scholarly journals Population-based analysis of ocularChlamydia trachomatisin trachoma-endemic West African communities identifies genomic markers of disease severity

2017 ◽  
Author(s):  
AR Last ◽  
H Pickering ◽  
Ch Roberts ◽  
F Coll ◽  
J Phelan ◽  
...  
Keyword(s):  
Disease Severity ◽  
Disease Transmission ◽  
Population Based ◽  
Genomic Diversity ◽  
Ocular Tissue ◽  
Nucleotide Polymorphisms ◽  
Functional Protein ◽  
Transmitted Infection ◽  
Genomic Markers ◽  
Treatment Naïve

ABSTRACTChlamydia trachomatis(Ct) is the most common infectious cause of blindness and bacterial sexually transmitted infection worldwide. UsingCtwhole genome sequences obtained directly from conjunctival swabs, we studiedCtgenomic diversity and associations betweenCtgenetic polymorphisms with ocular localization and disease severity in a treatment-naïve trachoma-endemic population in Guinea Bissau, West Africa. All sequences fall within the T2 ocular clade phylogenetically. This is consistent with the presence of the characteristic deletion intrpAresulting in a truncated non-functional protein and the ocular tyrosine repeat regions present intarPassociated with ocular tissue localization. We have identified twenty-oneCtnon-synonymous single nucleotide polymorphisms (SNPs) associated with ocular localization, including SNPs withinpmpD(OR=4.07,p*=0.001) andtarP(OR=0.34,p*=0.009). Eight SNPs associated with disease severity were found inyjfH (rlmB)(OR=0.13,p*=0.037),CTA0273(OR=0.12,p*=0.027),trmD(OR=0.12,p*=0.032),CTA0744(OR=0.12,p*=0.041),glgA(OR=0.10,p*=0.026),alaS(OR=0.10,p*=0.032),pmpE(OR=0.08,p*=0.001) and the intergenic regionCTA0744-CTA0745(OR=0.13,p*=0.043). This study demonstrates the extent of genomic diversity within a naturally circulating population of ocularCt, and the first to describe novel genomic associations with disease severity. These findings direct investigation of host-pathogen interactions that may be important in ocularCtpathogenesis and disease transmission.

scholarly journals A microRNA panel compared to environmental and polygenic scores for colorectal cancer risk prediction

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Janhavi R. Raut ◽  
Ben Schöttker ◽  
Bernd Holleczek ◽  
Feng Guo ◽  
Megha Bhardwaj ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Prediction ◽  
Risk Score ◽  
Characteristic Curve ◽  
Predictive Ability ◽  
Population Based ◽  
Polygenic Risk Score ◽  
Nucleotide Polymorphisms ◽  
Polygenic Scores

AbstractCirculating microRNAs (miRNAs) could improve colorectal cancer (CRC) risk prediction. Here, we derive a blood-based miRNA panel and evaluate its ability to predict CRC occurrence in a population-based cohort of adults aged 50–75 years. Forty-one miRNAs are preselected from independent studies and measured by quantitative-real-time-polymerase-chain-reaction in serum collected at baseline of 198 participants who develop CRC during 14 years of follow-up and 178 randomly selected controls. A 7-miRNA score is derived by logistic regression. Its predictive ability, quantified by the optimism-corrected area-under-the-receiver-operating-characteristic-curve (AUC) using .632+ bootstrap is 0.794. Predictive ability is compared to that of an environmental risk score (ERS) based on known risk factors and a polygenic risk score (PRS) based on 140 previously identified single-nucleotide-polymorphisms. In participants with all scores available, optimism-corrected-AUC is 0.802 for the 7-miRNA score, while AUC (95% CI) is 0.557 (0.498–0.616) for the ERS and 0.622 (0.564–0.681) for the PRS.

scholarly journals Independent and combined associations between fast-food outlet exposure and genetic risk for obesity: a population-based, cross-sectional study in the UK

