A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
Genome-Wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length (2020)


Li, C., Stoma, S., Lotta, L. A., Warner, S., Albrecht, E., Allione, A., Arp, P. P., Broer, L., Buxton, J. L., Da Silva Couto Alves, A., Deelen, J., Fedko, I. O., Gordon, S. D., Jiang, T., Karlsson, R., Kerrison, N., Loe, T. K., Mangino, M., Milaneschi, Y., . . . Codd, V. (2020). Genome-Wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length. American Journal of Human Genetics, 106(3), 389-404. https://doi.org/10.1016/j.ajhg.2020.02.006


JYU-tekijät tai -toimittajat


Julkaisun tiedot

Julkaisun kaikki tekijät tai toimittajat: 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.

Lehti tai sarja: American Journal of Human Genetics

ISSN: 0002-9297

eISSN: 1537-6605

Julkaisuvuosi: 2020

Volyymi: 106

Lehden numero: 3

Artikkelin sivunumerot: 389-404

Kustantaja: Cell Press

Julkaisumaa: Yhdysvallat (USA)

Julkaisun kieli: englanti

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

Julkaisun avoin saatavuus: Avoimesti saatavilla

Julkaisukanavan avoin saatavuus: Osittain avoin julkaisukanava

Julkaisu on rinnakkaistallennettu (JYX): https://jyx.jyu.fi/handle/123456789/68058


Tiivistelmä

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.


YSO-asiasanat: telomeerit; ikääntyminen; genomiikka; meta-analyysi

Vapaat asiasanat: telomere length; biological aging; Mendelian randomisation; age-related disease


Liittyvät organisaatiot


OKM-raportointi: Kyllä

Raportointivuosi: 2020

JUFO-taso: 3


Viimeisin päivitys 2022-20-09 klo 13:11