Genome-wide association studies in neuropsychiatric disorders tend to produce small effect sizes; even the most significantly associated markers tend to have small effects, with odds ratios (OR) in the range of 0.8–1.2. These small effect sizes, and the resultant lack of power, mean that the majority of disease associated SNPs fall below genome-wide significance; markers rejected by GWAS can be combined into quantitative scores to examine the combined effects of the variants [32,33]. We calculated polygenic risk scores (PRS) using PRSice [34]. PRSice calculates the best-fit PRS across 10,000 thresholds (from PT = 0.0001 to PT = 0.5 by increments of 0.00005) by regressing phenotype on score and two ancestry informative covariates. To calculate PRS in this study, we used publicly available GWAS results as base datasets; these are the five most recent analyses by the Psychiatric Genomics Consortium (PGC)—schizophrenia, depression, ADHD, autism and bipolar disorder [35–39]–and four phenotypes from the Tobacco And Genetics Consortium—ever smoked, quantities of cigarettes smoked, former smoker and age at starting smoking [40].
