Gunn-Helen Moen1,2, Elisabeth Qvigstad1, Kåre I Birkeland1,2,3, David M Evans4,5, Christine Sommer1. 1. Department of Endocrinology, Morbid Obesity, and Preventive Medicine, Oslo University Hospital, Oslo, Norway. 2. Faculty of Medicine, University of Oslo, Institute of Clinical Medicine, Oslo, Norway. 3. Department of Transplantation Medicine, Institute of Clinical Medicine, University of Oslo and Oslo University Hospital, Oslo, Norway. 4. University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia. 5. Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
Abstract
Background: Several observational studies have shown that low serum vitamin B-12 is associated with increased body mass index (BMI) and adverse cardiometabolic outcomes. However, it is unclear if these associations reflect a causal effect of vitamin B-12 on cardiometabolic risk factors and diseases, latent confounding, or reverse causality. Objectives: The aims of this study were to investigate 1) the possible causal relation between vitamin B-12 and indicators of body fat, lipid, and glucose variables; type 2 diabetes (T2D); and cardiovascular disease by using a 2-sample Mendelian randomization (MR) method and 2) the possible pleiotropic role of fucosyltransferase 2 (FUT2). Design: We selected 11 single nucleotide polymorphisms (SNPs) robustly associated with serum concentrations of vitamin B-12 in a previous genomewide association study (GWAS) in 45,576 individuals. We performed 2-sample MR analyses of the relation between vitamin B-12 and cardiometabolic risk factors and diseases with the use of publicly available GWAS summary statistics for 15 outcomes in ≤339,224 individuals. The robustness of results was tested with sensitivity analyses by using MR Egger regression and weighted-median estimation, and by performing additional analyses excluding a variant in the FUT2 gene, which may be pleiotropic. Results: We found a suggestive causal relation between vitamin B-12 and fasting glucose and β cell function [homeostatic model assessment (HOMA) of β cell function (HOMA-B)]. However, we found no evidence that serum concentrations of vitamin B-12 were causally related to BMI, waist-to-hip ratio, plasma leptin, body fat, fasting insulin, insulin resistance (from HOMA of insulin resistance), glycated hemoglobin, triglycerides, T2D, coronary artery disease, or HDL, LDL, or total cholesterol. Conclusions: We found no evidence that serum concentrations of vitamin B-12 are causally related to body weight or the majority of cardiometabolic outcomes investigated. However, vitamin B-12 may have a causal effect on fasting glucose and HOMA-B, although these results will require replication in large independent data sets. This trialwas registered at http://www.isrctn.com/ISRCTN47414943 as ISRCTN47414943.
Background: Several observational studies have shown that low serum vitamin B-12 is associated with increased body mass index (BMI) and adverse cardiometabolic outcomes. However, it is unclear if these associations reflect a causal effect of vitamin B-12 on cardiometabolic risk factors and diseases, latent confounding, or reverse causality. Objectives: The aims of this study were to investigate 1) the possible causal relation between vitamin B-12 and indicators of body fat, lipid, and glucose variables; type 2 diabetes (T2D); and cardiovascular disease by using a 2-sample Mendelian randomization (MR) method and 2) the possible pleiotropic role of fucosyltransferase 2 (FUT2). Design: We selected 11 single nucleotide polymorphisms (SNPs) robustly associated with serum concentrations of vitamin B-12 in a previous genomewide association study (GWAS) in 45,576 individuals. We performed 2-sample MR analyses of the relation between vitamin B-12 and cardiometabolic risk factors and diseases with the use of publicly available GWAS summary statistics for 15 outcomes in ≤339,224 individuals. The robustness of results was tested with sensitivity analyses by using MR Egger regression and weighted-median estimation, and by performing additional analyses excluding a variant in the FUT2 gene, which may be pleiotropic. Results: We found a suggestive causal relation between vitamin B-12 and fasting glucose and β cell function [homeostatic model assessment (HOMA) of β cell function (HOMA-B)]. However, we found no evidence that serum concentrations of vitamin B-12 were causally related to BMI, waist-to-hip ratio, plasma leptin, body fat, fasting insulin, insulin resistance (from HOMA of insulin resistance), glycated hemoglobin, triglycerides, T2D, coronary artery disease, or HDL, LDL, or total cholesterol. Conclusions: We found no evidence that serum concentrations of vitamin B-12 are causally related to body weight or the majority of cardiometabolic outcomes investigated. However, vitamin B-12 may have a causal effect on fasting glucose and HOMA-B, although these results will require replication in large independent data sets. This trialwas registered at http://www.isrctn.com/ISRCTN47414943 as ISRCTN47414943.
Authors: Gunn-Helen Moen; Robin N Beaumont; Niels Grarup; Christine Sommer; Beverley M Shields; Deborah A Lawlor; Rachel M Freathy; David M Evans; Nicole M Warrington Journal: Int J Epidemiol Date: 2021-03-03 Impact factor: 9.685
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Authors: Peitao Wu; Denis Rybin; Lawrence F Bielak; Mary F Feitosa; Nora Franceschini; Yize Li; Yingchang Lu; Jonathan Marten; Solomon K Musani; Raymond Noordam; Sridharan Raghavan; Lynda M Rose; Karen Schwander; Albert V Smith; Salman M Tajuddin; Dina Vojinovic; Najaf Amin; Donna K Arnett; Erwin P Bottinger; Ayse Demirkan; Jose C Florez; Mohsen Ghanbari; Tamara B Harris; Lenore J Launer; Jingmin Liu; Jun Liu; Dennis O Mook-Kanamori; Alison D Murray; Mike A Nalls; Patricia A Peyser; André G Uitterlinden; Trudy Voortman; Claude Bouchard; Daniel Chasman; Adolfo Correa; Renée de Mutsert; Michele K Evans; Vilmundur Gudnason; Caroline Hayward; Linda Kao; Sharon L R Kardia; Charles Kooperberg; Ruth J F Loos; Michael M Province; Tuomo Rankinen; Susan Redline; Paul M Ridker; Jerome I Rotter; David Siscovick; Blair H Smith; Cornelia van Duijn; Alan B Zonderman; D C Rao; James G Wilson; Josée Dupuis; James B Meigs; Ching-Ti Liu; Jason L Vassy Journal: PLoS One Date: 2020-05-07 Impact factor: 3.752