Genome-wide Association Study of Creativity Reveals Genetic Overlap With Psychiatric Disorders, Risk Tolerance, and Risky Behaviors

Abstract

Creativity represents one of the most important and partially heritable human characteristics, yet little is known about its genetic basis. Epidemiological studies reveal associations between creativity and psychiatric disorders as well as multiple personality and behavioral traits. To test whether creativity and these disorders or traits share genetic basis, we performed genome-wide association studies (GWAS) followed by polygenic risk score (PRS) analyses. Two cohorts of Han Chinese subjects (4,834 individuals in total) aged 18-45 were recruited for creativity measurement using typical performance test. After exclusion of the outliers with significantly deviated creativity scores and low-quality genotyping results, 4,664 participants were proceeded for GWAS. We conducted PRS analyses using both the classical pruning and thresholding (P+T) method and the LDpred method. The extent of polygenic risk was estimated through linear regression adjusting for the top 3 genotyping principal components. R2 was used as a measurement of the explained variance. PRS analyses demonstrated significantly positive genetic overlap, respectively, between creativity with schizophrenia ((P+T) method: R2(max) ~ .196%, P = .00245; LDpred method: R2(max) ~ .226%, P = .00114), depression ((P+T) method: R2(max) ~ .178%, P = .00389; LDpred method: R2(max) ~ .093%, P = .03675), general risk tolerance ((P+T) method: R2(max) ~ .177%, P = .00399; LDpred method: R2(max) ~ .305%, P = .00016), and risky behaviors ((P+T) method: R2(max) ~ .187%, P = .00307; LDpred method: R2(max) ~ .155%, P = .00715). Our results suggest that human creativity is probably a polygenic trait affected by numerous variations with tiny effects. Genetic variations that predispose to psychiatric disorders and risky behaviors may underlie part of the genetic basis of creativity, confirming the epidemiological associations between creativity and these traits.