当前位置: 首页 > 详情页

Interpretation of 10 years of Alzheimer's disease genetic findings in the perspective of statistical heterogeneity

文献详情

资源类型:
WOS体系:
Pubmed体系:

收录情况: ◇ SCIE

机构: [1]Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, No. 10, Xitoutiao, You'an Men Wai, Fengtai District, Beijing 100069, China. [2]Chinese Institute for Brain Research, No. 26, Kexueyuan Road, Changping District, Beijing 102206, China. [3]State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, No. 5, Dongdan Santichao, Dongcheng District, Beijing 100193, China. [4]School of Computer Science and Technology, Harbin Institute of Technology, No. 92, Xidazhi Street, Nangang District, Harbin 150006, China. [5]School of Biomedical Engineering, Capital Medical University, No. 10 Xitoutiao, You'an Men Wai, Fengtai District, Beijing 100069, China. [6]Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida WaiLong, Taipa 999078, Macao SAR, China. [7]Department of Epidemiology and Biostatistics, School of Public Health, Wannan Medical College, No. 22, Wenchang Road, Wuhu 241002, Anhui, China. [8]Institute of Chronic Disease Prevention and Control, Wannan Medical College, No. 22, Wenchang Road, Wuhu 241002, Anhui, China. [9]Key Laboratory of Cerebral Microcirculation in Universities of Shandong, Department of Neurology, Second Affiliated Hospital, Shandong First Medical University and Shandong Academy of Medical Sciences, Taian 271000, Shandong, China. [10]Beijing Key Laboratory of Hypoxia Translational Medicine, National Engineering Laboratory of Internet Medical Diagnosis and Treatment Technology, Xuanwu Hospital, Capital Medical University, No. 45, Changchun Road, Xicheng District, Beijing 100053, China.
出处:
ISSN:

关键词: Alzheimer’s disease genome-wide association studies GWAS by proxy statistical heterogeneity phenotypic heterogeneity

摘要:
Common genetic variants and susceptibility loci associated with Alzheimer's disease (AD) have been discovered through large-scale genome-wide association studies (GWAS), GWAS by proxy (GWAX) and meta-analysis of GWAS and GWAX (GWAS+GWAX). However, due to the very low repeatability of AD susceptibility loci and the low heritability of AD, these AD genetic findings have been questioned. We summarize AD genetic findings from the past 10 years and provide a new interpretation of these findings in the context of statistical heterogeneity. We discovered that only 17% of AD risk loci demonstrated reproducibility with a genome-wide significance of P < 5.00E-08 across all AD GWAS and GWAS+GWAX datasets. We highlighted that the AD GWAS+GWAX with the largest sample size failed to identify the most significant signals, the maximum number of genome-wide significant genetic variants or maximum heritability. Additionally, we identified widespread statistical heterogeneity in AD GWAS+GWAX datasets, but not in AD GWAS datasets. We consider that statistical heterogeneity may have attenuated the statistical power in AD GWAS+GWAX and may contribute to explaining the low repeatability (17%) of genome-wide significant AD susceptibility loci and the decreased AD heritability (40-2%) as the sample size increased. Importantly, evidence supports the idea that a decrease in statistical heterogeneity facilitates the identification of genome-wide significant genetic loci and contributes to an increase in AD heritability. Collectively, current AD GWAX and GWAS+GWAX findings should be meticulously assessed and warrant additional investigation, and AD GWAS+GWAX should employ multiple meta-analysis methods, such as random-effects inverse variance-weighted meta-analysis, which is designed specifically for statistical heterogeneity.© The Author(s) 2024. Published by Oxford University Press.

基金:
语种:
被引次数:
WOS:
PubmedID:
中科院(CAS)分区:
出版当年[2023]版:
大类 | 2 区 生物学
小类 | 1 区 生化研究方法 1 区 数学与计算生物学
最新[2023]版:
大类 | 2 区 生物学
小类 | 1 区 生化研究方法 1 区 数学与计算生物学
JCR分区:
出版当年[2022]版:
Q1 BIOCHEMICAL RESEARCH METHODS Q1 MATHEMATICAL & COMPUTATIONAL BIOLOGY
最新[2023]版:
Q1 MATHEMATICAL & COMPUTATIONAL BIOLOGY Q1 BIOCHEMICAL RESEARCH METHODS

影响因子: 最新[2023版] 最新五年平均 出版当年[2022版] 出版当年五年平均 出版前一年[2021版] 出版后一年[2023版]

第一作者:
第一作者机构: [1]Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, No. 10, Xitoutiao, You'an Men Wai, Fengtai District, Beijing 100069, China.
共同第一作者:
通讯作者:
推荐引用方式(GB/T 7714):
APA:
MLA:

资源点击量:16409 今日访问量:0 总访问量:869 更新日期:2025-01-01 建议使用谷歌、火狐浏览器 常见问题

版权所有©2020 首都医科大学宣武医院 技术支持:重庆聚合科技有限公司 地址:北京市西城区长椿街45号宣武医院