title: Absence of association of a single-nucleotide polymorphism in the TERT-CLPTM1L locus with age-related phenotypes in a large multicohort study: the HALCyon programme.
abstract: Several age-related traits are associated with shorter telomeres, the structures that cap the end of linear chromosomes. A common polymorphism near the telomere maintenance gene TERT has been associated with several cancers, but relationships with other aging traits such as physical capability have not been reported. As part of the Healthy Ageing across the Life Course (HALCyon) collaborative research programme, men and women aged between 44 and 90 years from nine UK cohorts were genotyped for the single-nucleotide polymorphism (SNP) rs401681. We then investigated relationships between the SNP and 30 age-related phenotypes, including cognitive and physical capability, blood lipid levels and lung function, pooling within-study genotypic effects in meta-analyses. No significant associations were found between the SNP and any of the cognitive performance tests (e.g. pooled beta per T allele for word recall z-score = 0.02, 95% CI: -0.01 to 0.04, P-value = 0.12, n = 18,737), physical performance tests (e.g. pooled beta for grip strength = -0.02, 95% CI: -0.045 to 0.006, P-value = 0.14, n = 11,711), blood pressure, lung function or blood test measures. Similarly, no differences in observations were found when considering follow-up measures of cognitive or physical performance after adjusting for its measure at an earlier assessment. The lack of associations between SNP rs401681 and a wide range of age-related phenotypes investigated in this large multicohort study suggests that while this SNP may be associated with cancer, it is not an important contributor to other markers of aging.
authors.affiliation: School of Social and Community Medicine, University of Bristol, UK. tamuno.alfred@bristol.ac.uk
authors.forename: Tamuno
authors.initials: T
authors.lastname: Alfred
authors.forename: Yoav
authors.initials: Y
authors.lastname: Ben-Shlomo
authors.forename: Rachel
authors.initials: R
authors.lastname: Cooper
authors.forename: Rebecca
authors.initials: R
authors.lastname: Hardy
authors.forename: Cyrus
authors.initials: C
authors.lastname: Cooper
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Deary
authors.forename: Jane
authors.initials: J
authors.lastname: Elliott
authors.forename: David
authors.initials: D
authors.lastname: Gunnell
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Harris
authors.forename: Mika
authors.initials: M
authors.lastname: Kivimaki
authors.forename: Meena
authors.initials: M
authors.lastname: Kumari
authors.forename: Richard M
authors.initials: RM
authors.lastname: Martin
authors.forename: Chris
authors.initials: C
authors.lastname: Power
authors.forename: Avan Aihie
authors.initials: AA
authors.lastname: Sayer
authors.forename: John M
authors.initials: JM
authors.lastname: Starr
authors.forename: Diana
authors.initials: D
authors.lastname: Kuh
authors.forename: Ian N M
authors.initials: IN
authors.lastname: Day
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D000886:Anthropometry; D001794:Blood Pressure; D003071:Cognition; D016172:DNA Fingerprinting / Q000379:methods; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D040361:Healthy People Programs; D006801:Humans; D008055:Lipids / Q000097:blood; D008137:Longitudinal Studies; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D010807:Physical Endurance; D020641:Polymorphism, Single Nucleotide; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism; D016615:Telomere; D006113:United Kingdom
chemical_list: C422445:CLPTM1L protein, human; D008055:Lipids; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C509186:TERT protein, human; D019098:Telomerase