“Genetic risk score”

The relationship between genetic and environmental risk is complex and for many traits, estimates of genetic effects may be inflated by passive gene-environment correlation. This arises because biological offspring inherit both their genotypes and rearing environment from their parents. We tested for passive gene-environment correlation in adult body composition traits using the 'natural experiment' of childhood adoption, which removes passive gene-environment correlation within families. Specifically, we compared 6165 adoptees with propensity score matched non-adoptees in the UK Biobank...

OBJECTIVE: We sought to describe patient characteristics associated with prolonged post-operative length of stay in a contemporary cohort of infants who underwent isolated repair of aortic coarctation. METHODS: We reviewed patients less than 1 year of age who underwent isolated repair of aortic coarctation at our institution from 2009 to 2016. Prolonged post-operative length of stay was defined as length of stay within the upper tertile for the cohort. Bivariate and multi-variable analyses were performed to determine independent risk factors for prolonged length of stay...

Data on neurodevelopmental outcomes of infants born with esophageal atresia (EA) are still scarce and controversial. The aims of our study were to evaluate motor and cognitive development during the first year of life, in patients operated on of EA and to investigate potential risk factors for motor and cognitive development both at 6 and 12 months. This is an observational prospective longitudinal study in a selected cohort of type C and D EA infants enrolled in our follow-up program from 2009 to 2017. In order to exclude possible confounding factors, the following exclusion criteria were applied: (i) gestational age ≤ 32 weeks and/or birth weight ≤ 1500 g; (ii) genetic syndrome or chromosomal anomaly known to be associated with neurodevelopmental delay; (iii) neurologic disease; (iv) esophageal gap ≥three vertebral bodies...

SARS-CoV-2 is causative of pandemic COVID-19. There is a sequence similarity between SARS-CoV-2 and SARS-CoV; however, SARS-CoV-2 RBDs (receptor-binding domain) binds 20-fold strongly with human angiotensin-converting enzyme 2 (hACE2) than SARS-CoV. The study aims to investigate protein-protein interactions (PPI) of hACE2 with SARS-CoV-2 RBD between wild and variants to detect the most influential interaction. Variants of hACE2 were retrieved from NCBI and subjected to determine the most pathogenic nsSNPs. Probability of PPIs determines the binding affinity of hACE2 genetic variants with RBD was investigated...

Familial hypercholesterolemia (FH) is an underdiagnosed genetic inherited condition that may lead to premature coronary artery disease (CAD). FH has an estimated prevalence in the general population of about 1:313. However, its prevalence in patients with premature STEMI (ST-elevation myocardial infarction) has not been widely studied. This study aimed to evaluate the prevalence of FH in patients with premature STEMI. Cardiovascular risk factors, LDLc (low-density lipoprotein cholesterol) evolution, and differences between genders were also evaluated...

PURPOSE: To develop a prognostic tool to predict the live birth rate in cases of repeated pregnancy losses. STUDY DESIGN: A retrospective cohort study including patients treated in the dedicated RPL clinic between 2000 and 2015. Background data was collected in the primary visit via questionnaires and medical records. The repeated pregnancy loss workup includes a genetic testing, endocrine testing, and anatomic abnormalities as well as thrombophilia.The prognostic tool took into account the unique contribution of the different risk factors, including maternal age, number of pregnancy losses, primary vs...

Aging is a fundamental biological process that is still not fully understood. As many of the most significant human diseases have aging as their greatest risk factor, a better understanding of aging potentially has enormous practical implications in treating these diseases. The nematode C. elegans is an exceptionally useful genetic model organism that had been used with great success to shed light on many genes and pathways that are involved in aging. Many of these pathways and mechanisms have been shown to be conserved through mammals...

OBJECTIVE: To test the hypothesis that genetic risk for Alzheimer disease (AD) may represent a stable influence on the brain from early in life, rather than being primarily age dependent, we investigated in a lifespan sample of 1,181 persons with a total of 2,690 brain scans, whether higher polygenic risk score (PGS) for AD and presence of APOE ε4 was associated with lower hippocampal volumes to begin with, as an offset effect, or possibly faster decline in older age. METHODS: Using general additive mixed models, we assessed the relations of PGS for AD, including variants in APOE with hippocampal volume and its change in a cognitively healthy longitudinal lifespan sample (age range: 4-95 years, mean visit age 39...

Over the past 50 years, great progress has been made in the diagnosis and treatment of acute lymphoblastic leukemia (ALL), especially in pediatric patients. However, early recurrence is still an important threat to the survival of patients. In this study, we used integrated bioinformatics analysis to look for biomarkers of early recurrence of B-cell ALL (B-ALL) in childhood and adolescent patients. Firstly, we obtained gene expression profiles from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database and the Gene Expression Omnibus (GEO) database...

