Polygenic indices for cognition in healthy aging; the role of brain measures

Q4 Neuroscience Neuroimage. Reports Pub Date : 2023-03-01 DOI:10.1016/j.ynirp.2022.100153

A. Tsapanou , N. Mourtzi , Y. Gu , C. Habeck , D. Belsky , Y. Stern

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引用次数: 1

Abstract

Background

Genome-wide association studies (GWAS) have identified large numbers of genetic variants associated with cognition. However, little is known about how these genetic discoveries impact cognitive aging.

Methods

We conducted polygenic-index (PGI) analysis of cognitive performance in n = 168 European-ancestry adults aged 20–80. We computed PGIs based on GWAS of cognitive performance in young/middle-aged and older adults. We tested associations of the PGI with cognitive performance, as measured through neuropsychological evaluation. We explored whether these associations were accounted for by magnetic resonance imaging (MRI) measures of brain-aging phenotypes: total gray matter volume (GM), cortical thickness (CT), and white matter hyperintensities burden (WMH).

Results

Participants with higher PGI values performed better on cognitive tests (B = 0.627, SE = 0.196, p = 0.002) (age, sex, and principal components as covariates). Associations remained significant with inclusion of covariates for MRI measures of brain aging; B = 0.439, SE: 0.198, p = 0.028). PGI associations were stronger in young and middle-aged (age<65) as compared to older adults. For further validation, linear regression for Cog PGI and cognition in the fully adjusted model and adding the interaction between age group and Cog PGI, showed significant results (B = 0.892, SE: 0.325, p = 0.007) driven by young and middle-aged adults (B = −0.403, SE: 0.193, p = 0.039). In ancillary analysis, the Cognitive PGI was not associated with any of the brain measures.

Conclusions

Genetics discovered in GWAS of cognition are associated with cognitive performance in healthy adults across age, but most strongly in young and middle-aged adults. Associations were not explained by brain-structural markers of brain aging. Genetics uncovered in GWAS of cognitive performance may contribute to individual differences established relatively early in life and may not reflect genetic mechanisms of cognitive aging.

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健康老龄化认知的多基因指标；大脑测量的作用

背景全基因组关联研究（GWAS）已经发现了大量与认知相关的遗传变异。然而，人们对这些基因发现如何影响认知衰老知之甚少。方法我们对168名20-80岁的欧洲血统成年人的认知表现进行了多基因指数（PGI）分析。我们根据年轻人/中年人和老年人认知表现的GWAS计算PGI。我们通过神经心理学评估测试了PGI和认知表现的相关性。我们探讨了这些关联是否可以通过脑老化表型的磁共振成像（MRI）测量来解释：总灰质体积（GM）、皮层厚度（CT），结果PGI值较高的参与者在认知测试中表现较好（B=0.627，SE=0.196，p=0.002）（年龄、性别和主要成分为协变量）。纳入脑老化MRI测量的协变量后，相关性仍然显著；B=0.439，SE:0.198，p=0.028）。与老年人相比，年轻人和中年人（年龄＜65岁）的PGI相关性更强。为了进一步验证，在完全调整的模型中，Cog PGI和认知的线性回归，并添加年龄组和Cog PGI之间的相互作用，显示出由年轻人和中年人驱动的显著结果（B=-0.492，SE：0.325，p=0.007）（B=−0.403，SE：0.193，p=0.039）。在辅助分析中，认知PGI与任何大脑测量无关。结论GWAS中发现的认知遗传学与不同年龄段健康成年人的认知表现有关，但在中青年人中最为明显。大脑衰老的大脑结构标志物并不能解释这种联系。认知表现的GWAS中发现的遗传学可能有助于在生命早期建立的个体差异，并且可能不能反映认知衰老的遗传机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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