A genetic risk score and diabetes predict development of alcohol-related cirrhosis in drinkers.

BACKGROUND & AIMS: Only a minority of excess alcohol drinkers develop cirrhosis. We developed and evaluated risk stratification scores to identify those at highest risk. METHODS: Three cohorts (GenomALC-1: n = 1,690, GenomALC-2: n = 3,037, UK Biobank: relevant n = 6,898) with a history of heavy alcohol consumption (≥80 g/day (men), ≥50 g/day (women), for ≥10 years) were included. Cases were participants with alcohol-related cirrhosis. Controls had a history of similar alcohol consumption but no evidence of liver disease. Risk scores were computed from up to 8 genetic loci identified previously as associated with alcohol-related cirrhosis and 3 clinical risk factors. Score performance for the stratification of alcohol-related cirrhosis risk was assessed and compared across the alcohol-related liver disease spectrum, including hepatocellular carcinoma (HCC). RESULTS: A combination of 3 single nucleotide polymorphisms (SNPs) (PNPLA3:rs738409, SUGP1-TM6SF2:rs10401969, HSD17B13:rs6834314) and diabetes status best discriminated cirrhosis risk. The odds ratios (ORs) and (95% CIs) between the lowest (Q1) and highest (Q5) score quintiles of the 3-SNP score, based on independent allelic effect size estimates, were 5.99 (4.18-8.60) (GenomALC-1), 2.81 (2.03-3.89) (GenomALC-2), and 3.10 (2.32-4.14) (UK Biobank). Patients with diabetes and high risk scores had ORs of 14.7 (7.69-28.1) (GenomALC-1) and 17.1 (11.3-25.7) (UK Biobank) compared to those without diabetes and with low risk scores. Patients with cirrhosis and HCC had significantly higher mean risk scores than patients with cirrhosis alone (0.76 ± 0.06 vs. 0.61 ± 0.02, p = 0.007). Score performance was not significantly enhanced by information on additional genetic risk variants, body mass index or coffee consumption. CONCLUSIONS: A risk score based on 3 genetic risk variants and diabetes status enables the stratification of heavy drinkers based on their risk of cirrhosis, allowing for the provision of earlier preventative interventions. LAY SUMMARY: Excessive chronic drinking leads to cirrhosis in some people, but so far there is no way to identify those at high risk of developing this debilitating disease. We developed a genetic risk score that can identify patients at high risk. The risk of cirrhosis is increased >10-fold with just two risk factors - diabetes and a high genetic risk score. Risk assessment using this test could enable the early and personalised management of this disease in high-risk patients.

Refinement of pathogenicity classification of variants associated with familial hypercholesterolemia: Implications for clinical diagnosis.

BACKGROUND: The lack of functional evidence for most variants detected during the molecular screening of patients with clinical familial hypercholesterolemia (FH) makes the definitive diagnosis difficult. METHODS: A total of 552 variants in LDLR, APOB, PCSK9 and LDLRAP1 genes found in 449 mutation-positive FH (FH/M+) patients were considered. Pathogenicity update was performed following the American College of Medical Genetics and Genomics (ACMG) guidelines with additional specifications on copy number variants, functional studies, in silico prediction and co-segregation criteria for LDLR, APOB and PCSK9 genes. Pathogenicity of LDLRAP1 variants was updated by using ACMG criteria with no change to original scoring. RESULTS: After reclassification, the proportion of FH/M+ carriers of pathogenic (P) or likely pathogenic (LP) variants, and FH/M+ carriers of likely benign (LB) or benign (B) variants, was higher than that defined by standard criteria (81.5% vs. 79.7% and 7.1% vs. 2.7%). The refinement of pathogenicity classification also reduced the percentage of FH with variants of uncertain significance (VUS) (17.7% vs. 11.4%). After adjustment, the FH diagnosis by refined criteria best predicted LDL-C levels (Padj <0.001). Notably, FH with VUS variants had higher LDL-C than those with LB (all Padj ≤ 0.033), but similar to those with LP variants. CONCLUSION: Accurate variant interpretation best predicts the increase of LDL-C levels and shows its clinical utility in the molecular diagnosis of FH.

