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Regular, long-term aspirin use may act synergistically with genetic variants, particularly those in mechanistically relevant pathways, to confer a protective effect on colorectal cancer (CRC) risk. We leveraged pooled data from 52 clinical trial, cohort, and case-control studies that included 30,806 CRC cases and 41,861 controls of European ancestry to conduct a genome-wide interaction scan between regular aspirin/nonsteroidal anti-inflammatory drug (NSAID) use and imputed genetic variants. After adjusting for multiple comparisons, we identified statistically significant interactions between regular aspirin/NSAID use and variants in 6q24.1 (top hit rs72833769), which has evidence of influencing expression of TBC1D7 (a subunit of the TSC1-TSC2 complex, a key regulator of MTOR activity), and variants in 5p13.1 (top hit rs350047), which is associated with expression of PTGER4 (codes a cell surface receptor directly involved in the mode of action of aspirin). Genetic variants with functional impact may modulate the chemopreventive effect of regular aspirin use, and our study identifies putative previously unidentified targets for additional mechanistic interrogation.
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Antiinflamatorios no Esteroideos , Neoplasias Colorrectales , Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido Simple , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/tratamiento farmacológico , Antiinflamatorios no Esteroideos/farmacología , Aspirina/farmacología , Subtipo EP4 de Receptores de Prostaglandina E/genética , Subtipo EP4 de Receptores de Prostaglandina E/metabolismo , Masculino , Predisposición Genética a la Enfermedad , Femenino , Estudios de Casos y Controles , Persona de Mediana Edad , Sitios Genéticos , AncianoRESUMEN
BACKGROUND: Menopausal hormone therapy (MHT), a common treatment to relieve symptoms of menopause, is associated with a lower risk of colorectal cancer (CRC). To inform CRC risk prediction and MHT risk-benefit assessment, we aimed to evaluate the joint association of a polygenic risk score (PRS) for CRC and MHT on CRC risk. METHODS: We used data from 28,486 postmenopausal women (11,519 cases and 16,967 controls) of European descent. A PRS based on 141 CRC-associated genetic variants was modeled as a categorical variable in quartiles. Multiplicative interaction between PRS and MHT use was evaluated using logistic regression. Additive interaction was measured using the relative excess risk due to interaction (RERI). 30-year cumulative risks of CRC for 50-year-old women according to MHT use and PRS were calculated. RESULTS: The reduction in odds ratios by MHT use was larger in women within the highest quartile of PRS compared to that in women within the lowest quartile of PRS (p-value = 2.7 × 10-8). At the highest quartile of PRS, the 30-year CRC risk was statistically significantly lower for women taking any MHT than for women not taking any MHT, 3.7% (3.3%-4.0%) vs 6.1% (5.7%-6.5%) (difference 2.4%, P-value = 1.83 × 10-14); these differences were also statistically significant but smaller in magnitude in the lowest PRS quartile, 1.6% (1.4%-1.8%) vs 2.2% (1.9%-2.4%) (difference 0.6%, P-value = 1.01 × 10-3), indicating 4 times greater reduction in absolute risk associated with any MHT use in the highest compared to the lowest quartile of genetic CRC risk. CONCLUSIONS: MHT use has a greater impact on the reduction of CRC risk for women at higher genetic risk. These findings have implications for the development of risk prediction models for CRC and potentially for the consideration of genetic information in the risk-benefit assessment of MHT use.
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Neoplasias Colorrectales , Predisposición Genética a la Enfermedad , Humanos , Femenino , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/epidemiología , Persona de Mediana Edad , Estudios de Casos y Controles , Factores de Riesgo , Anciano , Terapia de Reemplazo de Hormonas/efectos adversos , Medición de Riesgo , Menopausia , Posmenopausia , Terapia de Reemplazo de Estrógeno/efectos adversosRESUMEN
A data-driven prediction tool has the potential to provide early warning of an asthma attack and improve asthma management and outcomes. Most previous machine learning (ML)-based studies for asthma attack prediction have reported a severe class imbalance, with major implications for model performance. We aimed to undertake a systematic comparison of several class imbalance handling techniques in the context of risk prediction models for asthma prognosis. We used data from 9,835 asthma patients extracted from the Medical Information Mart for Intensive Care (MIMIC) IV database and deployed five class imbalance handling methods based on synthetic minority oversampling technique (SMOTE) and cost function customisation. We then compared their performances in improving two-class classifier models developed using logistic regression (LR) and extreme gradient boosting (XGBoost) for three different prediction tasks with varying severity of class imbalance (proportion of majority class ranging from 90.86% to 98.98%). The cost function customisation technique substantially outperformed the SMOTE-based methods in all tasks. XGBoost combined with cost function customisation achieved the highest prediction performance for the outcome with the most extreme class imbalance ratio (AUC = 0.72). Our findings suggest that the cost function customisation-based approach to tackle class imbalance provides substantially better performance compared to oversampling in the context of asthma management.Clinical Relevance- This study underscores the challenge of class imbalance in the context of prediction tools to improve asthma management and outcomes and provides a methodological solution that addresses the challenge. Accurate asthma prediction tools can provide early warning and potentially prevent deterioration thereby improving the quality of life of patients with asthma.
