Interpretation:
The genetics of PA is difficult to study given the clinical ambiguity of
the diagnosis and research towards this realm has been limited.
Acknowledging the inherent limitations of population-based studies, the
ability to evaluate a large cohort of people with multiple pregnancies
is valuable in estimating an individuals’ inherited risk of PA. We
estimated 18-20% as the inherited increase in odds for PA in FDRs,
which is similar to the results of a smaller study performed in Norway.
Rasmussen et. al (2009) performed a population-based study including
greater than 160,000 families and estimated the heritability among FDRs
to be 16%. 10 Our estimates for SDRs and TDRs, 9%
and 0-1% respectively, reveal a strong argument for the presence of
genetic changes shared among relatives with declining heritability for
more distantly related individuals in a pedigree. At the third-degree
level, the estimated heritability is equivalent to the suspected
baseline risk of PA in the US population of 1-2%.1–3 An elevated odds of PA was estimated for the
highest risk individuals, or individuals who experienced two or more
PAs, which further supports the hypothesis that shared genetic changes
may predispose to PA occurrence. After adjusting for possibly
confounding clinical risk factors with the ego-driven familial analyses,
the effect estimates were noted to be lower than those without
considering these risk factors, which raises the suspicion of shared
environments among family members.