Identification of genetic heterogeneity of Alzheimer's disease across age.

Published on Dec 1, 2019in Neurobiology of Aging4.347
· DOI :10.1016/J.NEUROBIOLAGING.2019.02.022
Min-Tzu Lo14
Estimated H-index: 14
(UCSD: University of California, San Diego),
Karolina Kauppi17
Estimated H-index: 17
(UCSD: University of California, San Diego)
+ 7 AuthorsChi-Hua Chen34
Estimated H-index: 34
(UCSD: University of California, San Diego)
Sources
Abstract
Abstract The risk of APOE for Alzheimer's disease (AD) is modified by age. Beyond APOE, the polygenic architecture may also be heterogeneous across age. We aim to investigate age-related genetic heterogeneity of AD and identify genomic loci with differential effects across age. Stratified gene-based genome-wide association studies and polygenic variation analyses were performed in the younger (60–79 years, N = 14,895) and older (≥80 years, N = 6559) age-at-onset groups using Alzheimer's Disease Genetics Consortium data. We showed a moderate genetic correlation (rg = 0.64) between the two age groups, supporting genetic heterogeneity. Heritability explained by variants on chromosome 19 (harboring APOE) was significantly larger in younger than in older onset group (p
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