Estimating effects of serum vitamin B12 levels on psychiatric disorders and cognitive impairment: a Mendelian randomization study
Abstract Background Vitamin B12 deficiency can lead to pernicious anemia and has been associated with various neuropsychiatric diseases and cognitive decline. However, it is unclear whether increasing serum vitamin B12 levels can help to prevent the onset of psychiatric disorders and cognitive impai...
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Nature Portfolio
2025-07-01
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| Series: | Communications Medicine |
| Online Access: | https://doi.org/10.1038/s43856-025-01043-x |
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| author | Tianyuan Lu Andrew D. Paterson |
| author_facet | Tianyuan Lu Andrew D. Paterson |
| author_sort | Tianyuan Lu |
| collection | DOAJ |
| description | Abstract Background Vitamin B12 deficiency can lead to pernicious anemia and has been associated with various neuropsychiatric diseases and cognitive decline. However, it is unclear whether increasing serum vitamin B12 levels can help to prevent the onset of psychiatric disorders and cognitive impairment in the general population. Methods Leveraging large-scale genome-wide association studies (GWASs), we conducted Mendelian randomization (MR) and sensitivity analyses to estimate the potential effects of serum vitamin B12 levels on eight psychiatric disorders, educational attainment and cognitive performance. We conducted additional MR analyses utilizing within-sibship studies to mitigate potential residual confounding effects. Results As a positive control, we confirm that a one standard deviation increase in genetically increased vitamin B12 levels is strongly protective against pernicious anemia (odds ratio, OR = 0.24; 95% CI: 0.15–0.40; p-value = 2.1×10-8). In contrast, MR estimates of vitamin B12 effects on all eight psychiatric disorders, educational attainment and cognitive performance largely overlap with the null. For example, a one standard deviation increase in genetically predicted vitamin B12 levels is associated with an OR of 1.02 for depression (95% CI: 1.00 – 1.04; p-value = 0.11), a 0.0077 standard deviation increase in educational attainment (95% CI: −0.010 – 0.025; p-value = 0.39) and a 0.013 standard deviation increase in cognitive performance (95% CI: −0.0088 – 0.035; p-value = 0.24). No significant associations are identified in sensitivity analyses excluding pleiotropic genetic instruments or MR analyses based on within-sibship studies. Conclusions Our findings suggest that increasing overall vitamin B12 levels may not meaningfully protect against the investigated psychiatric disorders or cognitive impairment in the general population. |
| format | Article |
| id | doaj-art-35b1ed3f727a489a831aa829ce2c4028 |
| institution | Kabale University |
| issn | 2730-664X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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| series | Communications Medicine |
| spelling | doaj-art-35b1ed3f727a489a831aa829ce2c40282025-08-20T03:46:16ZengNature PortfolioCommunications Medicine2730-664X2025-07-01511810.1038/s43856-025-01043-xEstimating effects of serum vitamin B12 levels on psychiatric disorders and cognitive impairment: a Mendelian randomization studyTianyuan Lu0Andrew D. Paterson1Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-MadisonDivision of Biostatistics, Dalla Lana School of Public Health, University of TorontoAbstract Background Vitamin B12 deficiency can lead to pernicious anemia and has been associated with various neuropsychiatric diseases and cognitive decline. However, it is unclear whether increasing serum vitamin B12 levels can help to prevent the onset of psychiatric disorders and cognitive impairment in the general population. Methods Leveraging large-scale genome-wide association studies (GWASs), we conducted Mendelian randomization (MR) and sensitivity analyses to estimate the potential effects of serum vitamin B12 levels on eight psychiatric disorders, educational attainment and cognitive performance. We conducted additional MR analyses utilizing within-sibship studies to mitigate potential residual confounding effects. Results As a positive control, we confirm that a one standard deviation increase in genetically increased vitamin B12 levels is strongly protective against pernicious anemia (odds ratio, OR = 0.24; 95% CI: 0.15–0.40; p-value = 2.1×10-8). In contrast, MR estimates of vitamin B12 effects on all eight psychiatric disorders, educational attainment and cognitive performance largely overlap with the null. For example, a one standard deviation increase in genetically predicted vitamin B12 levels is associated with an OR of 1.02 for depression (95% CI: 1.00 – 1.04; p-value = 0.11), a 0.0077 standard deviation increase in educational attainment (95% CI: −0.010 – 0.025; p-value = 0.39) and a 0.013 standard deviation increase in cognitive performance (95% CI: −0.0088 – 0.035; p-value = 0.24). No significant associations are identified in sensitivity analyses excluding pleiotropic genetic instruments or MR analyses based on within-sibship studies. Conclusions Our findings suggest that increasing overall vitamin B12 levels may not meaningfully protect against the investigated psychiatric disorders or cognitive impairment in the general population.https://doi.org/10.1038/s43856-025-01043-x |
| spellingShingle | Tianyuan Lu Andrew D. Paterson Estimating effects of serum vitamin B12 levels on psychiatric disorders and cognitive impairment: a Mendelian randomization study Communications Medicine |
| title | Estimating effects of serum vitamin B12 levels on psychiatric disorders and cognitive impairment: a Mendelian randomization study |
| title_full | Estimating effects of serum vitamin B12 levels on psychiatric disorders and cognitive impairment: a Mendelian randomization study |
| title_fullStr | Estimating effects of serum vitamin B12 levels on psychiatric disorders and cognitive impairment: a Mendelian randomization study |
| title_full_unstemmed | Estimating effects of serum vitamin B12 levels on psychiatric disorders and cognitive impairment: a Mendelian randomization study |
| title_short | Estimating effects of serum vitamin B12 levels on psychiatric disorders and cognitive impairment: a Mendelian randomization study |
| title_sort | estimating effects of serum vitamin b12 levels on psychiatric disorders and cognitive impairment a mendelian randomization study |
| url | https://doi.org/10.1038/s43856-025-01043-x |
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