Abstract:A recent genome-wide association study has identified an association between leukocyte telomere length (LTL) and a locus at 3q26 that includes TERC. In order to evaluate the effects of the SNPs rs12696304 and rs16847897 near TERC in the population of mainland China, we conducted an association study of LTL focusing on these two candidate SNPs in a sample of 4016 Chinese Han individuals. Multiple linear regression analyses were performed to evaluate the association of LTL with each SNP adjusted for age, gender … Show more
“…Prescott et al replicated previously identified GWAS loci TERC in the Nurses' Health Study but failed to replicate other locus or identify any new loci significant associated with Telomere Length . Shen et al, not surprisingly detected the TERC locus to have significant effect on Leukocyte Telomere Length in Chinese population through unbiased genome screening (Shen et al, 2011); the same two SNPs were found to be associated with Telomere Length as well as longevity in the oldest-old Danes (Soerensen et al, 2011).…”
Section: Telomere Length In the Genomic Eramentioning
“…Prescott et al replicated previously identified GWAS loci TERC in the Nurses' Health Study but failed to replicate other locus or identify any new loci significant associated with Telomere Length . Shen et al, not surprisingly detected the TERC locus to have significant effect on Leukocyte Telomere Length in Chinese population through unbiased genome screening (Shen et al, 2011); the same two SNPs were found to be associated with Telomere Length as well as longevity in the oldest-old Danes (Soerensen et al, 2011).…”
Section: Telomere Length In the Genomic Eramentioning
“…In the first instance, the significance threshold was determined by the Bonferroni method, which corrects the critical significance level by the number of tests (n) performed (a¼0.05/n), and is commonly used in candidate gene studies. 41 It is recognized that the Bonferroni correction can be overly conservative for non-independent tests. 42 Therefore, we calculated the number of independent tests performed.…”
Genetic influences have an important role in the ageing process. The genetic factors that influence success in bodily ageing may also contribute to the successful ageing of cognitive abilities. A comparative genomics approach found longevity genes conserved between yeast Saccharomyces cerevisiae and nematode Caenorhabditis elegans. We hypothesised that these longevity genes influence variance in cognitive ability and age-related cognitive decline in humans. Here, we investigated six of these genes that have human orthologs and show expression in the brain. We tested AFG3L2 (MIM: 604581, AFG3 ATPase family gene 3-like 2 (yeast)), FRAP1 (MIM: 601231, a FK506 binding protein 12-rapamycin associated protein), MAT1A, MAT2A (MIM: 610550 and 601468, methionine adenosyltransferases I alpha and II alpha, respectively), SYNJ1 and SYNJ2 (MIM: 604297 and 609410, synaptojanin-1 and synaptojanin-2, respectively) in approximately 1000 healthy older Scots: the Lothian Birth Cohort 1936 (LBC1936). They were tested on general cognitive ability at age 11 years. At a mean age of 70 years, they re-sat the same general cognitive ability test and underwent an additional battery of diverse cognitive tests. In all, 70 tag and functional SNPs in the six longevity genes were genotyped and tested for association with cognition and cognitive ageing in LBC1936. Suggestive associations were detected between SNPs in SYNJ2, MAT1A, AFG3L2 and SYNJ1 and a general memory factor and general cognitive ability at age 11 and 70 years. Replication studies for cognitive ability associations were performed in 2506 samples from the Cognitive Ageing Genetics in England and Scotland consortium. A meta-analysis replicated the SYNJ2 association with cognitive abilities (lowest P¼0.00077). SYNJ2 is a novel gene in which variation is potentially associated with cognitive abilities.
“…11 Genetic association studies have revealed associations between single-nucleotide polymorphisms (SNPs) in the TERC and TERT genes and TL. [11][12][13][14][15][16][17] Other studies reported associations between SNPs in TERC and POT1 with human longevity, 11,17,18 suggesting that genes regulating TL may influence human longevity.…”
Telomere length (TL) has been associated with aging and mortality, but individual differences are also influenced by genetic factors, with previous studies reporting heritability estimates ranging from 34 to 82%. Here we investigate the heritability, mode of inheritance and the influence of parental age at birth on TL in six large, independent cohort studies with a total of 19 713 participants. The meta-analysis estimate of TL heritability was 0.70 (95% CI 0.64-0.76) and is based on a pattern of results that is highly similar for twins and other family members. We observed a stronger mother-offspring (r ¼ 0.42; P-value ¼ 3.60 Â 10 À61 ) than father-offspring correlation (r ¼ 0.33; P-value ¼ 7.01 Â 10 À5 ), and a significant positive association with paternal age at offspring birth (b ¼ 0.005; P-value ¼ 7.01 Â 10 À5 ). Interestingly, a significant and quite substantial correlation in TL between spouses (r ¼ 0.25; P-value ¼ 2.82 Â 10 À30 ) was seen, which appeared stronger in older spouse pairs (mean age Z55 years; r ¼ 0.31; P-value ¼ 4.27 Â 10 À23 ) than in younger pairs (mean ageo55 years; r ¼ 0.20; P-value ¼ 3.24 Â 10 À10 ). In summary, we find a high and very consistent heritability estimate for TL, evidence for a maternal inheritance component and a positive association with paternal age. European Journal of Human Genetics (2013) 21, 1163-1168; doi:10.1038/ejhg.2012.303; published online 16 January 2013Keywords: telomere length; heritability; paternal age effect
INTRODUCTIONTelomeres are specialized DNA structures located at the terminal ends of chromosomes. 1 Their primary function is to maintain genomic stability. Because of the inability of DNA polymerase to fully replicate the 3 0 end of the DNA strand, that is, the 'end-replication problem' , telomeres naturally shorten with each cell division and, therefore, with age. [2][3][4] In epidemiological studies, both of cross-sectional and prospective design, decreased telomere length (TL) in leukocytes was associated with increased mortality, 5-8 although this finding was not consistent. 9,10 Increased TL in leukocytes has been associated with longevity in a comparison of long-lived Ashkenazi Jews and their offspring with younger controls. 11 Genetic association studies have revealed associations between single-nucleotide polymorphisms (SNPs) in the TERC and TERT genes and TL. [11][12][13][14][15][16][17] Other studies reported associations between SNPs in TERC and POT1 with human longevity, 11,17,18 suggesting that genes regulating TL may influence human longevity.
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