Distribución espacial del seguimiento de cáncer de mama en un área rural de la estrategia de salud familiar / Spatial distribution of breast cancer tracking in a rural area of the family health strategy / Distribuição espacial do rastreamento do câncer de mama em uma área rural da estratégia de saúde da familia

OBJETIVO: Demostrar mediante georreferenciación micro áreas con debilidades en el cribado del cáncer de mama en el área de Family Strategy Caxirimbu, área rural de Caxias, Maranhão, Brasil. MÉTODOS: Investigación epidemiológica seccional. Se entrevistó a 211 mujeres, con edades entre 40 y 69 años, entre el 1 de abril y el 1 de septiembre de 2015. La técnica de georreferenciación se utilizó con la producción de coordenadas geográficas utilizando equipos GPS y la producción de mapas de distribución espacial. RESULTADOS: En la distribución espacial, se encontró que el cribado del cáncer de mama en el área de Caxirimbu tiene un mayor alcance en las micro áreas en los márgenes de MA 034 y en las micro áreas cercanas a la unidad de salud. En esta cobertura, se encontró que de las 211 mujeres entrevistadas, 133 (63.0%) ya se habían sometido a una mamografía, estando cerca del parámetro indicado por el Ministerio de Salud, que es al menos el 70.0%. 42.0% (n = 56) ya se había sometido a una mamografía; 36.0% (n = 48), dos o tres mamografías, y el 22.0% (n = 29) informó haber realizado más de cuatro mamografías. El mapa mostró que 11 lugares de este examen son inaccesibles para las mujeres. En la distribución espacial, hubo una mayor distribución para la mamografía irregular, convergiendo con su frecuencia del 80.0%. CONCLUSIÓN: La distribución espacial de los intervalos practicados por las mujeres para los exámenes de mamografía demostró la mayor parte de la ejecución y la ocurrencia de intervalos inadecuados, identificando la necesidad de implementar una detección organizada

OBJETIVO: Demonstrar por meio do georreferenciamento microáreas com fragilidades no rastreamento do câncer de mama em na área da estratégia de Família do Caxirimbu, zona rural de Caxias - Maranhão. MÉTODOS: Pesquisa epidemiológica do tipo seccional. Foram pesquisadas 211 mulheres de 40 a 69 anos entre 01 de abril a 01 de setembro de 2015. Utilizou-se a técnica do georreferenciamento com produção de coordenadas geográficas por meio de equipamento GPS e produção de mapas de distribuição espacial. RESULTADOS: Na distribuição espacial verificou-se que o rastreamento do câncer de mama na área de abrangência do Caxirimbu tem maior alcance nas microáreas as margens da MA 034 e em microáreas próxima a unidade de saúde. Nesta cobertura, verificou-se que das 211 mulheres entrevistadas, 133 (63,0%) já haviam realizado a mamografia ficando próximo do parâmetro indicado pelo ministério da saúde que é de no mínimo 70,0%. 42,0% (n=56) já haviam realizado 1 mamografia; 36,0% (n=48), 2 a 3 mamografias e; 22,0% (n=29) informou ter realizado mais de 4 mamografias. A execução da mamografia e sua regularidade teve uma frequência de 26,0% e 20,0%, respectivamente. O mapa mostrou que 11 localidades esse rastreamento está inacessível para as mulheres. Verificou-se na distribuição espacial maior distribuição para execução irregular da mamografia convergindo com sua frequência de 80,0%. CONCLUSÃO: A distribuição espacial dos intervalos praticados pelas mulheres para a realização dos exames de mamografia demonstrou que a maioria da execução e ocorrência de intervalos inadequados, identificando a necessidade de implementação de um rastreamento organizado