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Thomas Burgoine ◽  
Pablo Monsivais ◽  
Stephen J. Sharp ◽  
Nita G. Forouhi ◽  
Nicholas J. Wareham
Keyword(s):  
Genetic Risk ◽  
Fast Food ◽  
Genetic Risk Score ◽  
Population Based ◽  
Overweight And Obesity ◽  
Nucleotide Polymorphisms ◽  
Food Outlet ◽  
Cross Sectional ◽  
Fast Food Outlet ◽  
Common Genetic Variants

Abstract Background Characteristics of the built environment, such as neighbourhood fast-food outlet exposure, are increasingly recognised as risk factors for unhealthy diet and obesity. Obesity also has a genetic component, with common genetic variants explaining a substantial proportion of population-level obesity susceptibility. However, it is not known whether and to what extent associations between fast-food outlet exposure and body weight are modified by genetic predisposition to obesity. Methods We used data from the Fenland Study, a population-based sample of 12,435 UK adults (mean age 48.6 years). We derived a genetic risk score associated with BMI (BMI-GRS) from 96 BMI-associated single nucleotide polymorphisms. Neighbourhood fast-food exposure was defined as quartiles of counts of outlets around the home address. We used multivariable regression models to estimate the associations of each exposure, independently and in combination, with measured BMI, overweight and obesity, and investigated interactions. Results We found independent associations between BMI-GRS and risk of overweight (RR = 1.34, 95% CI 1.23–1.47) and obesity (RR = 1.73, 95% CI 1.55–1.93), and between fast-food outlet exposure and risk of obesity (highest vs lowest quartile RR = 1.58, 95% CI 1.21–2.05). There was no evidence of an interaction of fast-food outlet exposure and genetic risk on BMI (P = 0.09), risk of overweight (P = 0.51), or risk of obesity (P = 0.27). The combination of higher BMI-GRS and highest fast-food outlet exposure was associated with 2.70 (95% CI 1.99–3.66) times greater risk of obesity. Conclusions Our study demonstrated independent associations of both genetic obesity risk and neighbourhood fast-food outlet exposure with adiposity. These important drivers of the obesity epidemic have to date been studied in isolation. Neighbourhood fast-food outlet exposure remains a potential target of policy intervention to prevent obesity and promote the public’s health.

ΔF508 Genotype Does Not Predict Disease Severity in an Ethnically Diverse Cystic Fibrosis Population

PEDIATRICS ◽  
1994 ◽  
Vol 93 (1) ◽  
pp. 114-118
Author(s):  
Lucille A. Lester ◽  
Jerome Kraut ◽  
John Lloyd-Still ◽  
Theodore Karrison ◽  
Carol Mott ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Disease Severity ◽  
Ethnically Diverse ◽  
Clinical Parameter ◽  
Population Based ◽  
Age At Diagnosis ◽  
Chest Roentgenogram ◽  
Sweat Chloride ◽  
Cystic Fibrosis Population ◽  
Cftr Mutations

Objective. As part of a study to determine population-based frequencies of CFTR mutations in an ethnically diverse, midwestern cystic fibrosis (CF) population, clinical histories were studied in 119 CF patients. Methodology. We sought to examine the association between genotype as characterized by the ΔF508 and 11 other commonly occurring mutations and clinical parameters including age at diagnosis, clinical presentation, sweat chloride level, chest roentgenogram score, clinical scores, pulmonary function test results, percent weight for height, and presence of associated CF complications. Results. Age at diagnosis of CF was significantly associated with homozygosity for ΔF508 (mean age at diagnosis ± SE: 1.7 ± 0.3 years for ΔF508/ΔF508 vs 3.9 ± 0.9 years for ΔF508/other and other/other; P = .03). No other age-adjusted clinical parameter was significantly associated with ΔF508 or any other genotype. Conclusion. These data suggest that in this sample of CF patients, ΔF508 genotype is not predictive of disease severity. The lack of association between disease severity and genotype in this ethnically diverse sample may reflect the presence of more severe undetected mutations in our sample, or the effects of modifying genes at other, non-CF loci.

scholarly journals Genetic Association and Gene-gene interaction ofHAS2,HABP1andHYAL3Implicate Hyaluronan Metabolic Genes in Glaucomatous Neurodegeneration

