认知能力全基因组多基因评分可识别衰老过程中认知能力下降较慢的个体。
Cognitive Capacity Genome-Wide Polygenic Scores Identify Individuals with Slower Cognitive Decline in Aging.
机构信息
Division of Endocrinology, Metabolism, and Molecular Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Department of Psychology, College of Social Sciences, Seoul National University, Seoul 08825, Korea.
出版信息
Genes (Basel). 2022 Jul 24;13(8):1320. doi: 10.3390/genes13081320.
The genetic protective factors for cognitive decline in aging remain unknown. Predicting an individual's rate of cognitive decline-or with better cognitive resilience-using genetics will allow personalized intervention for cognitive enhancement and the 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 analyzed the 18-year records of cognitive and behavioral data of 8511 European-ancestry adults from the Wisconsin Longitudinal Study (WLS), specifically focusing on the cognitive assessments that were repeatedly administered to the participants with their average ages of 64.5 and 71.5. We identified a significant interaction effect between age and cognitive capacity GPS, which indicated that a higher cognitive capacity GPS significantly correlated with a slower cognitive decline in the domain of immediate memory recall (β = 1.86 × 10, -value = 1.79 × 10). The additional phenome-wide analyses identified several associations between cognitive capacity GPSs and cognitive/behavioral phenotypes, such as task (β = 1.36, 95% CI = (1.22, 1.51), -value = 3.59 × 10), task (β = 0.94, 95% CI = (0.85, 1.04), -value = 2.55 × 10), (β = 1.42, 95% CI = (1.32, 1.51), -value = 7.74 × 10), (β = 1.86, 95% CI = (1.69, 2.02), -value = 3.07 × 10), Openness from the BIG 5 personality factor (-value = 2.19 × 10, β = 0.57, 95% CI = (0.42, 0.71)), and leisure activity of reading books (β = 0.50, 95% CI = (0.40, 0.60), -value = 2.03 × 10), attending cultural events, such as concerts, plays, or museums (β = 0.60, 95% CI = (0.49, 0.72), -value = 2.06 × 10), and watching TV (β = -0.48, 95% CI = (-0.59, -0.37), -value = 4.16 × 10). 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.
衰老过程中认知能力下降的遗传保护因素尚不清楚。使用遗传学预测个体的认知下降速度——或者更好的认知弹性——可以为认知增强提供个性化干预，并在临床试验中为目标样本的最佳选择提供依据。在这里，我们使用认知能力的全基因组多基因评分 (GPS) 作为人类智力变化的基因组指标，分析了 8511 名欧洲血统成年人在威斯康星纵向研究 (WLS) 中的 18 年认知和行为数据记录，特别是关注那些反复接受参与者平均年龄为 64.5 岁和 71.5 岁的认知评估。我们发现年龄和认知能力 GPS 之间存在显著的交互效应，这表明较高的认知能力 GPS 与即时记忆回忆领域的认知衰退速度较慢显著相关（β=1.86×10，- 值=1.79×10）。额外的表型全基因组分析确定了认知能力 GPS 与认知/行为表型之间的几个关联，例如任务（β=1.36，95%CI=（1.22，1.51），- 值=3.59×10），任务（β=0.94，95%CI=（0.85，1.04），- 值=2.55×10），情景记忆（β=1.42，95%CI=（1.32，1.51），- 值=7.74×10），语义记忆（β=1.86，95%CI=（1.69，2.02），- 值=3.07×10），开放性的大五人格因素（- 值=2.19×10，β=0.57，95%CI=（0.42，0.71）），以及阅读书籍等休闲活动（β=0.50，95%CI=（0.40，0.60），- 值=2.03×10），参加文化活动，如音乐会、戏剧或博物馆（β=0.60，95%CI=（0.49，0.72），- 值=2.06×10），以及看电视（β=-0.48，95%CI=（-0.59，-0.37），- 值=4.16×10）。作为认知和行为表型的首次全表型分析，本研究提出了认知能力对记忆回忆下降的遗传保护作用的新发现，这种作用在老年人群中尤为明显。
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