The advent of the PRS approach has also led to unique answers to additional age-old questions. We now know that genetic liability to SCZ (i.e., PRS) is related to variance in living in urban environments and in neighborhood deprivation, both leading environmental contributors to schizophrenia. Notably, schizophrenia represents an evolutionary paradox (van Dongen and Boomsma, 2013) in that while risk alleles are at selective advantage, the disease is associated with lower reproductive fitness with older paternal age implicated as a risk factor [potentially, due to de novo mutations in the male germ line (Malaspina et al., 2001)]. Yet, SCZ-PRS when applied to a sample of 150, 656 individuals found no correlation with number of children or age at first birth. However, perhaps most sobering is evidence that individuals with higher SCZ-PRS are more likely to drop out of subsequent waves of longitudinal studies, suggesting that distributions of SCZ-PRS, and consequently, their range of related phenotypes, might not be fully represented in cohort data (Martin et al., 2016).
