PF and SLE are employees of 23andMe, Inc., and hold stock or stock options in 23andMe. Our results further delineate the role of CADM2 in impulsivity and numerous other psychiatric and somatic traits across ancestries and species. Our MouseWAS recapitulated some of the associations found in humans, including impulsivity, cognition, and BMI. PheWAS for CADM2 variants identified associations with 378 traits in European participants, and 47 traits in Latin American participants, replicating associations with risky behaviors, cognition and BMI, and revealing novel associations including allergies, anxiety, irritable bowel syndrome, and migraine. We identified significant associations proximal to genes such as TCF4 and PTPRF, and also identified nominal associations proximal to DRD2 and CRHR1. In humans, impulsive personality traits showed modest chip-heritability (∼6-11%), and moderate genetic correlations ( r g=.20-.50) with other personality traits, and various psychiatric and medical traits.
Finally, we produced Cadm2 mutant mice and used them to perform a Mouse-PheWAS (“MouseWAS”) by testing them with a battery of relevant behavioral tasks.
Because these GWAS implicated the gene CADM2, we next performed single-SNP phenome-wide studies ( PheWAS) of several of the implicated variants in CADM2 in a multi-ancestral 23andMe cohort (N=3,229,317, European N=579,623, Latin American N=199,663, African American).
We performed genome-wide association studies ( GWAS) of eight impulsive personality traits from the Barratt Impulsiveness Scale and the short UPPS-P Impulsive Personality Scale (N=123,509-133,517 23andMe research participants of European ancestry), and a measure of Drug Experimentation (N=130,684). Impulsivity is a multidimensional heritable phenotype that broadly refers to the tendency to act prematurely and is associated with multiple forms of psychopathology, including substance use disorders.
0 kommentar(er)
