GWAS of Active Music Engagement Frequency in the Canadian Longitudinal Study on Aging

Active music engagement (AME), i.e., playing a musical instrument or singing, is moderately heritable and may support resilience to age-related functional decline. To understand AME's genetic architecture, we conducted a genome-wide association study (GWAS) in the Canadian Longitudinal Study on Aging (n = 23,782 with genetically inferred European ancestry). SNP-based heritability was estimated at 10%, revealing 21 independent loci at suggestive significance (p < 5×10^-5). Post-GWAS analyses showed enrichment in regulatory regions of adult brain cells and genetic correlations with musical rhythm ability, language, and cognition. Secondary genetic correlation analyses (bivariate-GREML) linked AME to enhanced cognition, motor function, social engagement, and resilience to psychological distress, but also increased mood disorder risk. Lastly, bi-directional Mendelian randomization indicated that individuals who have greater genetic propensity for musical rhythm abilities are more likely to have more frequent musical instrument or singing engagement. Overall, these findings suggest that the polygenic architecture of AME is enriched for neurobiological function, specifically promoter of astrocyte function, and shares genetic variation with healthy aging.