OBJECTIVE: To demonstrate by means of georeferencing micro-areas with weaknesses in screening of breast cancer in the area of ​​the Caxirimbu Family Strategy, rural zone of Caxias, Maranhão state, Brazil. METHODS: Sectional epidemiological research. A total of 211 women aged 40 to 69 years were surveyed between April 1 and September 1, 2015. The georeferencing technique was used with the production of geographical coordinates using GPS equipment and the production of spatial distribution maps. RESULTS: In the spatial distribution, it was found that breast cancer screening in the area covered by Caxirimbu has greater reach in the micro areas on the margins of MA 034 and in micro areas close to the health unit. In this coverage, it was found that of the 211 women interviewed, 133 (63.0%) had already undergone mammography, being close to the parameter indicated by the Ministry of Health, which is at least 70.0%. 42.0% (n= 56) had already undergone one mammogram; 36.0% (n= 48), two to three mammograms and; 22.0% (n= 29) reported having performed more than four mammograms. The map showed that 11 locations that tracking is inaccessible to women. In the spatial distribution, there was a greater distribution for irregular mammography performance, converging with its frequency of 80.0%. CONCLUSION: The spatial distribution of the intervals practiced by women for mammography exams demonstrated that most of the execution and occurrence of inadequate intervals, identifying the need to implement an organized screening

La puntuación de riesgo poligénico como factor clave en los modelos de predicción clínica cardiovascular / Polygenic risk score as a key factor in cardiovascular clinical prediction models

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Una puntuación de riesgo genético predice recurrencias en pacientes jóvenes con infarto agudo de miocardio / A genetic risk score predicts recurrent events after myocardial infarction in young adults

INTRODUCCIÓN Y OBJETIVOS: Evaluar si una puntuación de riesgo genético (GRS) mejora la predicción de eventos recurrentes en pacientes jóvenes con infarto agudo de miocardio (IAM) e identifica una forma de aterosclerosis más agresiva. MÉTODOS: Se diseñó un estudio prospectivo con pacientes <55 años, no diabéticos, ingresados por IAM. Se realizó un test genético, una tomografía computarizada cardiaca y determinación de varios biomarcadores. Se analizó la asociación de un GRS compuesto por 11 variantes genéticas con la aparición de un objetivo primario combinado (muerte cardiovascular, evento recurrente u hospitalización cardiovascular). RESULTADOS: Se siguió a 81 pacientes durante una mediana de 4,1 años, y se documentaron 24 eventos. La prevalencia de variantes de riesgo fue superior en 9 de los 11 alelos frente a población general. El GRS se asoció con recurrencias, particularmente cuando los niveles basales de colesterol-LDL estaban elevados. En el modelo multivariado, teniendo como referencia el tercil de bajo riesgo genético, el HR para el grupo de riesgo intermedio fue de 10,2 (IC95% 1,1-100,3; p = 0,04) y de alto riesgo 20,7 (2,4-181,0; p = 0,006) si el colesterol-LDL era≥2,8 mmol/l (≥ 110mg/dl). La incorporación del GRS al modelo multivariado mejoró el estadístico C (ΔC-statistic=0,086), el cNRI (30%) y el IDI (0,05). El TC cardiaco detectó ateromatosis calcificada frecuentemente, pero tuvo un valor pronóstico limitado. No se detectó una asociación entre metaloproteinasas, GRS y recurrencias. CONCLUSIONES: En una población de pacientes jóvenes no diabéticos con IAM, una puntuación de riesgo genético puede predecir recurrencias y mejorar los modelos clínicos de estratificación pronóstica, especialmente en aquellos pacientes con colesterol-LDL basal elevado

INTRODUCTION AND OBJECTIVES: To evaluate whether a genetic risk score (GRS) improves prediction of recurrent events in young nondiabetic patients presenting with an acute myocardial infarction (AMI) and identifies a more aggressive form of atherosclerosis. METHODS: We conducted a prospective study with consecutive nondiabetic patients aged <55 years presenting with AMI. We performed a genetic test, cardiac computed tomography, and analyzed several biomarkers. We studied the association of a GRS composed of 11 genetic variants and a primary composite endpoint (cardiovascular mortality, a recurrent event, and cardiac hospitalization). RESULTS: A total of 81 patients were studied and followed up for a median of 4.1 years. There were 24 recurrent cardiovascular events. Compared with the general population, study participants had a higher prevalence of 9 out of 11 risk alleles. The GRS was significantly associated with recurrent cardiovascular events, especially when baseline low-density lipoprotein cholesterol (LDL-C) levels were elevated. Compared with the low-risk GRS tertile, the multivariate-adjusted HR for recurrences was 10.2 (95%CI, 1.1-100.3; P=.04) for the intermediate-risk group and was 20.7 (2.4-181.0; P=.006) for the high-risk group when LDL-C was≥2.8 mmol/L (≥ 110mg/dL). Inclusion of the GRS improved the C-statistic (ΔC-statistic=0.086), cNRI (continuous net reclassification improvement) (30%), and the IDI (integrated discrimination improvement) index (0.05). Cardiac computed tomography frequently detected coronary calcified atherosclerosis but had limited value for prediction of recurrences. No association was observed between metalloproteinases, GRS and recurrences. CONCLUSIONS: A multilocus GRS may identify individuals at increased risk of long-term recurrences among young nondiabetic patients with AMI and improve clinical risk stratification models, particularly among patients with high baseline LDL-C levels

