LD score regression37 was used to evaluated the relative contribution of polygenic effects and confounding factors, such as cryptic relatedness and population stratification, to deviation from the null in the genome-wide distribution of GWAS χ2 statistics. Analysis was performed using pre-computed LD scores from European-ancestry samples in the 1000 Genomes Project (see URLs) and summary statistics for the European-ancestry ADHD GWAS to ensure matching of population LD structure. The influence of confounding factors was tested by comparing the estimated intercept of the LD score regression to one, it’s expected value under the null hypothesis of no confounding from e.g. population stratification. The ratio between this deviation and the deviation of the mean χ2 from one (i.e. it’s expected value under the null hypothesis of no association) was used to estimate the proportion of inflation in χ2 attributable to confounding as opposed to true polygenic effects (ratio = (intercept-1)/(mean χ2-1)). SNP heritability was estimated based on the slope of the LD score regression, with heritability on the liability scale calculated assuming a 5% population prevalence of ADHD39.