Although genome-wide association studies (GWASs) have successfully identified thousands of risk variants for human complex diseases, understanding the biological function and molecular mechanisms of the associated SNPs involved in complex diseases is challenging. Here we developed a framework named integrative multi-omics network-based approach (IMNA), aiming to identify potential key genes in regulatory networks by integrating molecular interactions across multiple biological scales, including GWAS signals, gene expression-based signatures, chromatin interactions and protein interactions from the network topology...

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with a strong genetic basis. The role of de novo mutations in ASD has been well established, but the set of genes implicated to date is still far from complete. The current study employs a machine learning-based approach to predict ASD risk genes using features from spatiotemporal gene expression patterns in human brain, gene-level constraint metrics, and other gene variation features. The genes identified through our prediction model were enriched for independent sets of ASD risk genes, and tended to be down-expressed in ASD brains, especially in frontal and parietal cortex...

A critical factor involved in the pathophysiology of Alzheimer's disease (AD) and related dementias is the decline of plasmalogens, a key glycerophospholipid required for normal neuron function. An accumulating body of evidence correlates low blood and brain plasmalogens with higher levels of AD pathology and lower cognition scores and indicates that declines in these phospholipids begin years before clinical symptoms develop. Furthermore, it has been recently reported that high blood plasmalogen levels neutralize the increased risk of dementia in persons who carry the APOE epsilon 4 allele, the most significant genetic risk factor for AD...

Non-alcoholic fatty liver disease (NAFLD) is among the most frequent etiologies of cirrhosis worldwide, and it is associated with features of metabolic syndrome; the key factor influencing its prognosis is the progression of liver fibrosis. This review aimed to propose a practical and stepwise approach to the evaluation and management of liver fibrosis in patients with NAFLD, analyzing the currently available literature. In the assessment of NAFLD patients, it is important to identify clinical, genetic, and environmental determinants of fibrosis development and its progression...

OBJECTIVE: To investigate the effect of a genetic report format using risk communication "best-practices" on risk perceptions, in part to reduce risk overestimates. METHODS: Adults (N = 470) from the Coriell Personalized Medicine Collaborative (CPMC) were randomized to a 2 × 2 experimental design to receive a hypothetical "personalized" genetic risk result for leukemia (relative risk = 1.5 or 2.5) through either the standard CPMC report (N = 232) or an enriched report informed by best practices (N = 238)...

BACKGROUND: Genetic variants can be used to prioritize risk factors as potential therapeutic targets via Mendelian randomization (MR). An agnostic statistical framework using Bayesian model averaging (MR-BMA) can disentangle the causal role of correlated risk factors with shared genetic predictors. Here, our objective is to identify lipoprotein measures as mediators between lipid-associated genetic variants and coronary artery disease (CAD) for the purpose of detecting therapeutic targets for CAD...

BACKGROUND: Preimplantation genetic testing is commonly performed by removing cells from the trophectoderm, the outer layer of the blastocyst, which subsequently forms the placenta. Because preimplantation genetic testing removes the cells that are destined to form the placenta, it is possible that preimplantation genetic testing could be associated with an increased risk for adverse outcomes associated with abnormal placentation. Despite the increasing utilization of preimplantation genetic testing, few studies have investigated the perinatal outcomes, with published studies yielding contradictory findings and using small sample sizes...

BACKGROUND: Aging is associated with an increasing risk of decline in cognitive abilities. The decline is, however, not a homogeneous process. There are substantial differences across individuals although previous investigations have identified individuals with distinct cognitive trajectories. Evidence is accumulating that lifestyle contributes significantly to the classification of individuals into various clusters. How and whether genetically related individuals, like twins, change in a more similar manner is yet not fully understood...

OBJECTIVES: Acinetobacter seifertii, a new member of the Acinetobacter baumannii group, has emerged as a cause of severe infections in humans. We investigated the clinical and molecular characteristics of A. seifertii. PATIENTS AND METHODS: This retrospective study enrolled 80 adults with A. seifertii bloodstream infection (BSI) at four medical centres over an 8 year period. Species identification was confirmed by MALDI-TOF MS, rpoB sequencing and WGS. Molecular typing was performed by MLST...

The association between obesity and attention-deficit hyperactivity disorder (ADHD) has been extensively reported in the literature. However, the potential mechanisms underlying this association are not completely understood. This study aimed to evaluate the association between body composition and ADHD and explore the possible genetic mechanisms involved. We used data from the 1982 Pelotas (Brazil) Birth Cohort at age 30-year follow-up (N = 3630). We first used logistic regression analysis to test whether body mass index (BMI), fat mass (FM), and fat-free mass (FFM) were associated with ADHD...

Among Latin American women, breast cancer incidences vary across populations. Uruguay and Argentina have the highest rates in South America, which are mainly attributed to strong, genetic European contributions. Most genetic variants associated with breast cancer were described in European populations. However, the vast majority of genetic contributors to breast cancer risk remain unknown. Here, we report the results of a candidate gene association study of sporadic breast cancer in 176 cases and 183 controls in the Uruguayan population...