| Autor: |
Min Qiao, Annie J. Lee, Dolly Reyes‐Dumeyer, Giuseppe Tosto, Kelley Faber, Alison Goate, Alan Renton, Michael Chao, Brad Boeve, Carlos Cruchaga, Margaret Pericak‐Vance, Jonathan L. Haines, Roger Rosenberg, Debby Tsuang, Robert A. Sweet, David A. Bennett, Robert S. Wilson, Tatiana Foroud, Richard Mayeux, Badri N. Vardarajan |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Annals of Clinical and Translational Neurology, Vol 10, Iss 5, Pp 744-756 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2328-9503 |
| DOI: |
10.1002/acn3.51757 |
| Popis: |
Abstract Objective To compute penetrance and recurrence risk using a genome‐wide PRS (including and excluding the APOE region) in families with Alzheimer's disease. Methods Genotypes from the National Institute on Aging Late‐Onset Alzheimer's Disease Family‐Based Study and a study of familial Alzheimer's disease in Caribbean Hispanics were used to compute PRS with and without variants in the 2 MB region flanking APOE. PRS was calculated in using clumping/thresholding and Bayesian methods and was assessed for association with Alzheimer's disease and age at onset. Penetrance and recurrence risk for carriers in highest and lowest PRS quintiles were compared separately within APOE‐ε4 carriers and non‐carriers. Results PRS excluding the APOE region was strongly associated with clinical and neuropathological diagnosis of AD. PRS association with AD was similar in participants who did not carry an APOE‐ε4 allele (OR = 1.74 [1.53–1.91]) compared with APOE‐ε4 carriers (1.53 [1.4–1.68]). Compared to the lowest quintile, the highest PRS quintile had a 10% higher penetrance at age 70 (p = 0.0006) and a 20% higher penetrance at age 80 (p |
| Databáze: |
Directory of Open Access Journals |
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