2012 ◽  
Vol 33 (3) ◽  
pp. 145-154 ◽  
Author(s):  
Kaustuv Basu ◽  
Abhijit Sen ◽  
Kunal Ray ◽  
Ilora Ghosh ◽  
Kasturi Datta ◽  
...  
Keyword(s):  
Open Angle Glaucoma ◽  
Gene Interaction ◽  
Negative Control ◽  
Ocular Tissue ◽  
Allelic Association ◽  
Nucleotide Polymorphisms ◽  
Aqueous Humor Outflow ◽  
High Tension ◽  
Potential Association ◽  
Genotypic Association

Hyaluronan (HA) plays a significant role in maintaining aqueous humor outflow in trabecular meshwork, the primary ocular tissue involved in glaucoma. We examined potential association of the single nucleotide polymorphisms (SNPs) of the HA synthesizing gene – hyaluronan synthase 2 (HAS2), hyaluronan binding protein 1 (HABP1) and HA catabolic gene hyaluronidase 3 (HYAL3) in the primary open angle glaucoma (POAG) patients in the Indian population. Thirteen tagged SNPs (6 forHAS2, 3 forHABP1and 4 forHYAL3) were genotyped in 116 high tension (HTG), 321 non-high tension glaucoma (NHTG) samples and 96 unrelated, age-matched, glaucoma-negative, control samples. Allelic and genotypic association were analyzed by PLINK v1.04; haplotypes were identified using PHASE v2.1 and gene-gene interaction was analyzed using multifactor dimensionality reduction (MDR) v2.0. An allelic association (rs6651224;p= 0.03; OR: 0.49; 95% CI: 0.25–0.94) was observed at the second intron (C>G) ofHAS2both for NHTG and HTG. rs1057308 revealed a genotypic association (p= 0.03) at the 5’ UTR ofHAS2with only HTG. TCT haplotype (rs1805429 – rs2472614 – rs8072363) inHABP1and TTAG and TTGA (rs2285044 – rs3774753 – rs1310073 – rs1076872) inHYAL3were found to be significantly high (p< 0.05) both for HTG and NHTG compared to controls. Gene-gene interaction revealedHABP1predominantly interacts withHAS2in HTG while it associates with bothHYAL3andHAS2in NHTG. This is the first genetic evidence, albeit from a smaller study, that the natural polymorphisms in the genes involved in hyaluronan metabolism are potentially involved in glaucomatous neurodegeneration.

scholarly journals INFLUENCE ON HOMEOSTASIS AS THE CRITERION FOR SELECTING SINGLE NUCLEOTIDE POLYMORPHISMS FOR THE STUDY OF METABOLIC SYNDROM IN THE KAZAKH POPULATION

REPORTS ◽  
2020 ◽  
Vol 5 (333) ◽  
pp. 86-93
Author(s):  
V.V. Benberin ◽  
◽  
T.A. Voshchenkova ◽  
A.A. Nagymtayeva ◽  
A.S. Sibagatova ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Traditional Approach ◽  
Population Based ◽  
Malignant Neoplasms ◽  
Nucleotide Polymorphisms ◽  
Genetic Determinants ◽  
Single Nucleotide ◽  
Sequence Of Events ◽  
Kazakh Population ◽  
Symptom Complex

Metabolic syndrome (MS) is increasingly cited as the world's leading health risk. The sequence of events toward multimorbidity in most cases passes through MS. According to the research, MS heritability ranges from 23 to 27% in Europeans, and 51 to 60% in Asians. The purpose of the review: to form a strategy for the selection of single nucleotide polymorphisms (SNPs) for the study of MS in the Kazakh population based on the effect of SNPs on homeostasis indicators The stable symptom complex of MS is a complicated dynamic system of successive accumulations of dysmetabolic disorders of homeostasis. This system starts the development of subsequent age-associated diseases), such as cardiometabolic, neurodegenerative, and malignant neoplasms. The system for selecting SNPs for the MS study, proposed on the basis of the concept of homeostasis dysfunction, assumes, in conditions of limited resources, to see the greatest level of their influence within the conditional framework of three genetic models of homeostasis dysregulation: insulin resistance , oxidative stress, and chronic inflammation. This approach is fundamentally different from the traditional approach involving candidate genes. It is expected that scientific research in this direction will contribute not only to the understanding of general biological processes, but also to the targeted search for genetic determinants and for new opportunities for personalized interventions.

