Shared genetic architecture between leukocyte telomere length and Alzheimer's disease.

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Tác giả: Zhi Cao, Qilong Tan, Chenjie Xu, Hongxi Yang

Ngôn ngữ: eng

Ký hiệu phân loại: 795.415 Contract bridge

Thông tin xuất bản: England : Alzheimer's research & therapy , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 746528

BACKGROUND: Epidemiological and clinical studies have reported an association between leukocyte telomere length (LTL) and Alzheimer's disease (AD). However, genetic association between the two phenotypes remains largely unknown. We aimed to elucidate the potential shared genetic architecture between LTL and AD. METHODS: Summary statistics from genome-wide association studies were obtained from large-scale biobank in European-ancestry populations for LTL (N = 472,174) and AD (71,880 cases, 383,378 controls). We examined the global and local genetic correlation between LTL and AD using linkage-disequilibrium score regression and ρ-HESS. We applied the bivariate causal mixture model (MiXeR) to calculate the number of shared genetic causal variants, and the conditional/conjunctional false discovery rate (condFDR/conjFDR) framework to identify specific shared loci between LTL and AD. Bidirectional two-sample Mendelian randomization (MR) were used to explore the causal associations between LTL and AD. RESULTS: We detected a significant genetic correlation between LTL and AD (r CONCLUSION: Our study identified specific shared loci between LTL and AD, providing new insights for polygenic overlap and molecular mechanisms, and highlighting new opportunities for future experimental validation.
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