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Aprendizaje Automático , Calidad de Vida , Humanos , Algoritmos , Modelos Logísticos , Monitoreo FisiológicoRESUMEN
BACKGROUND: Epidemiological and experimental evidence suggests that higher folate intake is associated with decreased colorectal cancer (CRC) risk; however, the mechanisms underlying this relationship are not fully understood. Genetic variation that may have a direct or indirect impact on folate metabolism can provide insights into folate's role in CRC. OBJECTIVES: Our aim was to perform a genome-wide interaction analysis to identify genetic variants that may modify the association of folate on CRC risk. METHODS: We applied traditional case-control logistic regression, joint 3-degree of freedom, and a 2-step weighted hypothesis approach to test the interactions of common variants (allele frequency >1%) across the genome and dietary folate, folic acid supplement use, and total folate in relation to risk of CRC in 30,550 cases and 42,336 controls from 51 studies from 3 genetic consortia (CCFR, CORECT, GECCO). RESULTS: Inverse associations of dietary, total folate, and folic acid supplement with CRC were found (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.90, 0.96; and 0.91; 95% CI: 0.89, 0.94 per quartile higher intake, and 0.82 (95% CI: 0.78, 0.88) for users compared with nonusers, respectively). Interactions (P-interaction < 5×10-8) of folic acid supplement and variants in the 3p25.2 locus (in the region of Synapsin II [SYN2]/tissue inhibitor of metalloproteinase 4 [TIMP4]) were found using traditional interaction analysis, with variant rs150924902 (located upstream to SYN2) showing the strongest interaction. In stratified analyses by rs150924902 genotypes, folate supplementation was associated with decreased CRC risk among those carrying the TT genotype (OR: 0.82; 95% CI: 0.79, 0.86) but increased CRC risk among those carrying the TA genotype (OR: 1.63; 95% CI: 1.29, 2.05), suggesting a qualitative interaction (P-interaction = 1.4×10-8). No interactions were observed for dietary and total folate. CONCLUSIONS: Variation in 3p25.2 locus may modify the association of folate supplement with CRC risk. Experimental studies and studies incorporating other relevant omics data are warranted to validate this finding.
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Neoplasias Colorrectales , Ácido Fólico , Humanos , Ácido Fólico/metabolismo , Factores de Riesgo , Neoplasias Colorrectales/genética , Estudios de Casos y Controles , Suplementos DietéticosRESUMEN
BACKGROUND: Diabetes is an established risk factor for colorectal cancer. However, the mechanisms underlying this relationship still require investigation and it is not known if the association is modified by genetic variants. To address these questions, we undertook a genome-wide gene-environment interaction analysis. METHODS: We used data from 3 genetic consortia (CCFR, CORECT, GECCO; 31,318 colorectal cancer cases/41,499 controls) and undertook genome-wide gene-environment interaction analyses with colorectal cancer risk, including interaction tests of genetics(G)xdiabetes (1-degree of freedom; d.f.) and joint testing of Gxdiabetes, G-colorectal cancer association (2-d.f. joint test) and G-diabetes correlation (3-d.f. joint test). RESULTS: Based on the joint tests, we found that the association of diabetes with colorectal cancer risk is modified by loci on chromosomes 8q24.11 (rs3802177, SLC30A8 - ORAA: 1.62, 95% CI: 1.34-1.96; ORAG: 1.41, 95% CI: 1.30-1.54; ORGG: 1.22, 95% CI: 1.13-1.31; p-value3-d.f.: 5.46 × 10-11) and 13q14.13 (rs9526201, LRCH1 - ORGG: 2.11, 95% CI: 1.56-2.83; ORGA: 1.52, 95% CI: 1.38-1.68; ORAA: 1.13, 95% CI: 1.06-1.21; p-value2-d.f.: 7.84 × 10-09). DISCUSSION: These results suggest that variation in genes related to insulin signaling (SLC30A8) and immune function (LRCH1) may modify the association of diabetes with colorectal cancer risk and provide novel insights into the biology underlying the diabetes and colorectal cancer relationship.
