Abstract
The genetic underpinnings of cognitive resilience in aging remains unknown. Predicting an individual’s rate of cognitive decline—or cognitive resilience—using genetics will allow personalized intervention for cognitive enhancement and optimal selection of target samples in clinical trials. Here, using genome-wide polygenic scores(GPS) of cognitive capacity as the genomic indicators for variations of human intelligence, we examined the genetic liability of cognitive abilities in the behavioral/cognitive phenome to understand individual phenotypic differences over time. We analyzed the 18-year records of the cross-sectional and longitudinal sociogenomic data of 8,511 European-ancestry adults from the Wisconsin Longitudinal Study (WLS), especially focusing on the cognitive assessments that were repeatedly administered to the participants at their average ages of 64.5 and 71.5. Our linear mixed-effects model identified a significant interaction effect between age and cognitive capacity GPS, which indicates that a higher cognitive capacity GPS significantly correlates with a slower cognitive decline in the domain of immediate memory recall (p-value = 1.79E-03, β = 1.86E-01). Also, the phenome-wide analysis identified several significant associations of cognitive capacity GPSs on the cognitive and behavioral phenome, such as Similarities task (p-value = 3.59E-74, β = 1.36, 95% CI=(1.22, 1.51)), Number Series task(p-value = 2.55E-78, β = 0.94, 95% CI=(0.85, 1.04)), IQ scores(p-value = 7.74E-179, β = 1.42, 95% CI=(1.32, 1.51)), high school class rank (p-value = 3.07E-101, β = 1.86, 95% CI=(1.69, 2.02), Openness from the BIG 5 personality factor(p-value = 2.19E-14, β = 0.57, 95% CI=(0.42, 0.71)), and social participation of reading books (p-value = 2.03E-21, β = 0.50, 95% CI=(0.40, 0.60)), attending cultural events, such as concerts, plays or museums (p-value = 2.06E-23, β = 0.60, 95% CI=(0.49, 0.72)), and watching TV (p-value = 4.16E-18, β=-0.48, 95% CI=(-0.59, -0.37)). As the first phenome-wide analysis of cognitive and behavioral phenotypes, this study presents the novel genetic protective effects of cognitive ability on the decline of memory recall in an aging population.