Gene-environment Interactions Research Articles

Ex vivo and in vitro methods as a platform for studying anthropogenic effects on marine mammals: four challenges and how to meet them

Marine mammals are integral to global biodiversity and marine health through their roles in coastal, benthic, and pelagic ecosystems. Marine mammals face escalating threats from climate change, pollution, and human activities, which perturb their oceanic environment. The diverse biology and extreme adaptations evolved by marine mammals make them important study subjects for understanding anthropogenic pressures on marine ecosystems. However, ethical and logistical constraints restrict the tractability of experimental research with live marine mammals. Additionally, studies on the effects of changing ocean environments are further complicated by intricate gene-environment interactions across populations and species. These obstacles can be overcome with a comprehensive strategy that involves a systems-level approach integrating genotype to phenotype using rigorously defined experimental conditions in vitro and ex vivo. A thorough analysis of the interactions between the genetics of marine mammals and their exposure to anthropogenic pressures will enable robust predictions about how global environmental changes will affect their health and populations. In this perspective, we discuss four challenges of implementing such non-invasive approaches across scientific fields and international borders: 1) practical and ethical limitations of in vivo experimentation with marine mammals, 2) accessibility to relevant tissue samples and cell cultures; 3) open access to harmonized methods and datasets and 4) ethical and equitable research practices. Successful implementation of the proposed approach has the potential impact to inspire new solutions and strategies for marine conservation.

Identification of foxtail millet (Seteria italica (L.) P. Beauv.) genotypes for multi-season adaptability using GGE biplot analysis in Foothills of Nagaland

Foxtail millet is a main millets crop of Northeastern region of India. The genotype-by-environment analyses assist in understanding the potential performance of the genotypes over environments. The present study aimed to investigate the 30 foxtail genotypes over the four different environments to identify the genotypes with stable yield in this region. The investigation was carried out during July 2022 to May 2023 for four different dates of sowing with fifty-five days interval. Two environments maintained under rainfed condition and the remaining two environments are maintained under irrigated condition with seven days interval. The experiment was conducted in randomized complete block design with three replications in all environments. Genotype-environment interactions significantly influenced grain yield across four environments, while replicates were non-significant. Pooled analysis revealed significant genotypic effects and seasonal impacts. The “discriminating power vs. representativeness” GGE biplot showed that E4 (showing dates in January 2ndfort night) is the most ideal test environment for foxtail millet elite line selection based on discriminative ability and representativeness. The accessions that performed best in each environment based on “which-won-where” polygon biplot, genotypes G19 (FOX 4392) and G27 (FOX 4420) showed superior and stable performance in E1, however G25 (FOX 4341) and G1 (ELS 20) excelled in E2, E3, and E4.Mean vs stability biplots exposed G1 (ELS 20) is stable and high yielding performance. Ranking genotypes GGE biplot identify the G25 (FOX 4341) is an ideal genotype due to its higher yield and stability compared to the other genotypes. Keywords: GGE Biplots, Foxtail millet, Tukey's Honest Significant Difference (HSD) Test

Genotype-Environment Interaction and Phenotypic Stability Analysis for Grain Yield of Durum Wheat in the Misurata Region

تهدف هذه الدراسة إلى تقييم التداخل بين التركيب الوراثي (GE)، والبيئة، وتحديد سلالات القمح الصلب (Triticum turgidum var. durum) المناسبة لإنتاج الحبوب في منطقة مصراتة - ليبيا. تم تقييم خمس عشرة سلالة، وصنف من القمح الصلب تحت الري التكميلي باستخدام تصميم القطاعات الكاملة العشوائية بثلاث مكررات. نفذت الدراسة لمدة 5 سنوات. وتم تحليل التداخل GE باستخدام تقنيات الانحدار الخطي. أوضحت النتائج وجود فروق معنوية عالية في صفة إنتاج الحبوب بين التراكيب الوراثية. أجري تقدير الثباتية وفقًا لتحليل الثبات باستخدام طريقة Eberhart، و Russell، كان التركيب الوراثي G9 هو الأكثر استقرارًا في صفة إنتاج محصول الحبوب. معامل الانحدار للسلالة G9 كان وحدة تقريبًا (bi = 1) وسجل أدنى انحراف عن معامل الانحدار (S2di) . في المقابل، أظهرت السلالات G10، و G3 معامل انحدار أكبر من 1.0، مما يشير إلى تأثرهما الكبير بالتغيرات البيئية لصفة محصول الحبوب. سجل أعلى محصول للسلالات G10، وG9بـ 3.65، و 3.19 طن/هكتار على التوالي متوسطا لكل البيئات. أظهرت السلالة G10 أعلى محصول للحبوب، ومعامل انحدار أكبر من الواحد، مما يشير إلى أنها حساسة للتغير البيئي، ويمكن التوصية بها تحت ظروف الزراعة المروية.