PopPhy-CNN: A Phylogenetic Tree Embedded Architecture for Convolutional Neural Networks to Predict Host Phenotype From Metagenomic Data.

Accurate prediction of the host phenotype from a metagenomic sample and identification of the associated microbial markers are important in understanding potential host-microbiome interactions related to disease initiation and progression. We introduce PopPhy-CNN, a novel convolutional neural network (CNN) learning framework that effectively exploits phylogenetic structure in microbial taxa for host phenotype prediction. Our approach takes an input format of a 2D matrix representing the phylogenetic tree populated with the relative abundance of microbial taxa in a metagenomic sample. This conversion empowers CNNs to explore the spatial relationship of the taxonomic annotations on the tree and their quantitative characteristics in metagenomic data. We show the competitiveness of our model compared to other available methods using nine metagenomic datasets of moderate size for binary classification. With synthetic and biological datasets, we show the superior and robust performance of our model for multi-class classification. Furthermore, we design a novel scheme for feature extraction from the learned CNN models and demonstrate improved performance when the extracted features. PopPhy-CNN is a practical deep learning framework for the prediction of host phenotype with the ability of facilitating the retrieval of predictive microbial taxa.

Patient perspectives on variant reclassification after cancer susceptibility testing.

BACKGROUND: Little is known about the impact of reclassification on patients' perception of medical uncertainty or trust in genetics-based clinical care. METHODS: Semistructured telephone interviews were conducted with 20 patients who had received a reclassified genetic test result related to hereditary cancer. All participants had undergone genetic counseling and testing for cancer susceptibility at Vanderbilt-Ingram Cancer Center Hereditary Cancer Clinic within the last six years. RESULTS: Most of the participants did not express distress related to the variant reclassification and only a minority expressed a decrease in trust in medical genetics. However, recall of the new interpretation was limited, even though all participants were recontacted by letter, phone, or clinic visit. CONCLUSION: Reclassification of genetic tests is an important issue in modern healthcare because changes in interpretation have the potential to alter previously recommended management. Participants in this study did not express strong feelings of mistrust or doubt about their genetic evaluation. However, there was a low level of comprehension and information retention related to the updated report. Future research can build on this study to improve communication with patients about their reclassified results.

Overview of Specifications to the ACMG/AMP Variant Interpretation Guidelines.

The 2015 ACMG/AMP guidelines established a classification system for sequence variants; however, the broad scope of these guidelines necessitates specification of evidence types for specific genes or diseases of interest. Since publication of the guidelines, both general use and disease-focused specifications have emerged to aid in accurate application of ACMG/AMP evidence types. This article summarizes the approaches to, and rationale for, specifying three evidence categories (population frequency data, variant type and location, and case-level data), including available resources and a quantitative framework that can inform the specification process. © 2019 by John Wiley & Sons, Inc.

Genetic Causes of Inner Ear Anomalies: a Review from the Turkish Study Group for Inner Ear Anomalies

Inner ear anomalies diagnosed using a radiological study are detected in almost 30% of cases with congenital or prelingual-onset sensorineural hearing loss. Inner ear anomalies can be isolated or occur along with a part of a syndrome involving other systems. Although astonishing progress has been made in research aimed at revealing the genetic causes of hearing loss in the past few decades, only a few genes have been linked to inner ear anomalies. The aim of this review is to discuss the known genetic causes of inner ear anomalies. Identifying the genetic causes of inner ear anomalies is important for guiding clinical care that includes empowered reproductive decisions provided to the affected individuals. Furthermore, understanding the molecular underpinnings of the development of the inner ear in humans is important to develop novel treatment strategies for people with hearing loss.

