SynthesisPLoS genetics2013
Genetic architecture of vitamin B12 and folate levels uncovered applying deeply sequenced large datasets.
Synthesis in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers, 8 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
112 citing papers in PubMed, 8 syntheses or guidelines pooled it, 181 citations in OpenAlex.
- A meta-analysis of epigenome-wide association studies on pregnancy vitamin B12 concentrations and offspring DNA methylation.Epigenetics · 2023Pooled it
- Investigating Causal Associations of Circulating Micronutrients Concentrations with the Risk of Lung Cancer: A Mendelian Randomization Study.Nutrients · 2022Pooled it
- Investigating the causal effect of maternal vitamin B12 and folate levels on offspring birthweight.International journal of epidemiology · 2021Pooled it
- Genetic Variants Shaping Inter-individual Differences in Response to Dietary Intakes-A Narrative Review of the Case of Vitamins.Frontiers in nutrition · 2020Pooled it
- Genome-wide association meta-analysis yields 20 loci associated with gallstone disease.Nature communications · 2018Pooled it
- Associations of genetic determinants of serum vitamin B12 and folate concentrations with hay fever and asthma: a Mendelian randomization meta-analysis.European journal of clinical nutrition · 2018Pooled it
- Meta-Prediction of the Effect of Methylenetetrahydrofolate Reductase Polymorphisms and Air Pollution on Alzheimer's Disease Risk.International journal of environmental research and public health · 2017Pooled it
- A genome-wide association meta-analysis of diarrhoeal disease in young children identifies FUT2 locus and provides plausible biological pathways.Human molecular genetics · 2016Pooled it
- Genetic Variation in Response to the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND): A Randomized Controlled Trial.Nutrients · 2026Trial
- The Oral Bioavailability of Vitamin BNutrients · 2024Trial
- Homocysteine Metabolism Gene Polymorphisms (MTHFR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G) Jointly Elevate the Risk of Folate Deficiency.Nutrients · 2015Trial
- Exome sequencing and analysis of 44,028 British South Asians enriched for high autozygosity.Nature genetics · 2026Article
- Identification of a genetic risk factor for metformin-induced vitamin BDiabetologia · 2026Article
- Study on the expression level of folate receptor γ in thyroid cancer and its association with clinicopathological characteristics.Oncology letters · 2026Article
- Genetically Predicted Homocysteine Levels and B Vitamins on Sarcopenia-Related Traits: Insights From an Observational and Mendelian Randomization Analysis.Food science & nutrition · 2026Article
- Influence of Transcobalamin II (TCN2) and its receptor (CD320) gene polymorphisms on circulating TCN2 and CD320 levels in individuals with vitamin B12 deficiency.Irish journal of medical science · 2025Article
- Folate Attenuates Ulcerative Colitis via PI3K/AKT/NF-κB/MLCK Axis Inhibition to Restore Intestinal Barrier Integrity.Biology · 2025Article
- Causal Associations of Circulating Micronutrients With the Risk of Infertility: A Mendelian Randomization Study.Food science & nutrition · 2025Article
- Association of Vitamins and Minerals with Type 1 Diabetes Risk: A Mendelian Randomization Study.Nutrients · 2025Article
- Unraveling folate deficiency: prevalence, biochemical associations, genetic determinants, and strategies for adolescent health in North India.European journal of clinical nutrition · 2025Article
52 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
30 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genome-wide association studies have mainly relied on common HapMap sequence variations. Recently, sequencing approaches have allowed analysis of low frequency and rare variants in conjunction with common variants, thereby improving the search for functional variants and thus the understanding of the underlying biology of human traits and diseases. Here, we used a large Icelandic whole genome sequence dataset combined with Danish exome sequence data to gain insight into the genetic architecture of serum levels of vitamin B(12) (B12) and folate. Up to 22.9 million sequence variants were analyzed in combined samples of 45,576 and 37,341 individuals with serum B(12) and folate measurements, respectively. We found six novel loci associating with serum B(12) (CD320, TCN2, ABCD4, MMAA, MMACHC) or folate levels (FOLR3) and confirmed seven loci for these traits (TCN1, FUT6, FUT2, CUBN, CLYBL, MUT, MTHFR). Conditional analyses established that four loci contain additional independent signals. Interestingly, 13 of the 18 identified variants were coding and 11 of the 13 target genes have known functions related to B(12) and folate pathways. Contrary to epidemiological studies we did not find consistent association of the variants with cardiovascular diseases, cancers or Alzheimer's disease although some variants demonstrated pleiotropic effects. Although to some degree impeded by low statistical power for some of these conditions, these data suggest that sequence variants that contribute to the population diversity in serum B(12) or folate levels do not modify the risk of developing these conditions. Yet, the study demonstrates the value of combining whole genome and exome sequencing approaches to ascertain the genetic and molecular architectures underlying quantitative trait associations.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.