scholarly journals Single Nucleotide Polymorphisms in HOTAIR Are Related to Breast Cancer Risk and Prognosis in the Northeastern Chinese Population

2021 ◽  
Vol 11 ◽  
Author(s):  
Zheng Lv ◽  
Changgui Kou ◽  
Naifei Chen ◽  
Lin Jia ◽  
Xu Sun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Single Nucleotide Polymorphisms ◽  
Chinese Population ◽  
Noncoding Rna ◽  
Disease Free Survival ◽  
Population Based ◽  
Clinicopathological Characteristics ◽  
Nucleotide Polymorphisms ◽  
Binary Logistic Regression Model ◽  
Single Nucleotide

BackgroundThe long noncoding RNA HOX transcript antisense RNA (HOTAIR) is highly expressed in breast cancer (BC) tissues and is associated with the recurrence and metastasis of BC. Until now, the results of studies on associations between several functional single nucleotide polymorphisms(SNPs) (rs920778, rs1899663, and rs4759314) in HOTAIR with BC susceptibility carried out in different regions of China are still inconsistent. There is no study on correlation between HOTAIR SNPs and prognosis of Chinese population. Therefore, we investigated the relationship between HOTAIR SNPs and susceptibility to and prognosis of BC.MethodWe conducted a population-based case-control study involving 828 BC cases and 905 healthy controls. Peripheral blood DNA was used for genotyping. The association between HOTAIR genotypes and BC risk were estimated by odds ratios (ORs) computed using the binary logistic regression model. The relationships between HOTAIR SNPs and clinicopathological features were tested by Pearson’s chi-square test or Fisher’s exact test. Survival was analyzed using the Kaplan-Meier method.ResultsThe functional rs920778 genetic variant increased BC risk in the codominant model. Individuals with the rs920778 GG genotype had an OR of 2.426 (95% confidence interval [CI] = 1.491–3.947, P &lt; 0.001) for developing BC compared to individuals with the AA genotype. Individuals with the AG genotype had an OR of 1.296 (95% CI = 1.040–1.614, P = 0.021) for developing BC compared to individuals with the AA genotype. Individuals with the rs4759314 GA genotype had a lower BC risk than individuals with the rs4759314 AA/GG genotype (OR = 0.566, 95% CI = 0.398–0.803, P = 0.001). The rs1899663 genotype had no correlation with BC susceptibility. Haplotypes composed of rs920778–rs1899663 and rs920778–rs1899663–rs4759314 could increase BC risk (all P &lt; 0.001). There were no statistically significant associations between HOTAIR SNPs and clinicopathological characteristics. The rs920778 GG/AG genotypes were associated with worse disease-free survival (DFS) (p = 0.012), and the rs4759314 GA genotype was associated with worse DFS and overall survival (OS) (p = 0.011).ConclusionHOTAIR SNPs(rs920778 and rs4759314) are significantly related to BC susceptibility and prognosis in the northeastern Chinese population, indicating the significance in the occurrence and development of BC.

scholarly journals Investigating the effects of accelerated partner therapy (APT) on chlamydia transmission in Britain: a mathematical modelling study

2020 ◽  
Author(s):  
Christian L Althaus ◽  
Catherine H Mercer ◽  
Jackie A Cassell ◽  
Claudia S Estcourt ◽  
Nicola Low
Keyword(s):  
Sexual Activity ◽  
Control Strategies ◽  
Controlled Trial ◽  
Partner Notification ◽  
Cluster Randomised Controlled Trial ◽  
Credible Interval ◽  
Population Based ◽  
Transmission Model ◽  
Transmitted Infection ◽  
Potential Increase

