Single Nucleotide Polymorphisms Associated with Reading Ability Show Connection to Socio-Economic Outcomes.
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ABSTRACT:
SUBMITTER: Luciano M
PROVIDER: S-EPMC5574963 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Comparison of whole blood DNA methylation in 45 year-old humans with low and high childhood and adulthood socio-economic position Background: Disadvantaged socio-economic position (SEP) in childhood is associated with increased adult mortality and morbidity. We aimed to establish whether childhood SEP was associated with differential methylation of adult DNA. Methods: Forty adult males from the 1958 British Birth Cohort Study were selected from SEP extremes in both early childhood and mid-adulthood. We performed genome-wide methylation analysis on blood DNA taken at 45y using MeDIP (methylated DNA immunoprecipitation). We mapped in triplicate the methylation state of promoters of ~20,000 genes and 400 microRNAs. Probe methylation scores were averaged across triplicates and differential methylation between groups of individuals was determined. Differentially methylated promoter sites of selected genes were validated using pyrosequencing of bisulfite-converted DNA. Results: 9,112 variably methylated probes (from N=223,359 on the microarray) corresponded to 6,176 gene promoters with at least one variable probe. Unsupervised hierarchical clustering of probes obtained from the 500 most variable promoters revealed a cluster enriched with high SEP individuals confirming that SEP differences contribute to overall epigenetic variation. Methylation levels for 1252 gene promoters were associated with childhood SEP vs 545 promoters for adulthood SEP. Functionally, associations with childhood SEP appear in promoters of genes enriched in key cell signalling pathways. The differentially methylated promoters associated with SEP cluster in megabase-sized regions of the genome. Conclusions: Adult blood DNA methylation profiles show more associations with childhood SEP than adult SEP. Organization of these associations across the genome suggests a well-defined epigenetic pattern linked to early socio-economic environment.
2016-05-25 | GSE31713 | GEO
Project description:Human herpesvirus 8 (HHV-8) can be classified into distinct subtypes on the basis of sequence polymorphisms in several open reading frames (ORFs). We analyzed the subtypes of HHV-8 in 59 human immunodeficiency virus-infected Japanese patients by using polymorphisms in ORF26 and found that over two-thirds of the HHV-8 isolates fell into major subtype A. We also found that single nucleotide polymorphisms (SNPs) at nucleotide positions 1032 (C-to-A substitution) and 1055 (G-to-T substitution) in HHV-8 ORF26 were correlated with increased susceptibility to Kaposi's sarcoma, compared to the results obtained with HHV-8 with wild-type nucleotides at these positions (P = 0.0106). This observation suggests that molecular heterogeneity of the HHV-8 genome affects the biological properties of HHV-8, resulting in different clinical phenotypes of HHV-8 infection. Since sensitive PCR of ORF26 allowed us to analyze the SNPs by using peripheral blood from HHV-8-infected patients, the ORF26 SNPs will be a potent tool for investigating the pathogenesis of HHV-8 infection.
| S-EPMC156527 | biostudies-literature
Project description:Single-nucleotide polymorphisms (SNPs) provide an abundant source of DNA polymorphisms in a number of eukaryotic species. Information on the frequency, nature, and distribution of SNPs in plant genomes is limited. Thus, our objectives were (1) to determine SNP frequency in coding and noncoding soybean (Glycine max L. Merr.) DNA sequence amplified from genomic DNA using PCR primers designed to complete genes, cDNAs, and random genomic sequence; (2) to characterize haplotype variation in these sequences; and (3) to provide initial estimates of linkage disequilibrium (LD) in soybean. Approximately 28.7 kbp of coding sequence, 37.9 kbp of noncoding perigenic DNA, and 9.7 kbp of random noncoding genomic DNA were sequenced in each of 25 diverse soybean genotypes. Over the >76 kbp, mean nucleotide diversity expressed as Watterson's theta was 0.00097. Nucleotide diversity was 0.00053 and 0.00111 in coding and in noncoding perigenic DNA, respectively, lower than estimates in the autogamous model species Arabidopsis thaliana. Haplotype analysis of SNP-containing fragments revealed a deficiency of haplotypes vs. the number that would be anticipated at linkage equilibrium. In 49 fragments with three or more SNPs, five haplotypes were present in one fragment while four or less were present in the remaining 48, thereby supporting the suggestion of relatively limited genetic variation in cultivated soybean. Squared allele-frequency correlations (r(2)) among haplotypes at 54 loci with two or more SNPs indicated low genome-wide LD. The low level of LD and the limited haplotype diversity suggested that the genome of any given soybean accession is a mosaic of three or four haplotypes. To facilitate SNP discovery and the development of a transcript map, subsets of four to six diverse genotypes, whose sequence analysis would permit the discovery of at least 75% of all SNPs present in the 25 genotypes as well as 90% of the common (frequency >0.10) SNPs, were identified.