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Neoplasias Colorrectales , Diabetes Mellitus , Humanos , Interacción Gen-Ambiente , Predisposición Genética a la Enfermedad , Factores de Riesgo , Diabetes Mellitus/genética , Neoplasias Colorrectales/genética , Polimorfismo de Nucleótido Simple , Estudio de Asociación del Genoma Completo/métodos , Proteínas de Microfilamentos/genéticaRESUMEN
Once an infrequent disease in parts of Asia, the rate of colorectal cancer in recent decades appears to be steadily increasing. Colorectal cancer represents one of the most important causes of cancer mortality worldwide, including in many regions in Asia. Rapid changes in socioeconomic and lifestyle habits have been attributed to the notable increase in the incidence of colorectal cancers in many Asian countries. Through published data from the International Agency for Cancer Research (IARC), we utilized available continuous data to determine which Asian nations had a rise in colorectal cancer rates. We found that East and South East Asian countries had a significant rise in colorectal cancer rates. Subsequently, we summarized here the known genetics and environmental risk factors for colorectal cancer among populations in this region as well as approaches to screening and early detection that have been considered across various countries in the region.
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Colorectal cancer risk can be impacted by genetic, environmental, and lifestyle factors, including diet and obesity. Gene-environment interactions (G × E) can provide biological insights into the effects of obesity on colorectal cancer risk. Here, we assessed potential genome-wide G × E interactions between body mass index (BMI) and common SNPs for colorectal cancer risk using data from 36,415 colorectal cancer cases and 48,451 controls from three international colorectal cancer consortia (CCFR, CORECT, and GECCO). The G × E tests included the conventional logistic regression using multiplicative terms (one degree of freedom, 1DF test), the two-step EDGE method, and the joint 3DF test, each of which is powerful for detecting G × E interactions under specific conditions. BMI was associated with higher colorectal cancer risk. The two-step approach revealed a statistically significant G×BMI interaction located within the Formin 1/Gremlin 1 (FMN1/GREM1) gene region (rs58349661). This SNP was also identified by the 3DF test, with a suggestive statistical significance in the 1DF test. Among participants with the CC genotype of rs58349661, overweight and obesity categories were associated with higher colorectal cancer risk, whereas null associations were observed across BMI categories in those with the TT genotype. Using data from three large international consortia, this study discovered a locus in the FMN1/GREM1 gene region that interacts with BMI on the association with colorectal cancer risk. Further studies should examine the potential mechanisms through which this locus modifies the etiologic link between obesity and colorectal cancer. SIGNIFICANCE: This gene-environment interaction analysis revealed a genetic locus in FMN1/GREM1 that interacts with body mass index in colorectal cancer risk, suggesting potential implications for precision prevention strategies.
