期刊
AMERICAN JOURNAL OF HUMAN GENETICS
卷 106, 期 3, 页码 389-404出版社
CELL PRESS
DOI: 10.1016/j.ajhg.2020.02.006
关键词
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资金
- European Union [HEALTH-F4-2007-201413]
- European Union (Integrated Project of the European Community) [LSHM-CT-2006-037197]
- UK Medical Research Council [MR/L003120/1]
- British Heart Foundation [RG/13/13/30194, RG/18/13/33946]
- European Commission Framework Programme 7 [HEALTH-F2-2012-279233]
- National Institute for Health Research (Cambridge Biomedical Research Centre at the Cambridge University Hospitals National Health Service (NHS) Foundation Trust)
- British Heart Foundation (BHF)
- National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Centre
- Wellcome Trust
- Medical Research Council [MC_UU_12015/1]
- NIHR
- MRC [MC_UU_12015/2, MC_UU_12015/1, MC_UU_00006/2, MR/L003120/1] Funding Source: UKRI
- NATIONAL CANCER INSTITUTE [ZIABC011815] Funding Source: NIH RePORTER
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.
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