作者
Veryan Codd,Qingning Wang,Elias Allara,Crispin Musicha,Stephen Kaptoge,Svetlana Stoma,Tao Jiang,Stephen E. Hamby,Peter S. Braund,Vasiliki Bountziouka,Charley Budgeon,Matthew Denniff,Chloe Swinfield,Manolo Papakonstantinou,Shilpi Sheth,Dominika E Nanus,Sophie C Warner,Minxian Wang,Amit V. Khera,James Eales,Willem H. Ouwehand,John R. Thompson,Emanuele Di Angelantonio,Angela Wood,Adam S. Butterworth,John Danesh,Christopher P. Nelson,Nilesh J. Samani
摘要
Telomeres, the end fragments of chromosomes, play key roles in cellular proliferation and senescence 1 . Here we characterize the genetic architecture of naturally-occurring variation in leucocyte telomere length (LTL) and identify causal links between LTL and biomedical phenotypes in 472,174 well-characterized participants in UK Biobank 2 . We identified 197 independent sentinel variants associated with LTL at 138 genomic loci (108 novel). 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 age 40 years, people with >1-SD shorter compared to ≥1-SD longer LTL than the population mean had 2.5 years lower life expectancy. Overall, we furnish novel insights into the genetic regulation of LTL, reveal LTL’s wide-ranging influences on physiological traits, diseases, and longevity, and provide a powerful resource available to the global research community.