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Neoplasias Colorrectales , Obesidad , Humanos , Índice de Masa Corporal , Factores de Riesgo , Obesidad/complicaciones , Obesidad/genética , Sitios Genéticos , Neoplasias Colorrectales/genética , Polimorfismo de Nucleótido Simple , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Péptidos y Proteínas de Señalización Intercelular/genéticaRESUMEN
BACKGROUND: Tobacco smoking is an established risk factor for colorectal cancer. However, genetically defined population subgroups may have increased susceptibility to smoking-related effects on colorectal cancer. METHODS: A genome-wide interaction scan was performed including 33,756 colorectal cancer cases and 44,346 controls from three genetic consortia. RESULTS: Evidence of an interaction was observed between smoking status (ever vs. never smokers) and a locus on 3p12.1 (rs9880919, P = 4.58 × 10-8), with higher associated risk in subjects carrying the GG genotype [OR, 1.25; 95% confidence interval (CI), 1.20-1.30] compared with the other genotypes (OR <1.17 for GA and AA). Among ever smokers, we observed interactions between smoking intensity (increase in 10 cigarettes smoked per day) and two loci on 6p21.33 (rs4151657, P = 1.72 × 10-8) and 8q24.23 (rs7005722, P = 2.88 × 10-8). Subjects carrying the rs4151657 TT genotype showed higher risk (OR, 1.12; 95% CI, 1.09-1.16) compared with the other genotypes (OR <1.06 for TC and CC). Similarly, higher risk was observed among subjects carrying the rs7005722 AA genotype (OR, 1.17; 95% CI, 1.07-1.28) compared with the other genotypes (OR <1.13 for AC and CC). Functional annotation revealed that SNPs in 3p12.1 and 6p21.33 loci were located in regulatory regions, and were associated with expression levels of nearby genes. Genetic models predicting gene expression revealed that smoking parameters were associated with lower colorectal cancer risk with higher expression levels of CADM2 (3p12.1) and ATF6B (6p21.33). CONCLUSIONS: Our study identified novel genetic loci that may modulate the risk for colorectal cancer of smoking status and intensity, linked to tumor suppression and immune response. IMPACT: These findings can guide potential prevention treatments.
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Neoplasias Colorrectales , Predisposición Genética a la Enfermedad , Humanos , Neoplasias Colorrectales/epidemiología , Fumar/genética , Factores de Riesgo , Genotipo , Inflamación , Fumar Tabaco , Sitios Genéticos , Polimorfismo de Nucleótido Simple , Estudios de Casos y ControlesRESUMEN
BACKGROUND: An early warning tool to predict attacks could enhance asthma management and reduce the likelihood of serious consequences. Electronic health records (EHRs) providing access to historical data about patients with asthma coupled with machine learning (ML) provide an opportunity to develop such a tool. Several studies have developed ML-based tools to predict asthma attacks. OBJECTIVE: This study aims to critically evaluate ML-based models derived using EHRs for the prediction of asthma attacks. METHODS: We systematically searched PubMed and Scopus (the search period was between January 1, 2012, and January 31, 2023) for papers meeting the following inclusion criteria: (1) used EHR data as the main data source, (2) used asthma attack as the outcome, and (3) compared ML-based prediction models' performance. We excluded non-English papers and nonresearch papers, such as commentary and systematic review papers. In addition, we also excluded papers that did not provide any details about the respective ML approach and its result, including protocol papers. The selected studies were then summarized across multiple dimensions including data preprocessing methods, ML algorithms, model validation, model explainability, and model implementation. RESULTS: Overall, 17 papers were included at the end of the selection process. There was considerable heterogeneity in how asthma attacks were defined. Of the 17 studies, 8 (47%) studies used routinely collected data both from primary care and secondary care practices together. Extreme imbalanced data was a notable issue in most studies (13/17, 76%), but only 38% (5/13) of them explicitly dealt with it in their data preprocessing pipeline. The gradient boosting-based method was the best ML method in 59% (10/17) of the studies. Of the 17 studies, 14 (82%) studies used a model explanation method to identify the most important predictors. None of the studies followed the standard reporting guidelines, and none were prospectively validated. CONCLUSIONS: Our review indicates that this research field is still underdeveloped, given the limited body of evidence, heterogeneity of methods, lack of external validation, and suboptimally reported models. We highlighted several technical challenges (class imbalance, external validation, model explanation, and adherence to reporting guidelines to aid reproducibility) that need to be addressed to make progress toward clinical adoption.
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OBJECTIVES: Genome-wide association studies (GWAS) are performed to study the associations between genetic variants with respect to certain phenotypic traits such as cancer. However, the method that is commonly used in GWAS assumes that certain traits are solely affected by a single mutation. We propose a network analysis method, in which we generate association networks of single-nucleotide polymorphisms (SNPs) that can differentiate case and control groups. We hypothesize that certain phenotypic traits are attributable to mutations in groups of associated SNPs. METHODS: We propose a method based on a network analysis framework to study SNP-SNP interactions related to cancer incidence. We employed logistic regression to measure the significance of all SNP pairs from GWAS for the incidence of colorectal cancer and computed a cancer risk score based on the generated SNP networks. RESULTS: We demonstrated our method in a dataset from a case-control study of colorectal cancer in the South Sulawesi population. From the GWAS results, 20,094 pairs of 200 SNPs were created. We obtained one cluster containing four pairs of five SNPs that passed the filtering threshold based on their p-values. A locus on chromosome 12 (12:54410007) was found to be strongly connected to the four variants on chromosome 1. A polygenic risk score was computed from the five SNPs, and a significant difference in colorectal cancer risk was obtained between the case and control groups. CONCLUSIONS: Our results demonstrate the applicability of our method to understand SNP-SNP interactions and compute risk scores for various types of cancer.
