Polygenic basis and biomedical consequences of telomere length variation,Nature Genetics

当前位置： X-MOL 学术 › Nat. Genet. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Polygenic basis and biomedical consequences of telomere length variation
Nature Genetics ( IF 30.8 ) Pub Date : 2021-10-05 , DOI: 10.1038/s41588-021-00944-6
Veryan Codd _{1,

2} , Qingning Wang _{1,

2} , Elias Allara _{3,

4} , Crispin Musicha _{1,

2} , Stephen Kaptoge _{3,

4,

5} , Svetlana Stoma ₁ , Tao Jiang ₃ , Stephen E Hamby _{1,

2} , Peter S Braund ₁ , Vasiliki Bountziouka _{1,

2} , Charley A Budgeon _{1,

2,

6} , Matthew Denniff ₁ , Chloe Swinfield ₁ , Manolo Papakonstantinou ₁ , Shilpi Sheth ₁ , Dominika E Nanus ₁ , Sophie C Warner ₁ , Minxian Wang _{7,

8} , Amit V Khera _{7,

8,

9,

10} , James Eales ₁₁ , Willem H Ouwehand _{5,

12,

13,

14} , John R Thompson ₁₅ , Emanuele Di Angelantonio _{3,

4,

5,

16} , Angela M Wood _{3,

4,

5,

16,

17} , Adam S Butterworth _{3,

4,

5,

16} , John N Danesh _{3,

4,

5,

16,

18} , Christopher P Nelson _{1,

2} , Nilesh J Samani _{1,

2}

Affiliation

Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK.
British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, UK.
British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK.
School of Population and Global Health, University of Western Australia, Perth, Western Australia, Australia.
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Department of Medicine, Harvard Medical School, Boston, MA, USA.
Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Division of Cardiovascular Sciences, University of Manchester, Manchester, UK.
Department of Haematology, University of Cambridge, Cambridge, UK.
NHS Blood and Transplant, Cambridge, UK.
University College London Hospitals NHS Foundation Trust, London, UK.
Department of Health Sciences, University of Leicester, Leicester, UK.
Health Data Research UK Cambridge, Wellcome Sanger Institute, EMBL-European Bioinformatics Institute and University of Cambridge, Cambridge, UK.
The Alan Turing Institute, London, UK.
Department of Human Genetics, Wellcome Sanger Institute, Hinxton, UK.

Telomeres, the end fragments of chromosomes, play key roles in cellular proliferation and senescence. Here we characterize the genetic architecture of naturally occurring variation in leukocyte telomere length (LTL) and identify causal links between LTL and biomedical phenotypes in 472,174 well-characterized UK Biobank participants. We identified 197 independent sentinel variants associated with LTL at 138 genomic loci (108 new). Genetically determined differences in LTL were associated with multiple biological traits, ranging from height to bone marrow function, as well as several diseases spanning neoplastic, vascular and inflammatory pathologies. Finally, we estimated that, at the age of 40 years, people with an LTL >1 s.d. shorter than the population mean had a 2.5-year-lower life expectancy compared with the group with ≥1 s.d. longer LDL. Overall, we furnish new insights into the genetic regulation of LTL, reveal wide-ranging influences of LTL on physiological traits, diseases and longevity, and provide a powerful resource available to the global research community.

中文翻译：

端粒长度变异的多基因基础和生物医学后果

端粒是染色体的末端片段，在细胞增殖和衰老中起着关键作用。在这里，我们描述了白细胞端粒长度 (LTL) 自然发生变异的遗传结构，并在 472,174 名具有良好特征的英国生物银行参与者中确定了 LTL 与生物医学表型之间的因果关系。我们在 138 个基因组位点（108 个新位点）鉴定了 197 个与 LTL 相关的独立哨兵变异。基因决定的 LTL 差异与多种生物学特征相关，从身高到骨髓功能，以及跨越肿瘤、血管和炎症病理学的多种疾病。最后，我们估计，在 40 岁时，LTL 比人口平均值短 >1 sd 的人与 LDL 长 ≥ 1 sd 的人群相比，预期寿命低 2.5 年。

更新日期：2021-10-05

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南

全部期刊列表>>