Whole exome sequencing analyses reveal novel genes in telomere length and their biomedical implications

外显子组测序 生物 端粒 遗传学 外显子组 基因 等位基因 生命银行 表型 全基因组关联研究 基因型 单核苷酸多态性
作者
Weishi Liu,Bang‐Sheng Wu,Yang Liu,Shi-Dong Chen,Ya-Ru Zhang,Yue‐Ting Deng,Xinrui Wu,Xiao‐Yu He,Jing Yang,Jianfeng Feng,Wei Cheng,Yuming Xu,Jin‐Tai Yu
出处
期刊:GeroScience [Springer International Publishing]
卷期号:46 (5): 5365-5385
标识
DOI:10.1007/s11357-024-01203-2
摘要

Telomere length is a putative biomarker of aging and is associated with multiple age-related diseases. There are limited data on the landscape of rare genetic variations in telomere length. Here, we systematically characterize the rare variant associations with leukocyte telomere length (LTL) through exome-wide association study (ExWAS) among 390,231 individuals in the UK Biobank. We identified 18 robust rare-variant genes for LTL, most of which estimated effects on LTL were significant (> 0.2 standard deviation per allele). The biological functions of the rare-variant genes were associated with telomere maintenance and capping and several genes were specifically expressed in the testis. Three novel genes (ASXL1, CFAP58, and TET2) associated with LTL were identified. Phenotypic association analyses indicated significant associations of ASXL1 and TET2 with cancers, age-related diseases, blood assays, and cardiovascular traits. Survival analyses suggested that carriers of ASXL1 or TET2 variants were at increased risk for cancers; diseases of the circulatory, respiratory, and genitourinary systems; and all-cause and cause-specific deaths. The CFAP58 carriers were at elevated risk of deaths due to cancers. Collectively, the present whole exome sequencing study provides novel insights into the genetic landscape of LTL, identifying novel genes associated with LTL and their implications on human health and facilitating a better understanding of aging, thus pinpointing the genetic relevance of LTL with clonal hematopoiesis, biomedical traits, and health-related outcomes.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
刚刚
刚刚
2秒前
3秒前
香蕉觅云应助xuliangzheng采纳,获得10
3秒前
Hexagram发布了新的文献求助10
5秒前
yinggill完成签到 ,获得积分10
6秒前
帕丁顿发布了新的文献求助10
7秒前
7秒前
7秒前
真实的白翠完成签到,获得积分10
7秒前
汉堡包应助博士采纳,获得10
8秒前
温暖的沛凝完成签到 ,获得积分10
8秒前
醉熏的友卉完成签到,获得积分20
9秒前
万能图书馆应助夕夕口口采纳,获得10
9秒前
10秒前
10秒前
wenhao发布了新的文献求助10
11秒前
12秒前
jawa完成签到 ,获得积分10
12秒前
能干亦玉发布了新的文献求助10
12秒前
Orange应助guanghuawang采纳,获得10
13秒前
zhou完成签到,获得积分10
13秒前
kuoping完成签到,获得积分0
14秒前
15秒前
chen发布了新的文献求助10
15秒前
lelele发布了新的文献求助10
15秒前
科研通AI5应助Hexagram采纳,获得10
16秒前
16秒前
深情安青应助道松先生采纳,获得10
16秒前
KSDalton完成签到,获得积分10
16秒前
16秒前
tuanzi发布了新的文献求助10
17秒前
18秒前
pcr163应助仿生人采纳,获得100
19秒前
19秒前
xrL完成签到,获得积分10
19秒前
21秒前
HonamC完成签到,获得积分10
21秒前
星辰大海应助肯瑞恩哭哭采纳,获得10
21秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 700
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
Indomethacinのヒトにおける経皮吸収 400
Effective Learning and Mental Wellbeing 400
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3976058
求助须知:如何正确求助?哪些是违规求助? 3520294
关于积分的说明 11202245
捐赠科研通 3256804
什么是DOI,文献DOI怎么找? 1798471
邀请新用户注册赠送积分活动 877610
科研通“疑难数据库(出版商)”最低求助积分说明 806496