ArticleThe American journal of clinical nutrition2023
Phenome-wide association study of genetically predicted B vitamins and homocysteine biomarkers with multiple health and disease outcomes: analysis of the UK Biobank.
Article in The American journal of clinical nutrition, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Effects of folic acid with vitamin B12/vitamin B6 intervention on serum homocysteine metabolism and complications in patients with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials.Frontiers in nutrition · 2025Pooled it
- Dietary vitamin B6 intake and gallstone prevalence in US adults: A cross-sectional analysis of NHANES 2017-2023.Medicine · 2026Article
- Multi-omics reveals that genes linked to succinylation regulate the onset of epilepsy through metabolic reprogramming.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Article
- CCNE1 Exerts a Protective Effect on Parkinson's Disease by Regulating Ferroptosis-Related Proteins.Brain and behavior · 2025Article
- Integrative multiomics elucidate crotonylation-associated GCDH in Parkinson's disease pathogenesis via metabolome remodeling.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Article
- Clinical implications of bone marrow adiposity identified by phenome-wide association and Mendelian randomization in the UK Biobank.Nature communications · 2025Article
- Mapping the Final Journey: End-Of-Life Frailty Trajectories and Cause of Death.Journal of the American Geriatrics Society · 2025Article
- Mendelian randomization study of micronutrients and development of CKD in a Korean population.Nutrition journal · 2025Article
- Vitamin Status and Risk of Age-Related Diseases Among Adult Residents of the Pearl River Delta Region.Nutrients · 2025Article
- Higher levels of oxidative balance score linked to lower risk of gallstones: findings from the 2017-2020 National Health and Nutrition Examination Survey.Frontiers in nutrition · 2025Article
- Association between oxidative balance score and gallstone disease: a population-based study from NHANES.Frontiers in nutrition · 2025Article
- Genetic homocysteine risk shapes cardiocerebral structure and multimorbidity through age- and sex-specific mechanisms: a UK Biobank study.Frontiers in nutrition · 2025Article
- Association Between Serum Folate Concentrations and 10-Year Stroke Risk in a Prospective Community Cohort: Mediation and Interaction Analyses.Nutrients · 2024Article
- Understanding the Genetic Architecture of Vitamin Status Biomarkers in the Genome-Wide Association Study Era: Biological Insights and Clinical Significance.Advances in nutrition (Bethesda, Md.) · 2024Review
- Cross-sectional studies of the causal link between asthma and osteoporosis: insights from Mendelian randomization and bioinformatics analysis.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2024Article
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Authors and funding
15 authors at 11 institutions in 6 countries.
Funding
Abstract
backgroundAlthough a number of health outcomes such as CVDs, metabolic-related outcomes, neurological disorders, pregnancy outcomes, and cancers have been identified in relation to B vitamins, evidence is of uneven quality and volume, and there is uncertainty about putative causal relationships.
objectivesTo explore the effects of B vitamins and homocysteine on a wide range of health outcomes based on a large biorepository linking biological samples and electronic medical records.
methodsFirst, we performed a phenome-wide association study (PheWAS) to investigate the associations of genetically predicted plasma concentrations (genetic component of the circulating concentrations) of folate, vitamin B6, vitamin B12, and their metabolite homocysteine with a wide range of disease outcomes (including both prevalent and incident events) among 385,917 individuals in the UK Biobank. Second, 2-sample Mendelian randomization (MR) analysis was used to replicate any observed associations and detect causality. We considered MR P <0.05 as significant for replication. Third, dose-response, mediation, and bioinformatics analyses were carried out to examine any nonlinear trends and to disentangle the underlying mediating biological mechanisms for the identified associations.
resultsIn total, 1117 phenotypes were tested in each PheWAS analysis. After multiple corrections, 32 phenotypic associations of B vitamins and homocysteine were identified. Two-sample MR analysis supported that 3 of them were causal, including associations of higher plasma vitamin B6 with lower risk of calculus of kidney (OR: 0.64; 95% CI: 0.42, 0.97; P = 0.033), higher homocysteine concentration with higher risk of hypercholesterolemia (OR: 1.28, 95% CI: 1.04, 1.56; P = 0.018), and chronic kidney disease (OR: 1.32, 95% CI: 1.06, 1.63; P = 0.012). Significant nonlinear dose-response relationships were observed for the associations of folate with anemia, vitamin B12 with vitamin B-complex deficiencies, anemia and cholelithiasis, and homocysteine with cerebrovascular disease.
conclusionsThis study provides strong evidence for the associations of B vitamins and homocysteine with endocrine/metabolic and genitourinary disorders.
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