Foxe1 mutant zebrafish show indications of a hypothyroid phenotype and increased sensitivity to ethanol for craniofacial malformations.

FOXE1 mutations in humans are associated with cleft palate and hypothyroidism. We previously developed a foxe1 mutant zebrafish demonstrating mineralization defects in larvae. In the present study, we investigate the thyroid status and skeletal phenotype of adult foxe1 mutants. Mutant fish have increased expression of tshβ in the pituitary, and of hepatic dio1 and dio2. In plasma, we found higher Mg levels. Together these findings are indicative of hypothyroidism. We further observed mineralization defects in scales due to enhanced osteoclast activity as measured by increased expression levels of tracp, ctsk, and rankl. Gene-environment interactions in the etiology of FOXE1-related craniofacial abnormalities remain elusive, which prompts the need for models to investigate genotype-phenotype associations. We here investigated whether ethanol exposure increases the risk of developing craniofacial malformations in foxe1 mutant larvae that we compared to wild types. We found in ethanol-exposed mutants an increased incidence of developmental malformations and marked changes in gene expression patterns of cartilage markers (sox9a), apoptotic markers (casp3b), retinoic acid metabolism (cyp26c1), and tissue hypoxia markers (hifaa, hifab). Taken together, this study shows that the foxe1 mutant zebrafish recapitulates phenotypes associated with FOXE1 mutations in human patients and a clear foxe1-ethanol interaction.

Genetic and environmental influences on fatty acid composition in different fenugreek genotypes

Fenugreek (Trigonella foenum-graecum L.) plays a crucial role in both the food and pharmaceutical industries due to its rich nutritional profile and medicinal properties, such as regulating blood sugar and reducing inflammation. This study offers a comprehensive analysis of the fatty acid composition in fenugreek seeds, revealing significant variability influenced by genetic and environmental factors. The analysis showed that linoleic acid ranged from 32.16 % to 45.96 %, linolenic acid from 17.3 % to 31.21 %, oleic acid from 11.40 % to 20.32 %, stearic acid from 3.78 % to 6.76 %, and palmitic acid from 8.74 % to 16.44 %. Both genotype and environmental conditions had a profound impact on these profiles, with notable variations arising from differences in water availability. The Israel and Kermanshah (Iran) genotypes recorded the highest linoleic acid levels under irrigated conditions, while the Kayseri (Turkey) genotype exhibited the highest linolenic and stearic acid values across both irrigated and non-irrigated environments. Additionally, the Ahvaz (Iran) and Ukraine genotypes excelled in oleic and palmitic acid concentrations. Principal component analysis (PCA) and Additive Main Effects and Multiplicative Interaction (AMMI) biplots further highlighted the complex genotype-environment interactions, providing essential insights for breeding fenugreek varieties optimized for diverse agro-climatic conditions.

Age-at-migration, ethnicity and psychosis risk: Findings from the EU-GEI case-control study

Several studies have highlighted increased psychosis risk in migrant and minority ethnic populations. Migration before age 18 appears to increase risk, but further evidence is required. We investigated this issue in a European case-control study. We hypothesized that migration during two key socio-developmental periods, childhood and adolescence, would be most strongly associated with increased odds of psychosis, and that this would be more pronounced for racialised minorities. We used data from five countries in the EUropean network of national schizophrenia networks studying Gene-Environment Interactions [EU-GEI] study. We examined the association between migration in infancy (0–4 years), childhood (5–10 years), adolescence (11–17 years) or adulthood (18+ years) and first episode psychotic disorder. We fitted unadjusted and adjusted logistic regression models to estimate odds ratios [OR] and 95% confidence intervals [95%CI] for associations between age-at-migration and psychosis. In stratified models, we also examined whether these associations varied by ethnicity. The sample consisted of 937 cases and 1,195 controls. Migration at all ages, including infancy (OR: 2.03, 95%CI: 1.01–4.10), childhood (OR: 2.07, 95%CI: 1.04–4.14), adolescence (OR: 3.26, 95%CI: 1.89–5.63) and adulthood (OR: 1.71, 95%CI: 1.21–2.41), was associated with increased odds of psychosis compared with the white majority non-migrant group, after adjustment for all confounders except ethnoracial identity. After additional adjustment for ethnoracial identity, only migration during adolescence remained associated with psychosis (OR 1.94, 95%CI: 1.11–3.36). In stratified analyses, migration during adolescence was associated with increased odds of psychosis in Black (OR: 6.52, 95%CI: 3.00–14.20) and North African (OR: 16.43, 95%CI: 1.88–143.51) groups.Migration during adolescence increased psychosis risk, particularly in racially minoritised young people. This suggests that development of interventions for minoritised young migrants that alleviate stressors associated with migration and acculturation are warranted.

