期刊
JOURNAL OF ALZHEIMERS DISEASE
卷 57, 期 1, 页码 275-283出版社
IOS PRESS
DOI: 10.3233/JAD-161070
关键词
Alzheimer's disease; apolipoprotein E; cognitive function; genetics; polygenic traits
资金
- Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6]
- Scottish Funding Council [HR03006]
- UK Medical Research Council (MRC)
- Wellcome Trust [104036/Z/14/Z]
- MRC
- BBSRC
- BBSRC [BB/F019394/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/F019394/1] Funding Source: researchfish
- Medical Research Council [1578661, MR/K026992/1, 1359901] Funding Source: researchfish
- Chief Scientist Office [CZD/16/6/4] Funding Source: researchfish
Stratification by genetic risk factors for Alzheimer's disease (AD) may help identify groups with the greatest disease risk. Biological changes that cause late-onset AD are likely to occur years, if not decades prior to diagnosis. Here, we select a subset of the Generation Scotland: Scottish Family Health Study cohort in a likely preclinical age-range of 60-70 years (subset n = 3,495 with cognitive and genetic data). We test for cognitive differences by polygenic risk scores for AD. The polygenic scores are constructed using all available SNPs, excluding those within a 500 kb distance of the APOE locus. Additive and multiplicative effects of APOE status on these associations are investigated. Small memory decrements were observed in those with high polygenic risk scores for AD (standardized beta -0.04, p = 0.020). These associations were independent of APOE status. There was no difference in AD polygenic scores across APOE haplotypes (p = 0.72). Individuals with high compared to low polygenic risk scores for AD (top and bottom 5% of the distribution) show cognitive decrements, albeit much smaller than for APOE epsilon 4 epsilon 4 compared to epsilon 3 epsilon 3 individuals (2.3 versus 3.5 fewer points on the processing speed test, and 1.8 versus 2.8 fewer points on the memory test). Polygenic risk scores for AD may help identify older individuals at greatest risk of cognitive decline and preclinical AD.
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