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As the fourth most populous country in the world, Indonesia must increase the annual rice production rate to achieve national food security by 2050. One possible solution comes from the nanoscopic level: a genetic variant called Single Nucleotide Polymorphism (SNP), which can express significant yield-associated genes. The prior benchmark of this study utilized a statistical genetics model where no SNP position information and attention mechanism were involved. Hence, we developed a novel deep polygenic neural network, named the NucleoNet model, to address these obstacles. The NucleoNets were constructed with the combination of prominent components that include positional SNP encoding, the context vector, wide models, Elastic Net, and Shannon's entropy loss. This polygenic modeling obtained up to 2.779 of Mean Squared Error (MSE) with 47.156% of Symmetric Mean Absolute Percentage Error (SMAPE), while revealing 15 new important SNPs. Furthermore, the NucleoNets reduced the MSE score up to 32.28% compared to the Ordinary Least Squares (OLS) model. Through the ablation study, we learned that the combination of Xavier distribution for weights initialization and Normal distribution for biases initialization sparked more various important SNPs throughout 12 chromosomes. Our findings confirmed that the NucleoNet model was successfully outperformed the OLS model and identified important SNPs to Indonesian rice yields.
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Oryza , Estudio de Asociación del Genoma Completo , Indonesia , Herencia Multifactorial , Redes Neurales de la Computación , Oryza/genética , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: The use of menopausal hormone therapy (MHT) may interact with genetic variants to influence colorectal cancer (CRC) risk. METHODS: We conducted a genome-wide, gene-environment interaction between single nucleotide polymorphisms and the use of any MHT, estrogen only, and combined estrogen-progestogen therapy with CRC risk, among 28â486 postmenopausal women (11â519 CRC patients and 16â967 participants without CRC) from 38 studies, using logistic regression, 2-step method, and 2- or 3-degree-of-freedom joint test. A set-based score test was applied for rare genetic variants. RESULTS: The use of any MHT, estrogen only and estrogen-progestogen were associated with a reduced CRC risk (odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.64 to 0.78; OR = 0.65, 95% CI = 0.53 to 0.79; and OR = 0.73, 95% CI = 0.59 to 0.90, respectively). The 2-step method identified a statistically significant interaction between a GRIN2B variant rs117868593 and MHT use, whereby MHT-associated CRC risk was statistically significantly reduced in women with the GG genotype (OR = 0.68, 95% CI = 0.64 to 0.72) but not within strata of GC or CC genotypes. A statistically significant interaction between a DCBLD1 intronic variant at 6q22.1 (rs10782186) and MHT use was identified by the 2-degree-of-freedom joint test. The MHT-associated CRC risk was reduced with increasing number of rs10782186-C alleles, showing odds ratios of 0.78 (95% CI = 0.70 to 0.87) for TT, 0.68 (95% CI = 0.63 to 0.73) for TC, and 0.66 (95% CI = 0.60 to 0.74) for CC genotypes. In addition, 5 genes in rare variant analysis showed suggestive interactions with MHT (2-sided P < 1.2 × 10-4). CONCLUSION: Genetic variants that modify the association between MHT and CRC risk were identified, offering new insights into pathways of CRC carcinogenesis and potential mechanisms involved.
