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阿尔茨海默病多基因风险评分与脑震荡严重程度及恢复指标的关联

Association of Alzheimer's Disease Polygenic Risk Score with Concussion Severity and Recovery Metrics.

作者信息

Dybing Kaitlyn M, McAllister Thomas W, Wu Yu-Chien, McDonald Brenna C, Broglio Steven P, Mihalik Jason P, Guskiewicz Kevin M, Goldman Joshua T, Jackson Jonathan C, Saykin Andrew J, Risacher Shannon L, Nudelman Kelly N H

机构信息

Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA.

Indiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, IN, USA.

出版信息

Sports Med. 2025 Jan 16. doi: 10.1007/s40279-024-02150-w.

Abstract

BACKGROUND

Identification of genetic alleles associated with both Alzheimer's disease (AD) and concussion severity/recovery could help explain the association between concussion and elevated dementia risk. However, there has been little investigation into whether AD risk genes associate with concussion severity/recovery, and the limited findings are mixed.

OBJECTIVE

We used AD polygenic risk scores (PRS) and APOE genotypes to investigate any such associations in the NCAA-DoD Grand Alliance CARE Consortium (CARE) dataset.

METHODS

We assessed six concussion outcomes in 931 participants, including two recovery measures (number of days to asymptomatic and to return to play (RTP)) and four severity measures (scores on SAC and BESS, SCAT symptom severity and total number of symptoms). We calculated the PRS using a published score and performed multiple linear regression to assess the relationship of the PRS with outcomes. We also used ANOVAs, t-tests, and chi-square tests to examine outcomes by APOE genotype.

RESULTS

Higher PRS was associated with longer injury to RTP time in the normal RTP (< 24 days) subgroup (p = 0.024). A one standard deviation increase in the PRS resulted in a 9.89 hour increase to RTP time. This result was no longer significant after inclusion of covariates. There were no other consistently significant effects.

CONCLUSIONS

Our findings suggest high AD genetic risk is not associated with more severe concussions or poor recovery in young adults. Future studies should attempt to replicate these findings in larger samples with longer follow-up using PRS calculated from diverse populations.

摘要

背景

识别与阿尔茨海默病(AD)以及脑震荡严重程度/恢复情况相关的基因等位基因,有助于解释脑震荡与痴呆风险升高之间的关联。然而,关于AD风险基因是否与脑震荡严重程度/恢复情况相关的研究较少,且有限的研究结果并不一致。

目的

我们使用AD多基因风险评分(PRS)和APOE基因型,在NCAA-国防部大联盟CARE联盟(CARE)数据集中研究此类关联。

方法

我们评估了931名参与者的六种脑震荡结果,包括两种恢复指标(无症状天数和恢复比赛(RTP)天数)以及四种严重程度指标(SAC和BESS评分、SCAT症状严重程度及症状总数)。我们使用已发表的评分计算PRS,并进行多元线性回归以评估PRS与结果之间的关系。我们还使用方差分析、t检验和卡方检验,按APOE基因型检查结果。

结果

在正常RTP(<24天)亚组中,较高的PRS与更长的受伤至RTP时间相关(p = 0.024)。PRS每增加一个标准差,RTP时间增加9.89小时。纳入协变量后,该结果不再显著。没有其他一致的显著影响。

结论

我们的研究结果表明,高AD遗传风险与年轻人更严重的脑震荡或恢复不佳无关。未来的研究应尝试在更大样本、更长随访期内,使用来自不同人群计算的PRS来重复这些发现。

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