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.