summarizing genetic risk of anxiety. To derive a PRS for neuroticism we used GWAS summary stats of a weighted neuroticism sum-score, constructed by adding up ten individual item responses (Fed-up, Guilt, Irr, Miss, Mood, Tense, Nerv feel, Suf Nerv, worry emb and worry) by Nagel et al.120. In addition, we calculated PRSs using the following GWAS summary stats for traits related to substance-use and substance-use-disorder as training datasets. These include cannabis use disorder39(excluding iPSYCH samples, i.e., training only based on data from PGC and data from decode genetics), cannabis use114, alcohol dependence115, drinks per week, smoking ever116, age of initiation as a regular smoker, current versus a former smoker (smoking cessation), number of cigarettes per day, smoking initiation117. All summary statistics were combined in a pseudo-meta-analysis, using the a fixed-effects variance-weighted meta-analysis implemented in METAL28, to generate a SUD-PRS summarizing genetic liability of substance use disorder.
