Chunk #28 — Polygenic Risk Scores: A Bridge Between Population Variation and Individual Differences — PRS Practicalities — Technical Considerations. — Improvements in Discovery GWAS:
al., 2013). The potential implications of GWAS phenotyping may be observed when contrasting two GWAS of depression. In the larger study, which contained 9,240 MDD cases and 9,519 controls, no genomewide significant loci were detected (Major Depressive Disorder Working Group of the Psychiatric et al., 2013). The second study which consisted of Han Chinese women with recurrent, primarily melancholic, depression (n=5,303) or without MDD (n=5,337), identified 2 genomewide significant loci (CONVERGE, 2015), including one within a candidate gene, SIRT1, which has been previously linked to reward-related neural and behavioral phenotypes in non-human animal models, as well as anxiety and age-related disease and mortality (Libert et al., 2011, Kishi et al., 2010, Kuningas et al., 2007). Arguably, the phenotypic and population homogeneity of the CONVERGE effort resulted in relatively improved power (Sullivan, 2015). Notably, however, other large scale GWAS of even more heterogenous phenotypes (e.g., those self-reporting a depression diagnosis through 23andMe) have also been met with success (Hyde et al., 2016). Further, other evidence suggests that traditionally conceptualized intermediate phenotypes (e.g., brain volume), may not be associated with larger effects related to common genetic variation suggesting potential limitations to “deeper” phenotyping (Franke et al., 2016). Going forward it will be
