Genotype-by-Environment Interactions in Nonalcoholic Fatty Liver Disease and Chronic Illness among Mexican Americans: The Role of Acculturation Stress.

This study examines the complex interplay of genetic and environmental interactions that shape chronic illness risk. Evidence is mounting for the role of genetic expression and the immune response in the pathogenesis of chronic disease. In the Rio Grande Valley of south Texas, where 90% of the population is Mexican American, chronic illnesses (including obesity, diabetes, nonalcoholic liver disease, and depression) are reaching epidemic proportions.

Exosomes derived from tumor adjacent fibroblasts efficiently target pancreatic tumors.

The application of extracellular vesicles, particularly exosomes (EXs), is rapidly expanding in the field of medicine, owing to their remarkable properties as natural carriers of biological cargo. This study investigates utilization of exosomes derived from stromal cells of tumor adjacent normal tissues (NAF-EXs) for personalized medicine, which can be derived at the time of diagnosis by endoscopic ultrasound. Herein, we show that exosomes (EXs) derived from NAFs demonstrate differential bio-physical characteristics, efficient cellular internalization, drug loading efficiency, pancreatic tumor targeting and delivery of payloads.

Statistical Genetic Approaches to Investigate Genotype-by-Environment Interaction: Review and Novel Extension of Models.

Statistical genetic models of genotype-by-environment (G×E) interaction can be divided into two general classes, one on G×E interaction in response to dichotomous environments (e.g., sex, disease-affection status, or presence/absence of an exposure) and the other in response to continuous environments (e.

Gene-by-Environment Interaction in Non-Alcoholic Fatty Liver Disease and Depression: The Role of Hepatic Transaminases.

Non-alcoholic fatty liver disease (NAFLD) encompasses a range of liver conditions, from benign fatty accumulation to severe fibrosis. The global prevalence of NAFLD has risen to 25-30%, with variations across ethnic groups. NAFLD may advance to hepatocellular carcinoma, increases cardiovascular risk, is associated with chronic kidney disease, and is an independent metabolic disease risk factor.

Metabolic syndrome traits exhibit genotype-by-environment interaction in relation to socioeconomic status in the Mexican American family heart study.

Socioeconomic Status (SES) is a potent environmental determinant of health. To our knowledge, no assessment of genotype-environment interaction has been conducted to consider the joint effects of socioeconomic status and genetics on risk for metabolic disease. We analyzed data from the Mexican American Family Studies (MAFS) to evaluate the hypothesis that genotype-by-environment interaction (GxE) is an essential determinant of variation in risk factors for metabolic syndrome (MS).

Frailty index in the Colonias of the Rio Grande Valley: health related quality of life and resilience.

Background: Frailty is characterized by an accumulation of deficits that lead to vulnerability to adverse health outcomes. The Frailty Index (FI) quantifies frailty by measuring deficits that increase susceptibility to stressors. This study focused on a population of Mexican Americans living in vulnerable communities in the Rio Grande Valley of south Texas.

Non-alcoholic Fatty Liver Disease and Depression: Evidence for Genotype × Environment Interaction in Mexican Americans.

This study examines the impact of G × E interaction effects on non-alcoholic fatty liver disease (NAFLD) among Mexican Americans in the Rio Grande Valley (RGV) of South Texas. We examined potential G × E interaction using variance components models and likelihood-based statistical inference in the phenotypic expression of NAFLD, including hepatic steatosis and hepatic fibrosis (identified using vibration controlled transient elastography and controlled attenuation parameter measured by the FibroScan Device). We screened for depression using the Beck Depression Inventory-II (BDI-II).

Influence of the Human Lipidome on Epicardial Fat Volume in Mexican American Individuals.

Introduction: Cardiovascular disease (CVD) is the leading cause of mortality worldwide and is the leading cause of death in the US. Lipid dysregulation is a well-known precursor to metabolic diseases, including CVD. There is a growing body of literature that suggests MRI-derived epicardial fat volume, or epicardial adipose tissue (EAT) volume, is linked to the development of coronary artery disease.

