https://scholars.lib.ntu.edu.tw/handle/123456789/412786
標題: | Identification of genetic heterogeneity of Alzheimer's disease across age | 作者: | Lo, Min-Tzu Kauppi, Karolina Fan, Chun-Chieh Sanyal, Nilotpal Reas, Emilie T Sundar, V S WEN-CHUNG LEE Desikan, Rahul S McEvoy, Linda K Chen, Chi-Hua |
關鍵字: | Alzheimer's disease; Gene-based analysis; Genetic correlation; Genetic heterogeneity; Stratified GWAS | 公開日期: | 12-三月-2019 | 來源出版物: | Neurobiology of aging | 摘要: | 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 < 0.05). APOE region, BIN1, OR2S2, MS4A4E, and PICALM were identified at the gene-based genome-wide significance (p < 2.73 × 10-6) with larger effects at younger age (except MS4A4E). For the novel gene OR2S2, we further performed leave-one-out analyses, which showed consistent effects across subsamples. Our results suggest using genetically more homogeneous individuals may help detect additional susceptible loci. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/412786 | ISSN: | 01974580 | DOI: | https://api.elsevier.com/content/abstract/scopus_id/85064014761 10.1016/j.neurobiolaging.2019.02.022 |
SDG/關鍵字: | apolipoprotein E; BIN1 protein; brain protein; MS4A4E protein; OR2S2 protein; PICALM protein; unclassified drug; adult; age; age distribution; aged; Alzheimer disease; Article; chromosome 19; controlled study; gene; gene locus; genetic correlation; genetic heterogeneity; genetic variation; genome-wide association study; human; major clinical study; onset age; OR2S2 gene; priority journal; single nucleotide polymorphism; Alzheimer disease; genetics; Alzheimer Disease; Genetic Heterogeneity; Humans |
顯示於: | 流行病學與預防醫學研究所 |
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