Genome-wide association scans were conducted at each site for all eight traits of interest including the ICV and bilateral volumes of the nucleus accumbens, amyg-dala, caudate nucleus, hippocampus, pallidum, putamen and thalamus. For each SNP in the genome, the additive dosage value was regressed against the trait of interest separately using a multiple linear regression framework controlling for age, age2, sex, 4 MDS components, ICV (for non-ICV phenotypes) and diagnosis (when applicable). For studies with data collected from several centres or scanners, dummy-coded covariates were also included in the model. Sites with family data (NTR-Adults, BrainSCALE, QTIM, SYS, GOBS, ASPSFam, ERF, GeneSTAR, NeuroIMAGE and OATS) used mixed-effects models to control for familial relationships in addition to covariates stated previously. The primary analyses for this paper focused on the full set of subjects including data sets with patients to maximize the power to detect effects. We re-analysed the data excluding patients to verify that detected effects were not due to disease alone (Extended Data Fig. 5a). The protocols used for testing association with mach2qtl (ref. 34) for studies with unrelated subjects