Frailty Index in the Colonias on the US-Mexico Border: A Special Report.

Frailty is the age-related decline in well-being. The Frailty index (FI) measures the accumulation of health deficits and reflects biopsychosocial and cultural determinants of well-being. Frailty is measured as a static phenotype or as a Frailty Index comprising a ratio of suffered health deficits and total deficits.

Estimating the Heritability of Experiencing Child Maltreatment in an Extended Family Design.

Child-driven genetic factors can contribute to negative parenting and may increase the risk of being maltreated. Experiencing childhood maltreatment may be partly heritable, but results of twin studies are mixed. In the current study, we used a cross-sectional extended family design to estimate genetic and environmental effects on experiencing child maltreatment.

Quantitative HLA-class-II/factor VIII (FVIII) peptidomic variation in dendritic cells correlates with the immunogenic potential of therapeutic FVIII proteins in hemophilia A.

Background: Plasma-derived (pd) or recombinant (r) therapeutic factor VIII proteins (FVIIIs) are infused to arrest/prevent bleeding in patients with hemophilia A (PWHA). However, FVIIIs are neutralized if anti-FVIII-antibodies (inhibitors) develop. Accumulating evidence suggests that pdFVIIIs with von Willebrand factor (VWF) are less immunogenic than rFVIIIs and that distinct rFVIIIs are differentially immunogenic.

UniMóvil: A Mobile Health Clinic Providing Primary Care to the Colonias of the Rio Grande Valley, South Texas.

We describe a mobile unit () designed to improve poor healthcare access delivery to residents in two South Texas underserved Colonias. The interprofessional team measured seven clinical outcomes [obesity, diabetes, hypertension, hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-C) levels, and depression], and using the Duke Health Profile, assessed the health-related quality of life (HrQoL). The investigators used previously reported disease prevalence, an implementation model, and community needs-assessments to design an outreach healthcare delivery model.

Peptides identified on monocyte-derived dendritic cells: a marker for clinical immunogenicity to FVIII products.

The immunogenicity of protein therapeutics is an important safety and efficacy concern during drug development and regulation. Strategies to identify individuals and subpopulations at risk for an undesirable immune response represent an important unmet need. The major histocompatibility complex (MHC)-associated peptide proteomics (MAPPs) assay directly identifies the presence of peptides derived from a specific protein therapeutic on a donor's MHC class II (MHC-II) proteins.

The genetic and environmental etiology of child maltreatment in a parent-based extended family design.

Child maltreatment has been associated with various cumulative risk factors. However, little is known about the extent to which genetic and environmental factors contribute to individual differences between parents in perpetrating child maltreatment. To estimate the relative contribution of genetic and environmental factors to perpetrating maltreatment we used a parent-based extended family design.

Genetic and environmental (physical fitness and sedentary activity) interaction effects on cardiometabolic risk factors in Mexican American children and adolescents.

Knowledge on genetic and environmental (G × E) interaction effects on cardiometabolic risk factors (CMRFs) in children is limited.  The purpose of this study was to examine the impact of G × E interaction effects on CMRFs in Mexican American (MA) children (n = 617, ages 6-17 years). The environments examined were sedentary activity (SA), assessed by recalls from "yesterday" (SAy) and "usually" (SAu) and physical fitness (PF) assessed by Harvard PF scores (HPFS).

Sex-specific genetic effects in physical activity: results from a quantitative genetic analysis.

Background: The objective of this study is to present a model to estimate sex-specific genetic effects on physical activity (PA) levels and sedentary behaviour (SB) using three generation families.

Methods: The sample consisted of 100 families covering three generations from Portugal. PA and SB were assessed via the International Physical Activity Questionnaire short form (IPAQ-SF).

Evaluation of estimated genetic values and their application to genome-wide investigation of systolic blood pressure.

