scholarly journals MP82-14 SINGLE NUCLEOTIDE POLYMORPHISMS AND RISK OF PROSTATE CANCER: DEVELOPMENT AND VALIDATION OF A NOVEL GENETIC RISK SCORE FOR INDIVIDUALIZED SCREENING AND DIAGNOSTIC PROGRAMMES

2018 ◽  
Vol 199 (4S) ◽  
Author(s):  
Vito Cucchiara ◽  
Vincenzo Mirone ◽  
Dejan Lazarevic ◽  
Davide Cittaro ◽  
Giovanni Tonon ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Single Nucleotide Polymorphisms ◽  
Risk Score ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Cancer Development ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Prostate Cancer Development ◽  
Development And Validation

Will patient’s genetic profile help to choose treatment method of atrial fibrillation?

2019 ◽  
Vol 3 (52) ◽  
pp. 29-30
Author(s):  
Artur Fuglewicz
Keyword(s):  
Atrial Fibrillation ◽  
Single Nucleotide Polymorphisms ◽  
Risk Score ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Treatment Method ◽  
Genetic Profile ◽  
Nucleotide Polymorphisms ◽  
Genetic Score ◽  
Single Nucleotide

The paper comments an attempt of genetic score creation of potential atrial fibrillation ablation failure or recurrence AF. This genetic risk score is based on single nucleotide polymorphisms (SNPs) analysis.

Causal associations of obesity with chronic kidney disease and arterial stiffness: a Mendelian randomization study

2021 ◽  
Author(s):  
Chaojie Ye ◽  
Lijie Kong ◽  
Zhiyun Zhao ◽  
Mian Li ◽  
Shuangyuan Wang ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Standard Deviation ◽  
Kidney Disease ◽  
Single Nucleotide Polymorphisms ◽  
Arterial Stiffness ◽  
Genetic Risk ◽  
Mendelian Randomization ◽  
Genetic Risk Score ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

Abstract Purpose Observational studies have associated obesity with chronic kidney disease (CKD) and arterial stiffness, but the causality remains unclear. We aimed to investigate the causality of obesity with CKD and arterial stiffness using Mendelian randomization (MR) analysis. Methods We genotyped 14 body mass index (BMI)-associated variants validated in East Asians in 11384 Chinese adults. A genetic risk score based on the 14 variants and the 14 individual single nucleotide polymorphisms were respectively used as instrumental variables (IVs). CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m 2. Arterial stiffness was defined as brachial-ankle pulse wave velocity >1550 cm/s. Results Using the genetic risk score as the IV, we demonstrated causal relations of each 1-standard deviation increment in BMI with CKD (odds ratio [OR]: 2.36; 95% confidence interval [CI]: 1.11-5.00) and arterial stiffness (OR: 1.71; 95% CI: 1.22-2.39). Using the 14 single nucleotide polymorphisms individually as IVs, each 1-standard deviation increment in BMI casually associated with CKD (OR: 2.58; 95% CI: 1.39-4.79) and arterial stiffness (OR: 1.87; 95% CI: 1.24-2.81) in the inverse-variance weighted analysis, and MR-Egger regression revealed no evidence of horizontal pleiotropy (Both P for intercept≥0.34). The causality between obesity and CKD was validated in two-sample MR analysis among Europeans (681275 of Genetic Investigation of ANthropometric Traits and 133413 of CKD Genetics). Conclusions This study provided novel insights into causality of obesity with CKD and arterial stiffness, highlighting the importance of weight management for primary prevention and control of subclinical vascular diseases.

scholarly journals Single Nucleotide Polymorphisms and Thromboembolism in Acute Lymphoblastic Leukemia — a NOPHO ALL2008 Study

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 143-143 ◽  
Author(s):  
Kirsten Brunsvig Jarvis ◽  
Marissa Le Blanc ◽  
Morten Tulstrup ◽  
Ellen Ruud ◽  
Ruta Tuckuviene ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Single Nucleotide Polymorphisms ◽  
Risk Score ◽  
Genetic Risk ◽  
Lymphoblastic Leukemia ◽  
European Ancestry ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Risk Alleles ◽  
All Treatment

