{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T01:27:27Z","timestamp":1790386047719,"version":"4.1.0"},"reference-count":34,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,11,26]],"date-time":"2022-11-26T00:00:00Z","timestamp":1669420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"BHF Centre of Excellence Imperial College London","award":["CFC1007"],"award-info":[{"award-number":["CFC1007"]}]},{"name":"UK DRI Ltd.","award":["CFC1007"],"award-info":[{"award-number":["CFC1007"]}]},{"name":"Health Data Research UK","award":["CFC1007"],"award-info":[{"award-number":["CFC1007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Variation in vitamin B12 levels has been associated with a range of diseases across the life-course, the causal nature of which remains elusive. We aimed to interrogate genetically predicted vitamin B12 status in relation to a plethora of clinical outcomes available in the UK Biobank. Genome-wide association study (GWAS) summary data obtained from a Danish and Icelandic cohort of 45,576 individuals were used to identify 8 genetic variants associated with vitamin B12 levels, serving as genetic instruments for vitamin B12 status in subsequent analyses. We conducted a Mendelian randomisation (MR)-phenome-wide association study (PheWAS) of vitamin B12 status with 945 distinct phenotypes in 439,738 individuals from the UK Biobank using these 8 genetic instruments to proxy alterations in vitamin B12 status. We used external GWAS summary statistics for replication of significant findings. Correction for multiple testing was taken into consideration using a 5% false discovery rate (FDR) threshold. MR analysis identified an association between higher genetically predicted vitamin B12 status and lower risk of vitamin B deficiency (including all B vitamin deficiencies), serving as a positive control outcome. We further identified associations between higher genetically predicted vitamin B12 status and a reduced risk of megaloblastic anaemia (OR = 0.35, 95% CI: 0.20\u20130.50) and pernicious anaemia (0.29, 0.19\u20130.45), which was supported in replication analyses. Our study highlights that higher genetically predicted vitamin B12 status is potentially protective of risk of vitamin B12 deficiency associated with pernicious anaemia diagnosis, and reduces risk of megaloblastic anaemia. The potential use of genetically predicted vitamin B12 status in disease diagnosis, progression and management remains to be investigated.<\/jats:p>","DOI":"10.3390\/nu14235031","type":"journal-article","created":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T07:01:30Z","timestamp":1669618890000},"page":"5031","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Associations of Genetically Predicted Vitamin B12 Status across the Phenome"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7591-5684","authenticated-orcid":false,"given":"Marie-Joe","family":"Dib","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London SW7 2BX, UK"},{"name":"British Heart Foundation Centre of Excellence, Imperial College London, London SW7 2BX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kourosh R.","family":"Ahmadi","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, School of Biosciences and Medicine, University of Surrey, Guildford GU2 7XH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7700-8102","authenticated-orcid":false,"given":"Loukas","family":"Zagkos","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London SW7 2BX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7312-7078","authenticated-orcid":false,"given":"Dipender","family":"Gill","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London SW7 2BX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brooke","family":"Morris","sequence":"additional","affiliation":[{"name":"Baylor Biology Department, Baylor University, Waco, TX 76706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Elliott","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London SW7 2BX, UK"},{"name":"British Heart Foundation Centre of Excellence, Imperial College London, London SW7 2BX, UK"},{"name":"Dementia Research Centre, Imperial College London, London SW7 2BX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abbas","family":"Dehghan","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London SW7 2BX, UK"},{"name":"British Heart Foundation Centre of Excellence, Imperial College London, London SW7 2BX, UK"},{"name":"Dementia Research Centre, Imperial College London, London SW7 2BX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4275-9328","authenticated-orcid":false,"given":"Ioanna","family":"Tzoulaki","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London SW7 2BX, UK"},{"name":"British Heart Foundation Centre of Excellence, Imperial College London, London SW7 2BX, UK"},{"name":"Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina 45110, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,26]]},"reference":[{"key":"ref_1","unstructured":"Carmel, R., and Jacobsen, D.W. 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