Outcomes of 92 patient-driven family studies for reclassification of variants of uncertain significance.

PURPOSE: Family studies are an important but underreported source of information for reclassification of variants of uncertain significance (VUS). We evaluated outcomes of a patient-driven framework that offered familial VUS reclassification analysis to any adult with any clinically ascertained VUS from any laboratory in the United States. METHODS: With guidance from FindMyVariant.org, participants recruited their own relatives for study participation. We genotyped relatives, calculated quantitative cosegregation likelihood ratios, and evaluated variant classifications using Tavtigian's unified framework for Bayesian analysis with American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) criteria. We report participation and VUS reclassification rates from the 50 families enrolled for at least one year and reclassification results for 112 variants from the larger 92-family cohort. RESULTS: For the 50-family cohort, 6.7 relatives per family were invited to participate and 67% of relatives returned samples for genotyping. Sixty-one percent of VUS were reclassified, 84% of which were classified as benign or likely benign. Genotyping relatives identified a de novo variant, phase variants, and relatives with phenotypes highly specific for or incompatible with specific classifications. CONCLUSIONS: Motivated families can contribute to successful VUS reclassification at substantially higher rates than those previously published. Clinical laboratories could consider offering family studies to all patients with VUS.

Accurate classification of BRCA1 variants with saturation genome editing.

Variants of uncertain significance fundamentally limit the clinical utility of genetic information. The challenge they pose is epitomized by BRCA1, a tumour suppressor gene in which germline loss-of-function variants predispose women to breast and ovarian cancer. Although BRCA1 has been sequenced in millions of women, the risk associated with most newly observed variants cannot be definitively assigned. Here we use saturation genome editing to assay 96.5% of all possible single-nucleotide variants (SNVs) in 13 exons that encode functionally critical domains of BRCA1. Functional effects for nearly 4,000 SNVs are bimodally distributed and almost perfectly concordant with established assessments of pathogenicity. Over 400 non-functional missense SNVs are identified, as well as around 300 SNVs that disrupt expression. We predict that these results will be immediately useful for the clinical interpretation of BRCA1 variants, and that this approach can be extended to overcome the challenge of variants of uncertain significance in additional clinically actionable genes.

Cardiovascular Clearance for Sports Participation.

Sudden cardiac death (SCD) in a young athlete is a rare but tragic occurrence. The goal of this article is to provide information about the risks of sudden cardiac death in athletes by reviewing the epidemiology and describing the current screening recommendations of the American Heart Association/American College of Cardiology. 1 The specifics of and reasons for differences between screening guidelines in the United States and the screening guidelines in Europe are highlighted. Electrocardiogram (ECG) changes that can be expected in the setting of conditioning vs pathology are described. Intrinsic cardiac pathologies and disorders, with related cardiac findings, are reviewed, including prevalence and inheritance patterns. Also included is a brief medical-legal discussion about physician liability in the course of making sports clearance decisions. In an area in which there is no single national standard but in which there is an expectation by almost all states for a clearance examination, this article aims to help physicians make thoughtful decisions when evaluating a seemingly healthy patient in order to detect those rare athletes who may be at increased risk of succumbing to a sudden cardiac death during sports participation. 21.

The Genomic Health of Ancient Hominins.

The genomes of ancient humans, Neandertals, and Denisovans contain many alleles that influence disease risks. Using genotypes at 3,180 disease-associated loci, we estimated the disease burden of 147 ancient genomes. After correcting for missing data, genetic risk scores (GRS) were generated for nine disease categories and the set of all combined diseases. We used these genetic risk scores to examine the effects of different types of subsistence, geography, and sample age on the number of risk alleles in each ancient genome. On a broad scale, hereditary disease risks are similar for ancient hominins and modern-day humans, and the GRS percentiles of ancient individuals span the full range of what is observed in present-day individuals. In addition, there is evidence that ancient pastoralists may have had healthier genomes than hunter-gatherers and agriculturalists. We also observed a temporal trend whereby genomes from the recent past are more likely to be healthier than genomes from the deep past. This calls into question the idea that modern lifestyles have caused genetic load to increase over time. Focusing on individual genomes, we found that the overall genomic health of the Altai Neandertal is worse than 97% of present-day humans and that Ötzi, the Tyrolean Iceman, had a genetic predisposition for gastrointestinal and cardiovascular diseases. As demonstrated by this work, ancient genomes afford us new opportunities to diagnose past human health, which has previously been limited by the quality and completeness of remains.

