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Common variants in SIRT1 and human longevity in a Chinese population.

ABSTRACT: The silent information regulator SIR2/SIRT1gene has been demonstrated as regulating lifespan in many model organisms, including yeast, worms, fruit flies and rodents. SIRT1, the human homolog of SIR2, is considered a candidate gene as a modifier of human life expectancy.In the current study we included 616 long-lived individuals and 846 matched younger controls to investigate associations between 8 common single nucleotide polymorphisms (SNPs) (i.e., rs12778366, rs3758391, rs3740051, rs33957861, rs7896005, rs12413112, rs11599176 and rs4746720) in the SIRT1 gene and human longevity.The 8 SNPs had strong linkage disequilibrium (LD) and were in an LD block, which was characterized by 4 common haplotypes that capture 99.3% of the genetic variation present within it. We found no evidence for statistically significant associations between the tested SIRT1 SNPs and longevity at the allele, genotype or haplotype levels.Current findings show that several common variants in SIRT1 are not associated with human longevity.

SUBMITTER: Lin R

PROVIDER: S-EPMC4836161 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Common variants in SIRT1 and human longevity in a Chinese population.

Lin Rong R Yan Dongjing D Zhang Yunxia Y Liao Xiaoping X Gong Gu G Hu Junjie J Fu Yunxin Y Cai Wangwei W

BMC medical genetics 20160418

<h4>Background</h4>The silent information regulator SIR2/SIRT1gene has been demonstrated as regulating lifespan in many model organisms, including yeast, worms, fruit flies and rodents. SIRT1, the human homolog of SIR2, is considered a candidate gene as a modifier of human life expectancy.<h4>Methods</h4>In the current study we included 616 long-lived individuals and 846 matched younger controls to investigate associations between 8 common single nucleotide polymorphisms (SNPs) (i.e., rs12778366 ...[more]

PMID: 27089876

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Project description:BackgroundPrevious studies have shown that individuals with schizophrenia have a greater risk for psoriasis than a typical person. This suggests that there might be a shared genetic etiology between the 2 conditions. We aimed to characterize the potential shared genetic susceptibility between schizophrenia and psoriasis using genome-wide marker genotype data.MethodsWe obtained genetic data on individuals with psoriasis, schizophrenia and control individuals. We applied a marker-based coheritability estimation procedure, polygenic score analysis, a gene set enrichment test and a least absolute shrinkage and selection operator regression model to estimate the potential shared genetic etiology between the 2 diseases. We validated the results in independent schizophrenia and psoriasis cohorts from Singapore.ResultsWe included 1139 individuals with psoriasis, 744 with schizophrenia and 1678 controls in our analysis, and we validated the results in independent cohorts, including 441 individuals with psoriasis (and 2420 controls) and 1630 with schizophrenia (and 1860 controls). We estimated that a large fraction of schizophrenia and psoriasis risk could be attributed to common variants (h2SNP = 29% ± 5.0%, p = 2.00 × 10-8), with a coheritability estimate between the traits of 21%. We identified 5 variants within the human leukocyte antigen (HLA) gene region, which were most likely to be associated with both diseases and collectively conferred a significant risk effect (odds ratio of highest risk quartile = 6.03, p < 2.00 × 10-16). We discovered that variants contributing most to the shared heritable component between psoriasis and schizophrenia were enriched in antigen processing and cell endoplasmic reticulum.LimitationsOur sample size was relatively small. The findings of 5 HLA gene variants were complicated by the complex structure in the HLA region.ConclusionWe found evidence for a shared genetic etiology between schizophrenia and psoriasis. The mechanism for this shared genetic basis likely involves immune and calcium signalling pathways.

Dataset Information

Common variants in SIRT1 and human longevity in a Chinese population.

Publications

Common variants in SIRT1 and human longevity in a Chinese population.

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