Genome-Wide DNA Methylation Profiling Reveals Low Methylation Variability in Moyamoya Disease.

Moyamoya disease (MMD) is a chronic cerebrovascular disorder that can lead to stroke and neurological dysfunctions. Given the largely sporadic nature and the role of gene-environment interactions in various diseases, we examined epigenetic modifications in MMD. We performed genome-wide DNA methylation using Illumina 850K Methylation EPIC BeadChip, in two racially distinct adult female cohorts: a non-Asian cohort (13 MMD patients and 7 healthy controls) and an Asian cohort (14 MMD patients and 3 healthy controls). An additional external cohort with both sexes (females: 5 MMD patients and 5 healthy controls, males: 5 MMD patients and 5 healthy controls) was included for validation. Our findings revealed strikingly low DNA methylation variability between MMD patients and healthy controls, in both MMD female cohorts. In the non-Asian cohort, only 6 probes showed increased variability versus 647 probes that showed decreased variability. Similarly, in the Asian cohort, the MMD group also displayed a reduced methylation variability across all 2845 probes. Subsequent analysis showed that these differentially variable probes are located on genes involved in key biological processes such as methylation and transcription, DNA repair, cytoskeletal remodeling, natural killer cell signaling, cellular growth, and migration. These findings mark the first observation of low methylation variability in any disease, contrasting with the high variability observed in other disorders. This reduced methylation variability in MMD may hinder patients' adaptability to environmental shifts, such as hemodynamic stress, thereby influencing vascular homeostasis and contributing to MMD pathology. These findings offer new insights into the mechanisms of MMD and potential treatment strategies.

What explains the sex differences in family leisure activities of children? A genetically sensitive analysis with twin data

Objective: This paper examines to what extent genetic and environmental influences contribute to differences in family leisure activities of girls and boys. Background: While family leisure activities have been described as relevant for child development, it remains unclear what accounts for differences in the leisure behavior of girls and boys. While research emphasized the importance of the environment, e.g., in relation to gender role socialization, other studies pointed to biological and, thus, genetic differences as explanatory factors. Method: The analysis is based on 954 female and 1036 male twins aged 10-12 years who are part of the first wave of the German Twin Family Panel Study. Our analysis examines five family leisure activities using variance decompositions and gene-environment interaction models. Results: Overall, there were only minor differences between girls and boys in the contributions of genes and environments to family leisure activities. Only for singing and making music did influences from the environment common to both twins contribute more strongly to the performance of these activities in the girls than in the boys. Conclusion: There is no evidence that genetic differences lead to differences in family leisure behavior between girls and boys in the activities considered here. Existing differences are more likely to be due to environmental influences.

A comprehensive multivariate approach for GxE interaction analysis in early maturing rice varieties

The genotype evaluation process requires analysis of GxE interactions to ascertain the responsiveness of a genotype to various environments, including the development of early maturing rice. However, the concept of interaction is relatively specific to grain yield. In contrast, grain yield is highly polygenic, so assessment should be carried out with multivariate approaches. Therefore, multivariate assessment in evaluating GxE interactions should be developed, especially for early maturing rice genotypes. The study aimed to develop a comprehensive multivariate approach to improve the comprehensiveness and responsiveness of GxE interaction analysis. The study was conducted in Bone and Soppeng districts, South Sulawesi, Indonesia, in two seasons. The study used a randomized complete block design, where replications were nested across two seasons and locations. Two check varieties and five early maturing varieties were replicated three times in each environment. Based on this study, a new approach to GxE interaction analysis based on multiple regression index analysis, BLUP analysis, factor analysis, and path analysis was considered adequate, especially for evaluating early maturing rice. This approach combined days to harvest, biological yield, and grain yield in multiple linear regression with weighting based on the combination of all analyses. The effectiveness of the GxE interaction assessment was reflected by high coefficient of determination (R2) and gradient (b) values above 0.8 and 0.9, respectively. Inpari 13 (R2 = 0.9; b=1.05), Cakrabuana (R2 = 0.98; b=0.99), and Padjajaran (R2 = 0.95; b=1.07) also have good grain yield with days to harvesting consideration, namely 7.83 ton ha-1, 98.12 days; 7.37 ton ha-1, 95.52 days; and 7.29 ton ha-1, 97.23 days, respectively. Therefore, this index approach can be recommended in GxE interaction analysis to evaluate early maturing rice genotypes. Furthermore, Inpari 13, Cakrabuana, and Padjajaran are recommended as adaptive early maturing varieties.