| S-EPMC1462490 | biostudies-other
Project description:BackgroundWe sought to determine whether socio-economic status (SES) is an independent predictor of outcome following total knee (TKR) and hip (THR) replacement in Australians.MethodsIn this prospective cohort study, we included patients undergoing TKR and THR in a public hospital in whom baseline and 12-month follow-up data were available. SES was determined using the Australian Bureau of Statistics 'Index of Relative Advantage and Disadvantage'. Other independent variables included patients' demographics, comorbidities and procedure-related variables. Outcome measures were the International Knee Society Score and Harris Hip Score pain and function subscales, and the Short Form Health Survey (SF-12) physical and mental component scores.ResultsAmong 1,016 patients undergoing TKR and 835 patients undergoing THR, in multiple regression analysis, SES score was not independently associated with pain and functional outcomes. Female sex, older age, being a non-English speaker, higher body mass index and presence of comorbidities were associated with greater post-operative pain and poorer functional outcomes following arthroplasty. Better baseline function, physical and mental health, and lower baseline level of pain were associated with better outcomes at 12 months. In univariate analysis, for TKR, the improvement in SF-12 mental health score post arthroplasty was greater in patients of lower SES (3.8 ± 12.9 versus 1.5 ± 12.2, p=0.008), with a statistically significant inverse association between SES score and post-operative SF-12 mental health score in linear regression analysis (coefficient-0.28, 95% CI: -0.52 to -0.04, p=0.02).ConclusionsWhen adjustments are made for other covariates, SES is not an independent predictor of pain and functional outcome following large joint arthroplasty in Australian patients. However, relative to baseline, patients in lower socioeconomic groups are likely to have greater mental health benefits with TKR than more privileged patients. Large joint arthroplasty should be made accessible to patients of all SES.
| S-EPMC4107720 | biostudies-literature
Project description:A large number of genes associated with various cancer types contain single nucleotide polymorphisms (SNPs). SNPs are located in gene promoters, exons, introns as well as 5'- and 3'- untranslated regions (UTRs) and affect gene expression by different mechanisms. These mechanisms depend on the role of the genetic elements in which the individual SNPs are located. Moreover, alterations in epigenetic regulation due to gene polymorphisms add to the complexity underlying cancer susceptibility related to SNPs. In this systematic review, we discuss the various genetic and epigenetic mechanisms involved in determining cancer susceptibility related to various SNPs located in different genetic elements. We also discuss the diagnostic potential of these SNPs and the focus for future studies.
| S-EPMC5746410 | biostudies-other
Project description:Infants and children with chronic lung disease of prematurity (CLDP) are at increased risk for respiratory morbidities. We sought to determine (1) whether socio-economic status, race/ethnicity, and/or sex are risk factors for respiratory morbidities and (2) whether disparities in care existed for major therapy decisions such as home supplemental oxygen and gastrostomy tubes as well as initial length of stay in the neonatal intensive care unit.Between January 2008 and February 2010 sociodemographic and respiratory morbidity data were collected on premature (<32 weeks gestation) infants and children (<3 years old) with CLDP. Associations between risk factors and respiratory morbidities and treatment parameters were examined using adjusted regression models.Data were collected on 135 subjects (gestational age: 26.2±2.0 weeks). Self-reported non-Whites were more likely to report rescue medication use in the past 7 days [adjusted OR: 2.87 (1.28-6.45), P=0.011] and the use of systemic steroids for respiratory symptoms since the last clinic visit [adjusted OR: 2.12 (1.02-4.43), P=0.045]. Lower median household income was associated with increased activity limitations [adjusted OR: 2.79 (1.16-6.70), P=0.022] and public insurance coverage was associated with a decreased risk for hospitalizations [adjusted OR: 0.36 (0.13-0.98), P=0.045]. Major therapy decisions were not associated with disparities of care.A key finding was that non-Whites were more likely to report rescue medication and systemic steroid use than Whites, but there was no difference in the frequency of respiratory symptoms or preventative inhaled corticosteroid use. Etiologies for these findings remain unclear and require further research.
| S-EPMC3115434 | biostudies-literature
Project description:Pan-genomic open reading frames (ORFs) potentially carry protein-coding gene or coding variant information in a population. In this study, we suggest that pan-genomic ORFs are promising to be utilized in estimation of heritability and genomic prediction. A Saccharomyces cerevisiae dataset with whole-genome SNPs, pan-genomic ORFs, and the copy numbers of those ORFs is used to test the effectiveness of ORF data as a predictor in three prediction models for 35 traits. Our results show that the ORF-based heritability can capture more genetic effects than SNP-based heritability for all traits. Compared to SNP-based genomic prediction (GBLUP), pan-genomic ORF-based genomic prediction (OBLUP) is distinctly more accurate for all traits, and the predictive abilities on average are more than doubled across all traits. For four traits, the copy number of ORF-based prediction(CBLUP) is more accurate than OBLUP. When using different numbers of isolates in training sets in ORF-based prediction, the predictive abilities for all traits increased as more isolates are added in the training sets, suggesting that with very large training sets the prediction accuracy will be in the range of the square root of the heritability. We conclude that pan-genomic ORFs have the potential to be a supplement of single nucleotide polymorphisms in estimation of heritability and genomic prediction.
