in studies exploring relationships with the immune system due to the overrepresentation of immune function loci in SCZ GWAS (Schizophrenia Working Group of the Psychiatric Genomics, 2014). For example, SCZ-PRS have been leveraged to test novel immune-related hypotheses with one study finding no evidence that SCZ-PRS moderates the relationship between infection and schizophrenia (Benros et al., 2016). Going forward, system-based PRS composition (i.e., forming a PRS from SNPs within biologically-defined pathways) may be particularly useful in this regard (see Improving PRS section below). Studies on health-related phenotypes also highlight several novel genetic relationships that transform our understanding of the relationship between schizophrenia, health and disease, ranging from self-rated health (Harris et al., 2016) to chronic and debilitating conditions such as migraines (Van der Auwera et al., 2016) and farther, to rare but serious progressive neurodegenerative disorders like Amyotrophic Lateral Sclerosis (ALS, Lou Gehrig’s Disease (McLaughlin et al., 2017). Prior to the development of the PRS approach, the notion that the genetic underpinnings of such health-related conditions could overlap with predisposition to psychiatric disorders seemed to be an insurmountable challenge to address, particularly for uncommon conditions (e.g., SCZ, ALS) that make family-based approaches impractical.