Gene2DisCo: Gene to disease using disease commonalities.

OBJECTIVE: Finding the human genes co-causing complex diseases, also known as "disease-genes", is one of the emerging and challenging tasks in biomedicine. This process, termed gene prioritization (GP), is characterized by a scarcity of known disease-genes for most diseases, and by a vast amount of heterogeneous data, usually encoded into networks describing different types of functional relationships between genes. In addition, different diseases may share common profiles (e.g. genetic or therapeutic profiles), and exploiting disease commonalities may significantly enhance the performance of GP methods. This work aims to provide a systematic comparison of several disease similarity measures, and to embed disease similarities and heterogeneous data into a flexible framework for gene prioritization which specifically handles the lack of known disease-genes. METHODS: We present a novel network-based method, Gene2DisCo, based on generalized linear models (GLMs) to effectively prioritize genes by exploiting data regarding disease-genes, gene interaction networks and disease similarities. The scarcity of disease-genes is addressed by applying an efficient negative selection procedure, together with imbalance-aware GLMs. Gene2DisCo is a flexible framework, in the sense it is not dependent upon specific types of data, and/or upon specific disease ontologies. RESULTS: On a benchmark dataset composed of nine human networks and 708 medical subject headings (MeSH) diseases, Gene2DisCo largely outperformed the best benchmark algorithm, kernelized score functions, in terms of both area under the ROC curve (0.94 against 0.86) and precision at given recall levels (for recall levels from 0.1 to 1 with steps 0.1). Furthermore, we enriched and extended the benchmark data to the whole human genome and provided the top-ranked unannotated candidate genes even for MeSH disease terms without known annotations.

The MOGE(S) classification for cardiomyopathies: current status and future outlook.

Cardiomyopathies are complex diseases of multifactorial pathogenesis and have a high morbidity and mortality. Over the past decades, several revisions of classifications and definitions of cardiomyopathies have been proposed, primarily focusing on the phenotypic characterization of cardiomyopathies. The MOGE(S) classification system published in 2013 encompasses the classification of rapidly growing knowledge on genetic mutations, acquired causes (i.e., intramyocardial inflammation, viral infections), and further conditions involved in the induction of cardiomyopathies (e.g., storage diseases, toxicity). It is based on five attributes, including morphofunctional characteristics (M), organ involvement (O), genetic or familial inheritance pattern (G), etiological annotation (E), and optional information about the heart failure functional status (S). This review summarizes the development, the cornerstones of the MOGE(S) classification, and the published data on the clinical relevance of the MOGE(S) classification. We furthermore discuss new issues which might be considered for future updates of the MOGE(S) classification of cardiomyopathies.

Evaluation of a community-based hypertension improvement program (ComHIP) in Ghana: data from a baseline survey.

BACKGROUND: Ghana faces an increasing burden of non-communicable disease with rates of hypertension estimated as high as 36% in adults. Despite these high rates, hypertension control remains very poor in Ghana (4%). The current project aims to implement and evaluate a community-based programme to raise awareness, and to improve treatment and control of hypertension in the Eastern Region of Ghana. In this paper, we present the findings of the baseline cross-sectional survey focusing on hypertension prevalence, awareness, treatment, and control. METHODS: To evaluate the ComHIP project, a quasi-experimental design consisted of a before and after evaluations are being implemented in the intervention and comparison districts. A cohort study component is being implemented in the intervention district to assess hypertension control. Background anthropometric and clinical data collected as part of the baseline survey were analyzed in STATA Version 11. We examined the characteristics of individuals, associated with the baseline study outcomes using logistic regression models. RESULTS: We interviewed 2400 respondents (1200 each from the comparison and intervention districts), although final sample sizes after data cleaning were 1170 participants in the comparison district and 1167 in the intervention district. With the exception of ethnicity, the control and intervention districts compare favorably. Overall 32.4% of the study respondents were hypertensive (31.4% in the control site; and 33.4% in the intervention site); 46.2% of hypertensive individuals were aware of a previous diagnosis of hypertension (44.7% in the control site, and 47.7% in the intervention site), and only around 9% of these were being treated in either arm. Hypertension control was 1.3% overall (0.5% in the comparison site, and 2.1% in the intervention site). Age was a predictor of having hypertension, and so was increasing body mass index (BMI), waist, and hip circumferences. After adjusting for age, the risk factors with the greatest association with hypertension were being overweight (aOR = 2.30; 95% CI 1.53-3.46) or obese (aOR = 3.61; 95% CI 2.37-5.51). Older individuals were more likely to be aware of their hypertension status than younger people. After adjusting for age people with a family history of hypertension or CVD, or having an unhealthy waist hip ratio, were more likely to be aware of their hypertension status. CONCLUSIONS: The high burden of hypertension among the studied population, coupled with high awareness, yet very low level of hypertension treatment and control requires in-depth investigation of the bottlenecks to treatment and control. The low hypertension treatment and control rates despite current and previous general educational programs particularly in the intervention district, may suggest that such programs are not necessarily impactful on the health of the population.