The concept of breeding values, an individual's phenotypic deviation from the population mean as a result of the sum of the average effects of the genes they carry, is of great importance in livestock, aquaculture, and cash crop industries where emphasis is placed on an individual's potential to pass desirable phenotypes on to the next generation. As breeding or genetic values (as referred to here) cannot be measured directly, estimated genetic values (EGVs) are based on an individual's own phenotype, phenotype information from relatives, and, increasingly, genetic data. Because EGVs represent additive genetic variation, calculating EGVs in an extended human pedigree is expected to provide a more refined phenotype for genetic analyses.

Genotype by sex and genotype by age interactions with sedentary behavior: the Portuguese Healthy Family Study.

Sedentary behavior (SB) expression and its underlying causal factors have been progressively studied, as it is a major determinant of decreased health quality. In the present study we applied Genotype x Age (GxAge) and Genotype x Sex (GxSex) interaction methods to determine if the phenotypic expression of different SB traits is influenced by an interaction between genetic architecture and both age and sex. A total of 1345 subjects, comprising 249 fathers, 327 mothers, 334 sons and 325 daughters, from 339 families of The Portuguese Healthy Family Study were included in the analysis.

Genetic prediction in the Genetic Analysis Workshop 18 sequencing data.

High-throughput sequencing data can be used to predict phenotypes from genotypes, and this corresponds to establishing a prognostic model. In extended pedigrees the relatedness of subjects provides additional information so that genetic values, fixed or random genetic components, and heritability can be estimated. At the Genetic Analysis Workshop 18, the working group on genetic prediction dealt with both establishing a prognostic model and, in one contribution, comparing standard logistic regression with robust logistic regression in a sample of unrelated affected or unaffected individuals.

Plasma levels of soluble interleukin 1 receptor accessory protein are reduced in obesity.

Context: Adipokines actuate chronic, low-grade inflammation through a complex network of immune markers, but the current understanding of these networks is incomplete. The soluble isoform of the IL-1 receptor accessory protein (sIL1RAP) occupies an important position in the inflammatory pathways involved in obesity. The pathogenetic and clinical influences of sIL1RAP are unknown.

Genotype by energy expenditure interaction with metabolic syndrome traits: the Portuguese healthy family study.

Moderate-to-high levels of physical activity are established as preventive factors in metabolic syndrome development. However, there is variability in the phenotypic expression of metabolic syndrome under distinct physical activity conditions. In the present study we applied a Genotype X Environment interaction method to examine the presence of GxEE interaction in the phenotypic expression of metabolic syndrome.

Genetic basis of neurocognitive decline and reduced white-matter integrity in normal human brain aging.

Identification of genes associated with brain aging should markedly improve our understanding of the biological processes that govern normal age-related decline. However, challenges to identifying genes that facilitate successful brain aging are considerable, including a lack of established phenotypes and difficulties in modeling the effects of aging per se, rather than genes that influence the underlying trait. In a large cohort of randomly selected pedigrees (n = 1,129 subjects), we documented profound aging effects from young adulthood to old age (18-83 y) on neurocognitive ability and diffusion-based white-matter measures.

Clustering of body composition, blood pressure and physical activity in Portuguese families.

Aim: The purposes of this study were: (i) to identify familial resemblances in body fat, blood pressure (BP) and total physical activity (TPA); (ii) to estimate the magnitude of their genetic and environmental influences; and (iii) to investigate shared familial aggregation among these phenotypes.

Subjects And Methods: The sample comprised 260 nuclear families from Portugal. Body fat was assessed by bioelectrical impedance.

Gene-by-age effects on BMI from birth to adulthood: the Fels Longitudinal Study.

Objectives: Genome wide association studies have shown 32 loci to influence BMI in European-American adults but replication in other studies is inconsistent and may be attributed to gene-by-age effects. The aims of this study were to determine if the influence of the summed risk score of these 32 loci (GRS) on BMI differed across age from birth to 40 years, and to determine if additive genetic effects other than those in the GRS differed by age.

Methods: Serial measures of BMI were calculated at 0, 1, 3, 6, 9, 12, 18, and 28 months, and 4, 7, 11, 15, 19, 23, 30, and 40 years for 1,176 (605 females, 571 males) European-American participants in the Fels Longitudinal Study.