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阿尔茨海默病的多基因风险评分与APOEε4阴性个体的痴呆风险相关。

Polygenic risk scores for Alzheimer's disease are related to dementia risk in APOE ɛ4 negatives.

作者信息

Najar Jenna, van der Lee Sven J, Joas Erik, Wetterberg Hanna, Hardy John, Guerreiro Rita, Bras Jose, Waern Margda, Kern Silke, Zetterberg Henrik, Blennow Kaj, Skoog Ingmar, Zettergren Anna

机构信息

Department of Psychiatry and Neurochemistry Neuropsychiatric Epidemiology Unit Institute of Neuroscience and Physiology the Sahlgrenska Academy Centre for Ageing and Health (AGECAP) at the University of Gothenburg Mölndal Sweden.

Region Västra Götaland Sahlgrenska University Hospital, Psychiatry, Cognition and Old Age Psychiatry Clinic Gothenburg Sweden.

出版信息

Alzheimers Dement (Amst). 2021 Jan 22;13(1):e12142. doi: 10.1002/dad2.12142. eCollection 2021.

Abstract

INTRODUCTION

Studies examining the effect of polygenic risk scores (PRS) for Alzheimer's disease (AD) and apolipoprotein E () genotype on incident dementia in very old individuals are lacking.

METHODS

A population-based sample of 2052 individuals ages 70 to 111, from Sweden, was followed in relation to dementia. AD-PRSs including 39, 57, 1333, and 13,942 single nucleotide polymorphisms (SNPs) were used.

RESULTS

AD-PRSs (including 39 or 57 SNPs) were associated with dementia (57-SNPs AD-PRS: hazard ratio 1.09, confidence interval 1.01-1.19, = .03), particularly in ɛ4 non-carriers (57-SNPs AD-PRS: 1.15, 1.05-1.27, 4 × 10, 39-SNPs AD-PRS: 1.22, 1.10-1.35, 2 × 10). No association was found with the other AD-PRSs. Further, ɛ4 was associated with increased risk of dementia (1.60, 1.35-1.92, = 1 × 10). In those aged ≥95 years, the results were similar for the AD-PRSs, while ɛ4 only predicted dementia in the low-risk tertile of AD-PRSs.

DISCUSSION

These results provide information to identify individuals at increased risk of dementia.

摘要

引言

目前缺乏关于阿尔茨海默病(AD)的多基因风险评分(PRS)和载脂蛋白E()基因型对高龄个体新发痴呆症影响的研究。

方法

对来自瑞典的2052名年龄在70至111岁之间的人群进行基于人群的痴呆症随访研究。使用了包含39、57、1333和13942个单核苷酸多态性(SNP)的AD-PRS。

结果

AD-PRS(包括39个或57个SNP)与痴呆症相关(57个SNP的AD-PRS:风险比1.09,置信区间1.01-1.19,=0.03),特别是在ɛ4非携带者中(57个SNP的AD-PRS:1.15,1.05-1.27,4×10,39个SNP的AD-PRS:1.22,1.10-1.35,2×10)。未发现与其他AD-PRS有相关性。此外,ɛ4与痴呆症风险增加相关(1.60,1.35-1.92,=1×10)。在年龄≥95岁的人群中,AD-PRS的结果相似,而ɛ4仅在AD-PRS的低风险三分位数中预测痴呆症。

讨论

这些结果为识别痴呆症风险增加的个体提供了信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1053/7821873/423a5e053d85/DAD2-13-e12142-g001.jpg

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