Associations Between Type 2 Diabetes-Related Genetic Scores and Metabolic Traits, in Obese and Normal-Weight Youths.

CONTEXT: Young-onset obesity is strongly associated with the early development of type 2 diabetes (T2D). Genetic risk scores (GRSs) related to T2D might help predicting the early impairment of glucose homeostasis in obese youths. OBJECTIVE: Our objective was to investigate the contributions of four GRSs (associated with: T2D [GRS-T2D], beta-cell function [GRS-ß], insulin resistance [GRS-IR], and body mass index) to the variation of traits derived from oral glucose tolerance test (OGTT) in obese and normal-weight children and young adults. DESIGN: This was a cross-sectional association study. PATIENTS: A total of 1076 obese children/adolescents (age = 11.4 ± 2.8 years) and 1265 normal-weight young volunteers (age = 21.1 ± 4.4 years) of European ancestry were recruited from pediatric obesity clinics and general population, respectively. INTERVENTION: Standard OGTT was the intervention in this study. MAIN OUTCOME MEASURES: Associations between GRSs and OGTT-derived traits including fasting glucose and insulin, insulinogenic index, insulin sensitivity index, disposition index (DI) and associations between GRSs and pre-diabetic conditions were measured. RESULTS: GRS-ß significantly associated with fasting glucose (ß = 0.019; P = 3.5 × 10-4) and DI (ß = -0.031; P = 8.9 × 10-4, last quartile 18% lower than first) in obese children, and nominally associated with fasting glucose (ß = 0.009; P = 0.017) and DI (ß = -0.030; P = 1.1 × 10-3, last quartile 11% lower than first) in normal-weight youths. GRS-T2D showed weaker contribution to fasting glucose and DI compared to GRS-ß, in both obese and normal-weight youths. GRS associated with insulin resistance and GRS associated with body mass index did not associate with any traits. None of the GRSs associated with prediabetes, which affected only 4% of participants overall. CONCLUSION: Single nucleotide polymorphisms identified by genome-wide association studies to influence beta-cell function were associated with fasting glucose and indices of insulin secretion in youths, especially in obese children.

Annotating the Function of the Human Genome with Gene Ontology and Disease Ontology.

Increasing evidences indicated that function annotation of human genome in molecular level and phenotype level is very important for systematic analysis of genes. In this study, we presented a framework named Gene2Function to annotate Gene Reference into Functions (GeneRIFs), in which each functional description of GeneRIFs could be annotated by a text mining tool Open Biomedical Annotator (OBA), and each Entrez gene could be mapped to Human Genome Organisation Gene Nomenclature Committee (HGNC) gene symbol. After annotating all the records about human genes of GeneRIFs, 288,869 associations between 13,148 mRNAs and 7,182 terms, 9,496 associations between 948 microRNAs and 533 terms, and 901 associations between 139 long noncoding RNAs (lncRNAs) and 297 terms were obtained as a comprehensive annotation resource of human genome. High consistency of term frequency of individual gene (Pearson correlation = 0.6401, p = 2.2e - 16) and gene frequency of individual term (Pearson correlation = 0.1298, p = 3.686e - 14) in GeneRIFs and GOA shows our annotation resource is very reliable.