期刊
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
卷 50, 期 1, 页码 179-189出版社
OXFORD UNIV PRESS
DOI: 10.1093/ije/dyaa256
关键词
Maternal genetic effect; fetal genetic effect; vitamin B12; folate; birthweight; Mendelian randomization
资金
- Australian Government
- Norwegian Diabetes Association
- Nils Normans minnegave
- Norwegian Research Council [287198]
- Australian National Health and Medical Research Council Senior Research Fellowship [APP1137714]
- NHMRC [GNT1125200, GNT1157714]
- Sir Henry Dale Fellowship (Wellcome Trust)
- Royal Society [WT104150, 104150/Z/14/Z]
- Australian National Health and Medical Research Council Early Career Fellowship [APP1104818]
- European Research Council [669545]
- US National Institute for Health [R01 DK10324]
- UK National Institute of Health Research [NF-0616-10102]
- University of Bristol
- UK Medical Research Council [MC_ UU_00011/6]
- South West NHS Research and Development
- Exeter NHS Research and Development
- Darlington Trust
- Peninsula National Institute of Health Research (NIHR) Clinical Research Facility at the University of Exeter
- Wellcome Trust
- Novo Nordisk Foundation [NNF18CC0034900]
- MRC [MC_UU_12013/4, MC_UU_00011/6] Funding Source: UKRI
This study found a positive causal effect of maternal folate levels on offspring birthweight, while no causal effect of B12 levels on offspring birthweight was observed. The results are consistent with evidence from randomized controlled trials.
Background: 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.
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