BACKGROUND AND PURPOSE:

• Observational studies suggest a link between higher maternal blood pressure (BP) during pregnancy and increased risk for cardiometabolic disease in offspring
  • Whether there is a causal mechanism underlying this association is unknown
• Wang et al. (Hypertension, 2021) performed a genetic association study of genotyped mother-offspring pairs to look for relationships between maternal genetic risk scores and cardiometabolic impact on offspring

METHODS:

• Genetic association study using Mendelian randomization (MR) framework
  • MR can be used to estimate causal relationships between an environmental exposure of interest and disease
  • If there was an association between maternal GRSs and offspring outcomes, it would suggest a causal effect of maternal BP on the offspring outcomes
• Population
  • Genotyped mother-offspring pairs from the UK Biobank (UKB) and Trøndelag Health Study (HUNT) study
  • All dyads were of European ancestry
  • All offspring from the UKB and the majority of offspring from the HUNT study are ≥middle-age and would be manifest primary outcomes if present
• Exposure
  • Maternal genetic risk score (GRSs) – SNPs associated with maternal BP
    • SNPs were identified from external genome wide association studies and validated on the study population
    • Strong evidence that the unweighted maternal genetic scores of BP variants were positively associated with higher maternal blood pressure during pregnancy
• Study design
  • The authors tested the association between maternal genetic scores from BP-associated SNPs and offspring outcomes
  • If there was an association between maternal GRSs and offspring outcomes, it would suggest a causal effect of maternal BP on the offspring outcomes
  • Power calculations: ≥80% power to detect a maternal genetic effect that explained as little as 0.035% of the variance in the offspring cardiometabolic trait 
• Primary outcomes
  • Offspring cardiometabolic risk factors for cardiometabolic disease
    • Systolic and diastolic BP
    • BMI
    • Lipid profile
    • Glycemic biomarkers

RESULTS:

• Mother-offspring pairs: 29,708 | Father-offspring pairs: 21,423
• There was no association between maternal unweighted genetic scores and cardiometabolic offspring outcomes
• Outcome example: Association between maternal systolic BP genetic score and offspring BMI
  • UK Biobank: P=0.0580
  • HUNT: P=0.646
  • Meta-analysis: P=0.2552
• There was also no association with paternal genetic scores

CONCLUSION:

• There were no associations between maternal genetic risk scores for BP and offspring cardiometabolic outcomes
• Maternal BP during pregnancy is probably not a major risk factor for offspring cardiometabolic disease
• Authors acknowledge multiple limitations and that further genetic studies are required for extreme BP exposures such as preeclampsia
• The authors state:

Our study suggests that high maternal blood pressure, as proxied by maternal SNPs that influence blood pressure is unlikely to be a key determinant of adverse cardiometabolic outcomes in offspring

Learn More – Primary Sources:

Investigating a Potential Causal Relationship Between Maternal Blood Pressure During Pregnancy and Future Offspring Cardiometabolic Health

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