BD was defined as a composite measure of substance dependence vulnerability (assessed across 10 substances), novelty seeking, and conduct disorder symptoms. The BD phenotype has been previously examined within the CADD samples, including Young et al. (2000) demonstrating that the component measures have loadings ≥0.4 on a common, highly heritable BD latent factor, and linkage analyses by Stallings et al. (2003, 2005). A full description of construction of the BD phenotype is provided in the Supplement; Supplemental Figure S1 shows the distribution of BD in the CADD GWAS sample. Briefly, principal component scores were normed to community-representative samples in CADD and applied to all CADD GWAS participants from both the community-representative (48.2%) and high-risk samples (51.8%). Average scores on the BD composite measure were 0.19 (SD=1.2, range=−1.9–5.0) for the community-representative participants and 2.76 (SD=1.2, range=−0.3–6.7) for the high-risk participants.
