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Olle Melander

Principal investigator

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Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length

Author

  • Chen Li
  • Markus Perola
  • Paul Franks
  • Johan Gunnar Eriksson
  • Olle Melander
  • Peter Nilsson
  • Veryan Codd

Summary, in English

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.

Department/s

  • Genetic and Molecular Epidemiology
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health
  • Cardiovascular Research - Hypertension

Publishing year

2020

Language

English

Pages

389-404

Publication/Series

American Journal of Human Genetics

Volume

106

Issue

3

Document type

Journal article

Publisher

Cell Press

Topic

  • Medical Genetics

Keywords

  • age-related disease
  • biological aging
  • Mendelian randomisation
  • telomere length

Status

Published

Research group

  • Genetic and Molecular Epidemiology
  • Cardiovascular Research - Hypertension

ISBN/ISSN/Other

  • ISSN: 0002-9297