2019
DOI: 10.1093/brain/awy327
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Polygenic hazard score, amyloid deposition and Alzheimer’s neurodegeneration

Abstract: Mounting evidence indicates that the polygenic basis of late-onset Alzheimer's disease can be harnessed to identify individuals at greatest risk for cognitive decline. We have previously developed and validated a polygenic hazard score comprising of 31 single nucleotide polymorphisms for predicting Alzheimer's disease dementia age of onset. In this study, we examined whether polygenic hazard scores are associated with: (i) regional tracer uptake using amyloid PET; (ii) regional volume loss using longitudinal M… Show more

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Cited by 68 publications
(71 citation statements)
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References 38 publications
(48 reference statements)
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“…Some researchers have combined the effects of known variants into a polygenic hazard score. Such combined genetics scores have demonstrated better prediction of the age of onset for AD versus APOE status alone 15,17 and may correlate with amyloid beta and tau accumulation, and cortical volume changes 17 .…”
Section: Apoe Genotype and Other Genetic Risk Analysesmentioning
confidence: 99%
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“…Some researchers have combined the effects of known variants into a polygenic hazard score. Such combined genetics scores have demonstrated better prediction of the age of onset for AD versus APOE status alone 15,17 and may correlate with amyloid beta and tau accumulation, and cortical volume changes 17 .…”
Section: Apoe Genotype and Other Genetic Risk Analysesmentioning
confidence: 99%
“…Most existing models rely heavily on cognitive test results to drive their prediction and many have focused on the progression of individuals with MCI 26,27 . Predictions have been made using genetics alone 8 , MRI alone 9,28 , and through the combination of genetics with MRI and cognitive testing 10,15,17 .…”
Section: Prediction Models In the Literaturementioning
confidence: 99%
“… Abstract Sex differences in the manifestations of Alzheimer’s disease (AD) are under intense investigations 1,2 . Despite the emerging importance of polygenic predictions for AD 38 , the sex-dependent polygenic effects have not been demonstrated. Here, using a sex crossover analysis, we show that sex-dependent autosomal genetic effects on AD can be revealed by characterizing disease progress via the hazard function.…”
mentioning
confidence: 99%
“…This sex-agnostic status quo is particularly problematic for disease prediction based on polygenic effects. By aggregating the estimated regression weights of autosomal single-nucleotide-polymorphisms (SNPs) from genome-wide association studies (GWAS), polygenic scores have been used to assist in several important clinical functions, including disease prediction 20 , risk stratification 21 , enriching clinical trials 6,22 , and facilitating disease screening 23 . However, because the standard practice in GWAS treated sex as a confounding factor for autosomal effects, the basis of polygenic scores, the estimated odds ratios, are devoid of sex-dependent effects.…”
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confidence: 99%
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