Understanding the effects of partner notification (PN) on the transmission of chlamydia, the most prevalent bacterial sexual transmitted infection worldwide, is critical for implementing optimal control strategies. Accelerated partner therapy (APT) aims to increase the numbers of partners treated and reduce the time to partner treatment. Our objective was to study the effects of APT interventions on partner treatment and chlamydia transmission in order to better understand the results of LUSTRUM, an APT cross-over cluster randomised controlled trial in the UK. We developed a novel deterministic, population-based chlamydia transmission model including the process of PN. We considered a population aged 16-34 years and calibrated the model to sexual behaviour data between people of the opposite-sex and chlamydia prevalence data reported by 3,671 participants in Britain's third National Survey of Sexual Attitudes and Lifestyles (Natsal-3, 2010-2012) using Approximate Bayesian Computation (ABC). We investigated the potential effects of APT on chlamydia transmission by increasing the number of treated partners and reducing the time to partner treatment compared to standard PN. The median prevalence of chlamydia in the model was 1.84% (95% credible interval, CrI: 1.60%-2.62%) in women and 1.78% (95% CrI: 1.13%-2.14%) in men. Chlamydia positivity was highest in partners of symptomatic index cases with low sexual activity. Infected partners were typically asymptomatic and belonged to the high sexual activity group, i.e., are naturally those infected individuals that will contribute most to onward transmission. Reducing the time to partner treatment without achieving higher numbers of partners treated had only minor effects on reducing chlamydia prevalence. In contrast, the model predicts that a potential increase in the number of partners treated from current levels in Britain (0.51, 95% CrI: 0.21-0.80) by 25% would reduce chlamydia prevalence by 18% (95% CrI: 5%-44%) in both women in men within 5 years. These results suggest that APT, through a potential increase in the proportion of partners treated, would be an effective method to reduce ongoing chlamydia transmission in Britain.

scholarly journals Characterization of Mycobacterium tuberculosis Isolates from Patients in Houston, Texas, by Spoligotyping

2000 ◽  
Vol 38 (2) ◽  
pp. 669-676 ◽  
Author(s):  
Hanna Soini ◽  
Xi Pan ◽  
Amol Amin ◽  
Edward A. Graviss ◽  
Anees Siddiqui ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Population Based ◽  
Nucleotide Polymorphisms ◽  
Genetic Groups ◽  
Tuberculosis Epidemiology ◽  
New Information ◽  
Catalase Peroxidase ◽  
A Subunit ◽  
Group 2 ◽  
Group 1

Mycobacterium tuberculosis isolates (n= 1,429) from 1,283 patients collected as part of an ongoing population-based tuberculosis epidemiology study in Houston, Texas, were analyzed by spoligotyping and IS6110 profiling. The isolates were also assigned to one of three major genetic groups on the basis of nucleotide polymorphisms located at codons 463 and 95 in the genes (katG and gyrA) encoding catalase-peroxidase and the A subunit of DNA gyrase, respectively. A total of 225 spoligotypes were identified in the 1,429 isolates. There were 54 spoligotypes identified among 713 isolates (n= 623 patients) assigned to 73 IS6110 clusters. In addition, among 716 isolates (n = 660 patients) with unique IS6110 profiles, 200 spoligotypes were identified. No changes were observed either in the IS6110 profile or in the spoligotype for the 281 isolates collected sequentially from 133 patients. Five instances in which isolates with slightly different spoligotypes had the same IS6110 profile were identified, suggesting that in rare cases isolates with different spoligotypes can be clonally related. Spoligotypes correlated extremely well with major genetic group designations. Only three very similar spoligotypes were shared by isolates from genetic groups 2 and 3, and none was shared by group 1 and group 2 organisms or by group 1 and group 3 organisms. All organisms belonging to genetic groups 2 and 3 failed to hybridize with spacer probes 33 to 36. Taken together, the results support the existence of three distinct genetic groups of M. tuberculosis organisms and provide new information about the relationship between IS6110 profiles, spoligotypes, and major genetic groups of M. tuberculosis.

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