type":"journal-article","created":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T05:38:22Z","timestamp":1615441102000},"page":"906","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Causal Effects of Homocysteine, Folate, and Cobalamin on Kidney Function: A Mendelian Randomization Study"],"prefix":"10.3390","volume":"13","author":[{"given":"Sehoon","family":"Park","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea"},{"name":"Department of Internal Medicine, Armed Forces Capital Hospital, Gyeonggi-do 13574, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soojin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Korea"},{"name":"Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1596-1528","authenticated-orcid":false,"given":"Yaerim","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Keimyung University School of Medicine, Daegu 42601, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Semin","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Korea"},{"name":"Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4586-5062","authenticated-orcid":false,"given":"Kwangsoo","family":"Kim","sequence":"additional","affiliation":[{"name":"Transdisciplinary Department of Medicine &amp; Advanced Technology, Seoul National University Hospital, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3215-8681","authenticated-orcid":false,"given":"Yong Chul","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Seok","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Korea"},{"name":"Kidney Research Institute, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1873-1587","authenticated-orcid":false,"given":"Hajeong","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Pyo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Korea"},{"name":"Kidney Research Institute, Seoul National University, Seoul 08826, Korea"},{"name":"Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul 07061, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwon Wook","family":"Joo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Korea"},{"name":"Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Korea"},{"name":"Kidney Research Institute, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun Soo","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Korea"},{"name":"Kidney Research Institute, Seoul National University, Seoul 08826, Korea"},{"name":"Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul 07061, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yon Su","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea"},{"name":"Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Korea"},{"name":"Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Korea"},{"name":"Kidney Research Institute, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Ki","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Korea"},{"name":"Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Korea"},{"name":"Kidney Research Institute, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/S0140-6736(20)30045-3","article-title":"Global, regional, and national burden of chronic kidney disease, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017","volume":"395","author":"Bikbov","year":"2020","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"94","DOI":"10.7326\/0003-4819-140-2-200401200-00009","article-title":"Elevated plasma homocysteine level is an independent predictor of coronary heart disease events in patients with type 2 diabetes mellitus","volume":"140","author":"Soinio","year":"2004","journal-title":"Ann. 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