Bipolar disorder subtypes. We obtained access to individual genotype data from 55 bipolar disorder cohorts collected by the PGC Bipolar Disorder Working group (
Pseudo subtypes of paired major diseases. We obtained previously published GWAS summary statistics for four major diseases: type 2 diabetes, coronary artery disease, obesity (defined as body mass index > 30) and hypercholesterolemia (defined as low-density lipoproteins > 4.9 mmol/L) and performed a meta-analysis for each pair of traits. Meta-analyses were performed using METAL [58 (link)] with the sample-size weighted fixed-effects algorithm. To truly mimic a composite phenotype GWAS, only variants included in both GWAS summary statistics were retained. The resulting meta-analysis summary statistics were used as base sample. As target sample, we generated composite phenotypes by combining cases of the two paired phenotypes using UK Biobank. To calculate the PRS, target sample phenotypes were encoded mimicking sub-phenotypes of a given disease, for example, for the phenotype coronary artery disease-obesity, samples with coronary artery disease (and not obesity) were coded as 0 and those with obesity (and not coronary artery disease) were coded as 1 (
Comorbid subtypes of major diseases. For the analysis of subtypes with presence/absence of comorbid diseases, we used type 2 diabetes, coronary artery disease, obesity, hypertension and hypercholesterolemia, as these diseases present high comorbidity between them (