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Neoplasias Colorrectales , Progestinas , Estudios de Casos y Controles , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/genética , Estrógenos , Femenino , Humanos , Menopausia , Polimorfismo de Nucleótido Simple , Factores de RiesgoRESUMEN
BACKGROUND: Currently known associations between common genetic variants and colorectal cancer explain less than half of its heritability of 25%. As alcohol consumption has a J-shape association with colorectal cancer risk, nondrinking and heavy drinking are both risk factors for colorectal cancer. METHODS: Individual-level data was pooled from the Colon Cancer Family Registry, Colorectal Transdisciplinary Study, and Genetics and Epidemiology of Colorectal Cancer Consortium to compare nondrinkers (≤1 g/day) and heavy drinkers (>28 g/day) with light-to-moderate drinkers (1-28 g/day) in GxE analyses. To improve power, we implemented joint 2df and 3df tests and a novel two-step method that modifies the weighted hypothesis testing framework. We prioritized putative causal variants by predicting allelic effects using support vector machine models. RESULTS: For nondrinking as compared with light-to-moderate drinking, the hybrid two-step approach identified 13 significant SNPs with pairwise r2 > 0.9 in the 10q24.2/COX15 region. When stratified by alcohol intake, the A allele of lead SNP rs2300985 has a dose-response increase in risk of colorectal cancer as compared with the G allele in light-to-moderate drinkers [OR for GA genotype = 1.11; 95% confidence interval (CI), 1.06-1.17; OR for AA genotype = 1.22; 95% CI, 1.14-1.31], but not in nondrinkers or heavy drinkers. Among the correlated candidate SNPs in the 10q24.2/COX15 region, rs1318920 was predicted to disrupt an HNF4 transcription factor binding motif. CONCLUSIONS: Our study suggests that the association with colorectal cancer in 10q24.2/COX15 observed in genome-wide association study is strongest in nondrinkers. We also identified rs1318920 as the putative causal regulatory variant for the region. IMPACT: The study identifies multifaceted evidence of a possible functional effect for rs1318920.
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Neoplasias Colorrectales , Estudio de Asociación del Genoma Completo , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/epidemiología , Consumo de Bebidas Alcohólicas/genética , Neoplasias Colorrectales/etiología , Neoplasias Colorrectales/genética , Complejo IV de Transporte de Electrones/genética , Humanos , Polimorfismo de Nucleótido Simple , Factores de RiesgoRESUMEN
Genome-wide association (GWA) genetic epidemiology research has identified several variants modestly associated with brief self-report smoking measures, predominately in European Americans. GWA research has not applied intensive laboratory-based measures of smoking endophenotypes in African Americans-a population with disproportionately low quit smoking rates and high tobacco-related disease risk. This genetic epidemiology study of non-Hispanic African Americans tested associations of 89 genetic variants identified in previous GWA research and exploratory GWAs with 24 laboratory-derived tobacco withdrawal endophenotypes. African American cigarette smokers (N = 528; ≥10 cig/day; 36.2% female) completed two counterbalanced visits following either 16-hr of tobacco deprivation or ad libitum smoking. At both visits, self-report and behavioral measures across six unique "sub-phenotype" domains within the tobacco withdrawal syndrome were assessed (Urge/Craving, Negative Affect, Low Positive Affect, Cognition, Hunger, and Motivation to Resume Smoking). Results of the candidate variant analysis found two significant small-magnitude associations. The rs11915747 alternate allele in the CAD2M gene region was associated with .09 larger deprivation-induced changes in reported impulsivity (0-4 scale). The rs2471711alternate allele in the AC097480.1/AC097480.2 gene region was associated with 0.26 lower deprivation-induced changes in confusion (0-4 scale). For both variants, associations were opposite in direction to previous research. Individual genetic variants may exert only weak influences on tobacco withdrawal in African Americans. Larger sample sizes of non-European ancestry individuals might be needed to investigate both known and novel loci that may be ancestry-specific. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
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Negro o Afroamericano , Cese del Hábito de Fumar , Negro o Afroamericano/genética , Endofenotipos , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Cese del Hábito de Fumar/métodos , NicotianaRESUMEN
OBJECTIVE: Several studies have recently indicated a huge shifting pattern toward early age onset cases in breast cancer (BC) patients. However, the studies exerted relatively limited to the Caucasian population. This preliminary study is aimed to investigate the genetic risk factors for young BC patients specifically in Indonesia population. METHODS: DNA samples were extracted from 79 BC patients aged younger than 40 years old and 90 healthy samples. These DNA samples were sequenced using Illumina NextSeq 500 platform and preprocessed to extract the single-nucleotide polymorphisms (SNPs) data. Firstly, multiple univariate logistic regressions were performed to test the association between each SNP and BC incidence in young patients. Furthermore, to analyze the polygenic effects derived from multiple SNPs, we employed a multivariate logistics regression. RESULTS: There were only 15 SNPs passed our 95% call rate threshold thus subsequently were used in the association test. One of these variants, rs3219493, emerged to be significantly associated with early-onset BC (p-value = 0.025, OR = 3.750, 95% CI = 1.178-11.938). This result is consistent with the multivariate logistic regression model, where the pertinent variant was found statistically significant (p-value = 0.008, OR = 8.398, 95% CI = 1.720-40.920). This variant was identified as an intronic variant within MUTYH gene which has been reported in several published studies to exhibit an association with the incidence of breast cancer in China, Italy and Sephardi Jews population. However, there is no evident this gene impacting the risk of developing early onset of BC in Indonesia population. CONCLUSION: Despite our limitation in terms of sample size analyzed in this preliminary study, our finding on significant association of intronic MUTHY with the early onset of BC in Indonesia led to a broadened insight of population-based unique aspect to being taken into an in-depth account for and advancement of chemotherapy.