Abstract Introduction: Thromboembolism (TE) is a major toxicity of acute lymphoblastic leukemia (ALL) treatment and contributes to substantial morbidity and mortality. Several germline DNA variants have been associated with TE in adults without cancer. A meta-analysis of genome-wide association studies on TE by Germain et al. (Am J Hum Genet 2015) identified single nucleotide polymorphisms (SNPs) in 8 genes that contribute to increased risk of TE in adults (ABO,F2, F5,F11, FGG,PROCR,TSPAN15, and SLC44A2). De Haan et al. (Blood 2012) found that SNPs in 5 of these (F5, F2, F11, FGG, and ABO) predicted TE almost as well as a 31 SNP-based risk score. However, the impact of these SNPs in patients with cancer, particularly in children, remains uncertain. Materials and methods: The Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol for children and adults (1-45 years) included a 3-drug induction (vincristine, doxorubicin, glucocorticosteroid) followed by exposure to asparaginase (1,000 IU/m.sq. i.m.) from week 5 until week 33 (details of therapy in Toft, Leukemia 2018). We collected germline DNA and prospectively registered TE events on 1482 children and adults diagnosed with ALL and treated according to the ALL2008 protocol in seven Nordic and Baltic countries (7/2008-7/2016) (Rank, Blood 2018). Inclusion criteria for TE were i) symptomatic venous or arterial TE confirmed by imaging or by autopsy for TE diagnosed post mortem or ii) asymptomatic TE confirmed by imaging due to other non-TE symptoms and treated with systemic anticoagulation. Based on previously published data and a priori power calculations, we selected and genotyped 5 SNPs: F5 rs6025 (risk allele frequency (RAF) 0.05), F11 rs2036914 (RAF 0.52), FGG rs2066865 (RAF 0.22), and ABO SNPs rs8176719 (RAF 0.39) and rs2519093 (RAF 0.24). Three SNPs (F5 and the two ABO SNPs) were found by imputation, which was done on a subset of patients with European ancestry and included in the NOPHO ALL2008 protocol (N = 1229). We constructed genetic risk scores using a combination of the SNPs. Results: During the ALL treatment period 107 of 1482 patients developed TE (2.5-year cumulative incidence 7.3%, 95% confidence interval (CI) 5.9-8.5). In multivariate Cox regression analysis controlling for age, gender, presence of mediastinal mass and enlarged lymph nodes (N = 1192, whereof TE events 84), we found statistically significant associations with TE development for SNPs F5 rs6025 (hazard ratio (HR) 2.96, 95% CI 1.59-5.48), F11 rs2036914 (HR 1.62, 95% CI 1.18-2.24), and FGG rs2066865 (HR 1.40 95% CI 1.01-1.95), whereas there were no significant associations with ABO SNPs rs8176719 (HR 0.98, 95% CI 0.64-1.51) or rs2519093 (HR 1.06, 95% CI 0.65-1.73). An unweighted 3 SNP risk score based on SNPs F5, F11, and FGG was associated with TE development (HR 1.59, 95% CI 1.27-1.98) (Figure 1). Twenty-six of 217 patients with ≥3 risk alleles developed TE (12.0%, 95% CI 8.1-17.2), compared to 62 of 1007 patients with <3 risk alleles (6.2%, 95% CI 4.8-7.9). The association was strongest in the adolescent age group (10-18 years; HR 1.88, 95% CI 1.35-2.63). Thirteen of 43 adolescents with ≥3 risk alleles developed TE (30.2%, 95% CI 17.8-46.3), compared to 20 of 182 adolescents with <3 risk alleles (11.0%, 95% CI 7.0-16.7) (Figure 2). In adults (>18 years) the proportion who developed TE was quite high in both the group with ≥3 risk alleles (23.5%, 95% CI 7.8-50.2) and with <3 risk alleles (17.6% 95%CI 11.1-26.3). In children (1-10 years) the proportion who developed TE was low in both the group with ≥3 risk alleles (5.7%, 95% CI 2.8-10.9) and with <3 risk alleles (3.2%, 95% CI 2.1-4.8). A weighted 3 SNP genetic risk score based on estimated odds ratios from literature for SNPs F5, F11 and FGG was also associated with TE development (HR 2.84, 95% CI 1.85-4.36). Again, the association was strongest in adolescents (HR 4.20, 95% CI 2.22-7.94). Conclusion: Based on the strong association between F5 rs6025, F11 rs2036914, and FGG rs2066865 and TE development, not least for adolescents, future preventive measures for TE should target adolescents with ≥3 risk alleles as well as any adults ≥18 years. Disclosures No relevant conflicts of interest to declare.

