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dc.contributor.authorMoen, Gunn-Helen
dc.contributor.authorBeaumont, Robin N.
dc.contributor.authorGrarup, Niels
dc.contributor.authorSommer, Christine
dc.contributor.authorShields, Beverley M.
dc.contributor.authorLawlor, Debbie A.
dc.contributor.authorFreathy, Rachel M.
dc.contributor.authorEvans, David M.
dc.contributor.authorWarrington, Nicole Maree
dc.identifier.citationInternational Journal of Epidemiology. 2021, 50 (1), 179-189.en_US
dc.description.abstractBackground Lower maternal serum vitamin B12 (B12) and folate levels have been associated with lower offspring birthweight, in observational studies. The aim of this study was to investigate whether this relationship is causal. Methods We performed two-sample Mendelian randomization (MR) using summary data on associations between genotype-B12 (10 genetic variants) or genotype-folate (four genetic variants) levels from: a genome-wide association study of 45 576 individuals (sample 1); and both maternal- and fetal-specific genetic effects on offspring birthweight from the latest Early Growth Genetics consortium meta-analysis with 297 356 individuals reporting their own birthweight and 210 248 women reporting their offspring's birthweight (sample 2). We used the inverse variance weighted method, and sensitivity analyses to account for pleiotropy, in addition to excluding a potentially pleiotropic variant in the FUT2 gene for B12 levels. Results We did not find evidence for a causal effect of maternal or fetal B12 levels on offspring birthweight. The results were consistent across the different methods. We found a positive causal effect of maternal folate levels on offspring birthweight [0.146 (0.065, 0.227), which corresponds to an increase in birthweight of 71 g per 1 standard deviation higher folate]. We found some evidence for a small inverse effect of fetal folate levels on their own birthweight [−0.051 (−0.100, −0.003)]. Conclusions Our results are consistent with evidence from randomized controlled trials that higher maternal folate levels increase offspring birthweight. We did not find evidence for a causal effect of B12 levels on offspring birthweight, suggesting previous observational studies may have been confounded.en_US
dc.publisherOxford Academicen_US
dc.rightsNavngivelse 4.0 Internasjonal*
dc.titleInvestigating the causal effect of maternal vitamin B12 and folate levels on offspring birthweighten_US
dc.typePeer revieweden_US
dc.typeJournal articleen_US
dc.source.journalInternational Journal of Epidemiologyen_US
dc.description.localcodeThis is an open access article distributed under the terms of the Creative Commons CC BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en_US

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