期刊
NEUROBIOLOGY OF AGING
卷 123, 期 -, 页码 170-181出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2022.10.009
关键词
Alzheimer's disease; Growth factors; Targeted sequencing; EGF
This study aimed to investigate the role of rare and common variants of growth factors (GFs) in the genetic susceptibility of Alzheimer's disease (AD). The results showed an enrichment of rare missense variants in GF gene-set in AD patients, with the epidermal growth factor (EGF) being the most strongly associated. The common variant rs4698800 of EGF was significantly associated with AD risk, and increased EGF expression was observed in AD brain.
Alzheimer's disease (AD) is the most common neurodegenerative disease with high heritability. Growth factors (GFs) might contribute to the development of AD due to their broad effects on neuronal system. We herein aimed to investigate the role of rare and common variants of GFs in genetic susceptibility of AD. We screened 23 GFs in 6324 individuals using targeted sequencing. A rare-variant-based burden test and common-variant-based single-site association analyses were performed to identify AD-associated GF genes and variants. The burden test showed an enrichment of rare missense variants (p = 6.08 x 10(-4)) in GF gene-set in AD patients. Among the GFs, EGF showed the strongest signal of enrichment, especially for loss-of-function variants (p = 0.0019). A common variant rs4698800 of EGF showed significant associations with AD risk (p = 3.24 x 10(-5), OR = 1.26). The risk allele of rs4698800 was associated with an increased EGF expression, whereas EGF was indeed upregulated in AD brain. These findings suggested EGF as a novel risk gene for AD. (c) 2022 Elsevier Inc. All rights reserved.
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