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Pueblo Asiatico/genética , Neoplasias de la Mama/genética , ADN Glicosilasas/genética , Predisposición Genética a la Enfermedad/genética , Adulto , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/etnología , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad/epidemiología , Predisposición Genética a la Enfermedad/etnología , Humanos , Incidencia , Indonesia/epidemiología , Modelos Logísticos , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: Several reports on the discovery of SARS-CoV-2 mutations and variations in Indonesia COVID-19 cases led to genomic dysregulation with the first pandemic cases in Wuhan, China. MicroRNA (miRNA) plays an important role in this genetic regulation and contributes to the enhancement of viral RNA binding through the host mRNA. OBJECTIVE: This research is aimed to detect miRNA targets of SARS-CoV-2 and examines their role in Indonesia cases against Wuhan cases. METHODS: SARS-CoV-2 sequences were obtained from GISAID ( https://www.gisaid.org/ ), NCBI ( https://ncbi.nlm.nih.gov ), and National Genomics Data Center ( https://bigd.big.ac.cn/gwh/ ) databases. MiRDB ( https://github.com/gbnegrini/mirdb-custom-target-search ) was used to annotate and predict target human mature miRNAs. For statistical analysis, we utilized a series chi-square test to obtain significant miRNA. DIANA-miRPath v3.0 ( http://www.microrna.gr/miRPathv3 ) analyzed the Gene Ontology of mature miRNAs. RESULT: The statistical results detected five significant miRNAs. Two miRNAs: hsa-miR-4778-5p and hsa-miR-4531 were consistently found in the majority of Wuhan samples, while they were only found in less than half of the Indonesia samples. The other three miRNA, hsa-miR-6844, hsa-miR-627-5p, and hsa-miR-3674, were discovered in most samples in both groups but with a significant difference ratio. Among these five significant miRNA targets, hsa-miR-6844 is the only miRNA that has an association with the ORF1ab gene of SARS-CoV-2. CONCLUSION: The Gene Ontology analysis of five significant miRNA targets indicates a significant role in inflammation and the immune system. The specific detection of host miRNAs in this study shows that there are differences in the characteristics of SARS-CoV-2 between Indonesia and Wuhan.
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COVID-19/genética , MicroARNs/genética , SARS-CoV-2/genética , COVID-19/epidemiología , COVID-19/virología , China , Humanos , Indonesia , SARS-CoV-2/patogenicidad , Homología de Secuencia de Ácido NucleicoRESUMEN
Colorectal cancer is a common cancer in Indonesia, yet it has been understudied in this resource-constrained setting. We conducted a genome-wide association study focused on evaluation and preliminary discovery of colorectal cancer risk factors in Indonesians. We administered detailed questionnaires and collecting blood samples from 162 colorectal cancer cases throughout Makassar, Indonesia. We also established a control set of 193 healthy individuals frequency matched by age, sex, and ethnicity. A genome-wide association analysis was performed on 84 cases and 89 controls passing quality control. We evaluated known colorectal cancer genetic variants using logistic regression and established a genome-wide polygenic risk model using a Bayesian variable selection technique. We replicate associations for rs9497673, rs6936461 and rs7758229 on chromosome 6; rs11255841 on chromosome 10; and rs4779584, rs11632715, and rs73376930 on chromosome 15. Polygenic modeling identified 10 SNP associated with colorectal cancer risk. This work helps characterize the relationship between variants in the SCL22A3, SCG5, GREM1, and STXBP5-AS1 genes and colorectal cancer in a diverse Indonesian population. With further biobanking and international research collaborations, variants specific to colorectal cancer risk in Indonesians will be identified.
