28A single dimension of general psychopathology, p, has been hypothesized to represent a general 29 liability that spans multiple types of psychiatric disorders and non-clinical variation in psychiatric 30 symptoms across the lifespan. We conducted genome-wide association analyses of lifetime 31 symptoms of mania, psychosis, irritability in 124,952 to 208,315 individuals from UK Biobank, 32 and then applied Genomic SEM to model the genetic relationships between these psychiatric 33 symptoms and clinically-defined psychiatric disorders (schizophrenia, bipolar disorder, major 34 depressive disorder). Two dimensions of cross-cutting genetic liability emerged: general 35 vulnerability to self-reported symptoms (p self ) versus transdiagnostic vulnerability to clinically-36 diagnosed disease (p clinician ). These were only modestly correlated (r g = .344). Multivariate GWAS 37 identified 145 and 11 independent and genome-wide significant loci for p clinician and p self , 38 respectively, and improved polygenic prediction, relative to univariate GWAS, in hold-out 39 samples. Despite the severe impairments in occupational and educational functioning seen in 40 patients with schizophrenia and bipolar disorder, p self showed stronger and more pervasive genetic 41 correlations with facets of socioeconomic disadvantage (educational attainment, income, and 42 neighborhood deprivation), whereas p clinician was more strongly associated with medical disorders 43 unrelated to the brain. Genetic variance in p clinician that was unrelated to general vulnerability to 44 psychiatric symptoms was associated with less socioeconomic disadvantage, suggesting positive 45 selection biases in clinical samples used in psychiatric GWAS. These findings inform criticisms 46 of psychiatric nosology by suggesting that cross-disorder genetic liabilities identified in GWASs 47 of clinician-defined psychiatric disease are relatively distinct from genetic liabilities operating on 48 self-reported symptom variation in the general population. 49