The effect of maternal BMI, smoking and alcohol on congenital heart diseases: a Mendelian randomisation study

Area of Science:

• Genetics
• Epidemiology
• Public Health

Background:

• Congenital heart diseases (CHDs) are a major cause of infant illness and death.
• While maternal risk factors are studied, genetic epidemiology methods for causal inference are underutilized.
• Understanding genetic and environmental influences on CHDs is crucial for prevention.

Purpose of the Study:

• To investigate the causal effects of genetically predicted maternal body mass index (BMI), smoking, and alcohol consumption on offspring congenital heart diseases (CHDs).
• To apply Mendelian randomization (MR) methods to enhance causal inference in the study of maternal risk factors for CHDs.
• To assess the association between maternal lifestyle factors and CHD risk using large birth cohort data.

Main Methods:

• Utilized three birth cohorts comprising 65,510 mother/offspring pairs with 562 CHD cases.
• Employed Mendelian randomization (MR) analyses with genetic risk scores (GRS) derived from genome-wide association studies (GWAS).
• Conducted logistic regression and random-effects meta-analyses, including multivariable MR for sensitivity analyses.

Main Results:

• Genetic risk scores (GRS) for maternal BMI, smoking, and alcohol consumption were associated with exposures during pregnancy.
• Pooled odds ratios for offspring CHD per 1 SD higher GRS were close to the null for BMI (0.95), smoking (1.01), and alcohol (1.06).
• Sensitivity analyses confirmed the robustness of these null findings.

Conclusions:

• The study did not find robust evidence linking maternal BMI, smoking, or alcohol consumption to offspring CHDs.
• Results were imprecise, indicating a need for replication in larger, more comprehensive studies.
• Future research should include maternal and offspring genotype data alongside offspring CHD information for stronger causal inference.