| S-EPMC7470747 | biostudies-literature
Project description:Several single-nucleotide polymorphisms (SNPs) associated with breast cancer risk have been identified through genome-wide association studies (GWAS). We investigated whether eight risk SNPs identified in GWAS were associated with breast cancer disease-free survival (DFS) and overall survival (OS) rates.A cohort of 739 white women with early-stage breast cancer was genotyped for eight GWAS-identified SNPs (rs2981582, rs1219648 [FGFR2], rs3803662, rs12443621, rs8051542 [TOX3], rs999737 [RAD51L1], rs6504950 [17q23], and rs4973768 [3p24]). Relationships between SNPs and breast cancer outcomes were evaluated using Cox proportional hazard regression models. The cumulative effects of SNPs on breast cancer outcomes were assessed by computing the number of at-risk genotypes.At a median follow-up of 121 months (range: 188-231 months) for survivors, 237 deaths (32%) and 186 breast cancer events (25%) were identified among the 739 patients. After adjusting for age, clinical stage, and treatment, rs12443621 (16q12; p = .03) and rs6504950 (17q23; p = .008) were prognostic for OS but not DFS. A higher risk for death was also found in the multivariable analysis of patients harboring three or four at-risk genotypes of the GWAS SNPs compared to patients carrying two or less at-risk genotypes (hazard ratio: 1.60, 95% confidence interval: 1.23-2.24; p = .0008).The study results suggest that previously identified breast cancer risk susceptibility loci, rs12443621 (16q12) and rs6504950 (17q23), may influence breast cancer prognosis or comorbid conditions associated with overall survival. The precise molecular mechanisms through which these risk SNPs, as well as others that were not included in the analysis, influence clinical outcomes remain to be determined.
| S-EPMC3662839 | biostudies-literature
Project description:PurposeTo explore whether it is possible to predict the number and quality of the embryo using a few particular hTERT SNPs.MethodsWe included 997 Han Chinese women who were genetically unrelated and underwent assisted reproduction using IVF from September 2014 to December 2015. DNA was genotyped by using TaqMan real-time quantitative PCR.ResultsAmong the 997 patients, individuals with the CC genotype of rs2075786 had a significantly lower number of good-quality embryos than those with the TT+TC genotypes. Compared with the CT+CC genotype carriers, patients carrying the TT genotype of rs2853677 had a significantly lower number of oocytes retrieved, mature oocytes and available embryos. Among the 750 patients aged ≤ 35 years, individuals with the AA+AG genotypes of rs2853691 had a significantly higher number of good-quality embryos than those with the GG genotype. The haplotype analysis showed that the TTTG (rs2853672/rs2853669/rs2735940/rs2736108) haplotype was more likely to lead to more than three good-quality embryos in patients aged ≤ 35 years.ConclusionsOur study suggests that the hTERT SNP is associated with IVF outcomes.
| S-EPMC6439048 | biostudies-literature
Project description:We previously showed that prototype macaque-tropic human immunodeficiency virus type 1 (HIV-1) acquired nonsynonymous growth-enhancing mutations within a narrow genomic region during the adaptation process in macaque cells. These adaptive mutations were clustered in the 3' region of the pol gene, encoding a small portion of the C-terminal domain of integrase (IN). Mutations in HIV-1 IN have been reported to have pleiotropic effects on both the early and late phases in viral replication. cis-acting functions in the IN-coding sequence for viral gene expression have also been reported. We here demonstrated that the adaptive mutations promoted viral growth by increasing virion production with no positive effects on the early replication phase. Synonymous codon alterations in one of the adaptive mutations influenced virion production levels, which suggested nucleotide-dependent regulation. Indeed, when the single-nucleotide natural polymorphisms observed in the 3' regions of 196 HIV-1/simian immunodeficiency virus (SIVcpz) pol genes (nucleotides [nt] 4895 to 4929 for HIV-1 NL4-3) were introduced into macaque- and human-tropic HIV-1 clones, more than half exhibited altered replication potentials. Moreover, single-nucleotide mutations caused parallel increases or decreases in the expression levels of viral late proteins and viral replication potentials. We also showed that the overall expression profiles of viral mRNAs were markedly changed by single-nucleotide mutations. These results demonstrate that the 3' region of the HIV-1 pol gene (nt 4895 to 4929) can alter viral replication potential by modulating the expression pattern of viral mRNAs in a nucleotide-dependent manner.Viruses have the plasticity to adapt themselves under various constraints. HIV-1 can mutate and evolve in growth-restrictive cells by acquiring adaptive changes in its genome. We have previously identified some growth-enhancing mutations in a narrow region of the IN-coding sequence, in which a number of cis-acting elements are located. We now focus on the virological significance of this pol gene region and the mechanistic basis underlying its effects on viral replication. We have found several naturally occurring synonymous mutations within this region that alter viral replication potentials. The effects caused by these natural single-nucleotide polymorphisms are linked to the definite expression patterns of viral mRNAs. We show here that the nucleotide sequence of the pol gene (nucleotides 4895 to 4929 for HIV-1 NL4-3) plays an important role in HIV-1 replication by modulating viral gene expression.
| S-EPMC3993728 | biostudies-literature