@article{e43d3fe5e8dc4003aaf6815c564042e8,
title = "Polygenic basis and biomedical consequences of telomere length variation",
abstract = "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.",
author = "Veryan Codd and Qingning Wang and Elias Allara and Crispin Musicha and Stephen Kaptoge and Svetlana Stoma and Tao Jiang and Hamby, {Stephen E} and Braund, {Peter S} and Vasiliki Bountziouka and Budgeon, {Charley A} and Matthew Denniff and Chloe Swinfield and Manolo Papakonstantinou and Shilpi Sheth and Nanus, {Dominika E} and Warner, {Sophie C} and Minxian Wang and Khera, {Amit V} and James Eales and Ouwehand, {Willem H} and {Di Angelantonio}, Emanuele and Wood, {Angela M} and Butterworth, {Adam S} and Danesh, {John N} and Samani, {Nilesh J}",
note = "Funding Information: This research has been conducted using the UKB Resource under application number 6077 and was funded by the UK Medical Research Council (MRC), Biotechnology and Biological Sciences Research Council and British Heart Foundation (BHF) through MRC grant no. MR/M012816/1. The authors are also supported by grants from the BHF (grant nos. SP/16/4/32697 (C.P.N.); RG/13/13/30194, RG/18/13/33946 and CH/12/2/29428 (E.A., S.K., T.J., E.D.A., A.M.W., A.S.B. and J.N.D.)), MRC (grant no. MR/L003120/1 (E.A., S.K., T.J., E.D.A., A.M.W., A.S.B. and J.N.D.)), the National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Centre (grant no. BRC-1215-20010 (V.C., C.A.B., C.M., V.B., Q.W., S.E.H., C.P.N. and N.J.S.)), NIHR Cambridge Biomedical Research Centre (grant no. BRC-1215-20014 (E.A., S.K., T.J., E.D.A., A.M.W., A.S.B. and J.N.D.)), NIHR Blood and Transplant Research Unit in Donor Health and Genomics (grant no. NIHR BTRU-2014-10024 (E.A., S.K., T.J., E.D.A., A.M.W., A.S.B. and J.N.D.)), Health Data Research UK (E.A., S.K., T.J., E.D.A., A.M.W., A.S.B. and J.N.D.) and EU/EFPIA Innovative Medicines Initiative Joint Undertaking BigData@Heart (grant no. 11607 (A.M.W. and E.A)). J.N.D. holds a BHF Personal Professorship, and J.N.D. and W.H.O. hold NIHR Senior Investigator Awards. V.C., Q.W. and C.P.N. acknowledge support from the University of Leicester van Geest Heart and Cardiovascular Diseases Research Fund. W.H.O. acknowledges support from the NIHR, MRC, NHS Blood and Transplant and Thermo Fisher Scientific. P. Akbari, T. Bolton and M. Arnold made computational and biostatistical contributions to this work. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = oct,
day = "5",
doi = "10.1038/s41588-021-00944-6",
language = "English",
volume = "53",
pages = "1425--1433",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Research",
number = "10",
}