A1 Journal article (refereed)
Genome-Wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length (2020)


Li, Chen; Stoma, Svetlana; Lotta, Luca A.; Warner, Sophie; Albrecht, Eva; Allione, Alessandra; Arp, Pascal P.; Broer, Linda; Buxton, Jessica L.; Da Silva Couto Alves, Alexessander; Deelen, Joris et al. (2020). Genome-Wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length. American Journal of Human Genetics, 106 (3), 389-404. DOI: 10.1016/j.ajhg.2020.02.006


JYU authors or editors


Publication details

All authors or editors: Li, Chen; Stoma, Svetlana; Lotta, Luca A.; Warner, Sophie; Albrecht, Eva; Allione, Alessandra; Arp, Pascal P.; Broer, Linda; Buxton, Jessica L.; Da Silva Couto Alves, Alexessander; et al.

Journal or series: American Journal of Human Genetics

ISSN: 0002-9297

eISSN: 1537-6605

Publication year: 2020

Volume: 106

Issue number: 3

Pages range: 389-404

Publisher: Cell Press

Publication country: United States

Publication language: English

DOI: http://doi.org/10.1016/j.ajhg.2020.02.006

Open Access: Open access publication published in a hybrid channel

Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/68058


Abstract

Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1, PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.


Keywords: telomeres; ageing; genomics; meta-analysis

Free keywords: telomere length; biological aging; Mendelian randomisation; age-related disease


Contributing organizations


Ministry reporting: Yes

Reporting Year: 2020

Preliminary JUFO rating: 3


Last updated on 2020-18-08 at 13:33