Introduction: Complex traits are determined by both genetic and environmental factors,
as well as by their interactions (GxE). Maternal smoking during pregnancy is one of the
most relevant exposures with both short- and long-term health effects in the mother and
the new-born. The identification of genetic factors of complex ...»»»»
Introduction: Complex traits are determined by both genetic and environmental factors,
as well as by their interactions (GxE). Maternal smoking during pregnancy is one of the
most relevant exposures with both short- and long-term health effects in the mother and
the new-born. The identification of genetic factors of complex traits has been transformed
during the last decades thanks to genome-wide association studies (GWAS), which can
be used to predict individuals’ disease risk through the calculation of polygenic risk scores
(PRSs). A PRS is defined as a number that summarises the estimated effect of many
genetic variants on an individual’s phenotype.
Objective: In this study we aimed, first, to compute and validate PRSs for common traits
for children of the Human Early Life Exposome (HELIX) project, and second, to test the
interaction between maternal smoking during pregnancy and these PRSs (GxE).
Methods: PRSs for a total of 42 common traits were calculated for 1155 children of
European ancestry from the HELIX project using the PRSice-v2 tool accounting for
linkage disequilibrium. 10 PRSs with a different number of single nucleotide
polymorphisms (SNPs) were calculated. For 23 traits measured in HELIX, we tested their
association with the PRS, also using PRSice-v2. The PRS with the highest R2 fit of the
model was considered the best PRS and followed in the GxE analyses. The association
between maternal smoking during pregnancy and 10 selected traits was tested using linear
regression models adjusted for covariates. GxE interactions between maternal smoking
during pregnancy and the PRSs were tested by including and interaction term in the
models.
Results: Out of the 23 PRSs tested for validation, 17 showed significant relationships
with the phenotypic trait. However, the proportion of the variance explained by the PRS
was very small (maximum 4.9%). In line with other studies, mothers that smoked during
pregnancy had new-borns with lower birth weight, higher body mass index, and higher
waist circumference. Effects were stronger in offspring of sustained smoker mothers than
in non-sustained smokers. We did not detect any significant GxE interaction between
maternal smoking in pregnancy and the PRSs, likely due to the limited sample size and
variance explained by the PRSs. However, a marginal trend was found for birth weight,
where children within the third tertile of the birth weight PRS were protected against the
adverse effects of sustained smoking during pregnancy in comparison to children in the
other two tertiles.
Conclusion: A total of 42 PRSs were calculated for HELIX children, which 17 of them
were associated with their phenotypic trait explaining a small proportion of it. We could
not find any interaction between maternal smoking and the PRSs, except for a marginal
trend for birth weight.^^^^
