Educational attainment and offspring birth weight: A bidirectional Mendelian randomization study

Abstract

Background: The association between educational attainment (EA) and offspring birth weight (BW) has been reported by several traditional epidemiological studies. However, evidence for this association tends to be mixed and confounded. This study aimed to investigate the causal association between EA of parents and offspring BW.Methods: Here, we carried out a two-sample bidirectional Mendelian randomization (MR) analysis to examine the causal association between EA of males (n = 131,695) and females (n = 162,028) and offspring BW using genetic instruments. Summary statistics of EA associated single nucleotide polymorphisms (SNPs) were extracted from a GWAS incorporating 293,723 individuals of European descent performed by the Social Science Genetic Association Consortium (SSGAC), and the effects of these SNPs on offspring BW were estimated using a GWAS meta-analysis of 86,577 participants of European descent from 25 studies. Univariable MR analyses were conducted using the inverse-variance weighted (IVW) method and four other methods. Further sensitivity analyses were carried out to test the viability of the results. Multivariable MR was used to examine the confounders between the exposure and outcome.Results: The result shows evidence that the offspring BW is positively causally affected by female EA. Each one standard deviation (SD) increase in female EA was associated with 0.24 SD higher of offspring BW (95% confidence interval [CI], 0.10 to 0.37, p < 0.001 for the IVW method). Similarly, change in offspring BW was 0.21 SD (95% CI: 0.07 to 0.34, p = 2.82 × 10–3) per one SD higher in male EA. No causal effect of BW on EA was found by any of the five methods. The causal association between female EA and offspring BW maintained after adjusting for alcoholic drinks per week and BMI. The effect of male EA on offspring BW was attenuated when we adjusted for BMI and alcoholic drinks per week using multivariable MR analysis.Conclusion: Our study indicated that female EA is positively causally associated with offspring BW. The association between male EA and offspring BW may be confounded by alcoholic drinks per week and BMI.

Mediating Factors in the Association of Maternal Educational Level With Pregnancy Outcomes

“…While a previous MR study observed no association between genetically estimated HDL-C level and offspring birth weight, we observed a negative association; the discrepancy may be explained by our study using updated genetic datasets evaluating many more individuals. We found a positive association between genetically estimated BMI and the risk of gestational diabetes, preeclampsia, and birth weight, as previously observed . We also found that high genetically estimated BMI was associated with an increased risk of ectopic pregnancy, an association that was not present in a previous MR study by Rogne et al due to smaller sample size.…”

“…To our knowledge, only 1 previous MR study has considered the association between educational attainment and a pregnancy outcome. That study found higher genetically estimated educational attainment to be associated with increased birth weight .…”

“…To our knowledge, only 1 previous MR study has considered the association between educational attainment and a pregnancy outcome. That study found higher genetically estimated educational attainment to be associated with increased birth weight . While the investigators did not perform formal mediation analyses, they observed results comparable with those of the main analysis after conducting multivariable MR analyses, including BMI and alcohol consumption.…”

Investigating causal relationships between extensive peripheral immune cell phenotypes and preeclampsia: A bi‐directional Mendelian randomization analysis

“…Furthermore, MR‐Egger regression was employed to detect horizontal pleiotropy among genetic variants. A regression equation intercepting zero or a nonsignificant p ‐value (>.05) for the intercept term implied the absence of average pleiotropic bias 18,20 . Additionally, we applied the MR pleiotropy residual sum and outlier (MR‐PRESSO) methods to identify any outlier SNPs potentially contributing to pleiotropy 21 .…”

“…A regression equation intercepting zero or a nonsignificant p-value (>.05) for the intercept term implied the absence of average pleiotropic bias. 18,20 Additionally, we applied the MR pleiotropy residual sum and outlier (MR-PRESSO) methods to identify any outlier SNPs potentially contributing to pleiotropy. 21 Finally, a leave-one-out analysis was performed to evaluate whether the MR results were strongly driven by a specific SNP.…”