scholarly journals Association between Cognitive Function and Large Optic Nerve Cupping, Accounting for Cup-Disc-Ratio Genetic Risk Score

2021 ◽  
Author(s):  
Sasha Kravets ◽  
Rawan Allozi Rupnow ◽  
Abhishek Sethi ◽  
Mark A. Espeland ◽  
Louis R. Pasquale ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Risk Score ◽  
Genetic Risk ◽  
White Women ◽  
Genetic Risk Score ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Unit Increase ◽  
Using Data ◽  
State Examination

AbstractPurposeTo investigate if accounting for a cup-to-disc ratio (CDR) genetic risk score (GRS) modified the association between large CDR and cognitive function among women.DesignThis was a retrospective study using data from the Women’s Health Initiative.MethodsPatients with glaucoma or ocular hypertension were excluded. Large CDR was defined as ≥ 0.6 in either eye. Cognitive function was measured by the Modified Mini-Mental State Examination (3MSE). We used the combined effects from 13 single nucleotide polymorphisms (SNPs) to formulate the GRS for CDR. We used logistic regression to investigate associations between weighted GRS and large CDR, then a linear regression to assess the association between weighted GRS and 3MSE scores, and between weighted GRS, CDR, and 3MSE scores, adjusted for demographic and clinical characteristics.ResultsFinal analyses included 1,196 White women with mean age of 69.60 ± 3.62 years and 7.27% with large CDR. Mean GRS in women with and without large CDR was 1.51 ± 0.31 vs. 1.41 ± 0.36, respectively (p = 0.004). The odds of large CDR for a one unit increase in GRS was 2.30 (95% CI: (1.22, 4.36), p = 0.011). Adding the CDR GRS in the model with CDR and 3MSE, women with large CDR still had statistically significantly lower 3MSE scores than those without large CDR, yielding a predicted mean difference in 3MSE scores of 0.84 (p = 0.007).ConclusionsIndependent of the CDR GRS, women with large CDR had a lower cognitive function.

scholarly journals Single-Nucleotide Polymorphisms Sequencing Identifies Candidate Functional Variants at Prostate Cancer Risk Loci

Genes ◽  
2019 ◽  
Vol 10 (7) ◽  
pp. 547 ◽  
Author(s):  
Peng Zhang ◽  
Lori S. Tillmans ◽  
Stephen N. Thibodeau ◽  
Liang Wang
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Single Nucleotide Polymorphisms ◽  
Protein Binding ◽  
Prostate Cancer Risk ◽  
Sequencing Analysis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Functional Variants ◽  
Dependent Protein

Genome-wide association studies have identified over 150 risk loci that increase prostate cancer risk. However, few causal variants and their regulatory mechanisms have been characterized. In this study, we utilized our previously developed single-nucleotide polymorphisms sequencing (SNPs-seq) technology to test allele-dependent protein binding at 903 SNP sites covering 28 genomic regions. All selected SNPs have shown significant cis-association with at least one nearby gene. After preparing nuclear extract using LNCaP cell line, we first mixed the extract with dsDNA oligo pool for protein–DNA binding incubation. We then performed sequencing analysis on protein-bound oligos. SNPs-seq analysis showed protein-binding differences (>1.5-fold) between reference and variant alleles in 380 (42%) of 903 SNPs with androgen treatment and 403 (45%) of 903 SNPs without treatment. From these significant SNPs, we performed a database search and further narrowed down to 74 promising SNPs. To validate this initial finding, we performed electrophoretic mobility shift assay in two SNPs (rs12246440 and rs7077275) at CTBP2 locus and one SNP (rs113082846) at NCOA4 locus. This analysis showed that all three SNPs demonstrated allele-dependent protein-binding differences that were consistent with the SNPs-seq. Finally, clinical association analysis of the two candidate genes showed that CTBP2 was upregulated, while NCOA4 was downregulated in prostate cancer (p < 0.02). Lower expression of CTBP2 was associated with poor recurrence-free survival in prostate cancer. Utilizing our experimental data along with bioinformatic tools provides a strategy for identifying candidate functional elements at prostate cancer susceptibility loci to help guide subsequent laboratory studies.

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