Genomic structural equation modeling of reward-related traits: exploring the genetic factor structure and its relationship with psychopathology.

Reward sensitivity has a partial genetic background, and extreme levels may increase vulnerability to psychopathology. This study explores the genetic factor structure underlying reward-related traits and examines how genetic variance links to psychopathology. We modeled GWAS data from ten reward-related traits: risk tolerance (N = 975,353), extraversion (N = 122,886), sensation seeking (N = 132,395), (lack of) premeditation (N = 132,667), (lack of) perseverance (N = 133,517), positive urgency (N = 132,132), negative urgency (N = 132,559), attentional impulsivity (N = 124,739), motor impulsivity (N = 124,104), and nonplanning impulsivity (N = 123,509) to derive their genetic factor structure. A GWAS on this structure was performed, and polygenic scores (PGS) were generated to test associations with problems related to attention, hyperactivity, autism, aggression, mood, anxiety, alcohol use, smoking, and drug use problems in up to 78,000 individuals from the Dutch Lifelines Study. A two-factor model fit best - "reward interest" (openness to rewards) and "impulsivity" (pursuit of rewards with little consideration of consequences). The reward interest PGS was positively associated with hyperactivity, alcohol, smoking, and drug use, and negatively with autism spectrum problems. The impulsivity PGS was positively associated with all studied psychopathology. These findings demonstrate the feasibility of using related traits to investigate the dimensionality of reward sensitivity and how distinct aspects may be linked to different psychopathology domains.