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Neoplasias Colorrectales/etnología , Neoplasias Colorrectales/genética , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Indonesia/epidemiología , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
Reports from various population-based studies indicate that the incidence of colorectal cancer may be strongly affected by dietary patterns of the respective populations. The nature of dietary patterns of specific Indonesia population on the risk of colorectal cancer might differ from previously published data with the global population. Therefore, we conducted a study where the dietary pattern in colorectal cancer patient cohorts was compared to age- and population-matched control. We documented 89 colorectal cancer cases and among 173 individuals from the South Sulawesi population. A series of logistic regression and Fisher's exact tests were utilized to test associations of dietary intakes and colorectal cancer risk as well as colorectal cancer staging. Our data demonstrate that vegetable (p-value = 8.70 × 10-26, OR = 0.49) and fruit (p-value = 7.59x10-5, OR = 0.70) intakes are associated with the reduced risk of colorectal cancer incidence. Conversely, acidic food, reheated food, meat, spicy food, and alcohol are associated with the increment case of cancer. Moreover, meat intake (p-value < 0.01) shows a significant association with cancer staging progression. Common dietary pattern is a determinant aspect to the colorectal cancer incidence as well as its staging progression.
Asunto(s)
Neoplasias Colorrectales , Estudios de Casos y Controles , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/etiología , Dieta , Ingestión de Alimentos , Humanos , Incidencia , Indonesia/epidemiología , Factores de RiesgoRESUMEN
OBJECTIVES: Recently, wearable device technology has gained more popularity in supporting a healthy lifestyle. Hence, researchers have begun to put significant efforts into studying the direct and indirect benefits of wearable devices for health and wellbeing. This paper summarizes recent studies on the use of consumer wearable devices to improve physical activity, mental health, and health consciousness. METHODS: A thorough literature search was performed from several reputable databases, such as PubMed, Scopus, ScienceDirect, arXiv, and bioRxiv mainly using "wearable device research" as a keyword, no earlier than 2018. As a result, 25 of the most recent and relevant papers included in this review cover several topics, such as previous literature reviews (9 papers), wearable device accuracy (3 papers), self-reported data collection tools (3 papers), and wearable device intervention (10 papers). RESULTS: All the chosen studies are discussed based on the wearable device used, complementary data, study design, and data processing method. All these previous studies indicate that wearable devices are used either to validate their benefits for general wellbeing or for more serious medical contexts, such as cardiovascular disorders and post-stroke treatment. CONCLUSIONS: Despite their huge potential for adoption in clinical settings, wearable device accuracy and validity remain the key challenge to be met. Some lessons learned and future projections, such as combining traditional study design with statistical and machine learning methods, are highlighted in this paper to provide a useful overview for other researchers carrying out similar research.
RESUMEN
The aim of this study is to assess the viscoelastic parameters (i.e., phase angle and dynamic modulus) of asphalt concrete-wearing course (AC-WC) and hot rolled sheet-wearing course (HRS-WC) mixtures obtained from the dynamic modulus test. This study was accomplished in four stages: determining optimum asphalt content using Marshall mix design procedure, stability and flow parameters from Marshall test, viscoelastic parameters from dynamic modulus testing and finally the generation of dynamic modulus master curves at a reference temperature of 25 °C. The results showed that at the same temperature, the dynamic modulus of AC-WC and HRS-WC mixtures tended to increase with escalating the loading frequency, while dynamic modulus decreases with an increase in the test temperature at constant loading frequency. Furthermore, the dynamic modulus of the AC-WC mixture was recorded as 100% higher than the HRS-WC asphalt mixture. The phase angle, however, showed contradictory behavior with that shown in dynamic modulus. The phase angle of the AC-WC mixture and HRS-WC asphalt mixture showed almost the same behavior. Similarly, the dynamic modulus master curves of AC-WC and HRS-WC asphalt mixtures can be used to predict the dynamic modulus at the frequency range of 0.01 to 10 Hz and a reference temperature of 25 °C. The results were also used to evaluate the rutting and fatigue performance of AC-WC and HRS-WC.