Exposure to Air Pollutants and Myocardial Infarction Incidence: A UK Biobank Study Exploring Gene-Environment Interaction.

Unraveling gene-environment interaction can provide a novel insight into early disease prevention. Nevertheless, current understanding of the interplay between genetic predisposition and air pollution in relation to myocardial infarction (MI) risk remains limited. Furthermore, the potential long-term influence of air pollutants on MI incidence risk warrants more conclusive evidence in a community population. We investigated interactions between genetic predisposition and exposure to air pollutants on MI incidence. This study incorporated a sample of 456,354 UK Biobank participants and annual mean air pollution (, , , and ) from the UK Department for Environment, Food and Rural Affairs (2006-2021). The Cox proportional hazards model was employed to explore MI incidence after chronic air pollutants exposure. By quantifying genetic risk through the calculation of polygenic risk score (PRS), this study further examined the interactions between genetic risk and exposure to air pollutants in the development of MI on both additive and multiplicative scales. Among 456,354 participants, 9,114 incident MI events were observed during a median follow-up of 12.08 y. Chronic exposure to air pollutants was linked with an increased risk of MI occurrence. Specifically, the hazard ratios (per interquartile range) were 1.12 (95% CI: 1.10, 1.13) for , 1.20 (95% CI: 1.19, 1.22) for , 1.13 (95% CI: 1.12, 1.15) for , and 1.12 (95% CI: 1.11, 1.13) for . In terms of the joint effects, participants with high PRS and high level of air pollution exposure exhibited the greatest risk of MI among all study participants ( to 324%). Remarkably, both multiplicative and additive interactions were detected in the ambient air pollutants exposure and genetic risk on the incidence of MI. There were interactions between exposure to ambient air pollutants and genetic susceptibility on the risk of MI onset. Moreover, the joint effects of these two exposures were greater than the effect of each factor alone. https://doi.org/10.1289/EHP14291.

Understanding species limits through the formation of phylogeographic lineages.

The outcomes of speciation across organismal dimensions (e.g., ecological, genetic, phenotypic) are often assessed using phylogeographic methods. At one extreme, reproductively isolated lineages represent easily delimitable species differing in many or all dimensions, and at the other, geographically distinct genetic segments introgress across broad environmental gradients with limited phenotypic disparity. In the ambiguous gray zone of speciation, where lineages are genetically delimitable but still interacting ecologically, it is expected that these lineages represent species in the context of ontology and the evolutionary species concept when they are maintained over time with geographically well-defined hybrid zones, particularly at the intersection of distinct environments. As a result, genetic structure is correlated with environmental differences and not space alone, and a subset of genes fail to introgress across these zones as underlying genomic differences accumulate. We present a set of tests that synthesize species delimitation with the speciation process. We can thereby assess historical demographics and diversification processes while understanding how lineages are maintained through space and time by exploring spatial and genome clines, genotype-environment interactions, and genome scans for selected loci. Employing these tests in eight lineage-pairs of snakes in North America, we show that six pairs represent 12 "good" species and that two pairs represent local adaptation and regional population structure. The distinct species pairs all have the signature of divergence before or near the mid-Pleistocene, often with low migration, stable hybrid zones of varying size, and a subset of loci showing selection on alleles at the hybrid zone corresponding to transitions between distinct ecoregions. Locally adapted populations are younger, exhibit higher migration, and less ecological differentiation. Our results demonstrate that interacting lineages can be delimited using phylogeographic and population genetic methods that properly integrate spatial, temporal, and environmental data.

An adaptive dynamical system model for development of schizophrenia: Epigenetics and false memories

This paper introduces a fifth-order adaptive dynamical system model represented as a self-modelling network model to understand the role of epigenetic factors in developing schizophrenia, particularly about the occurrence of false memories. Schizophrenia, affecting a significant portion of the global population, presents complex challenges due to its symptoms across cognitive, emotional, and social domains. Central to this paper is the exploration of epigenetic influences on the development of schizophrenia, with a focus on how these epigenetic factors contribute to the generation of false memories, a notable symptom of the disorder. The model assumes that early adverse experiences significantly affect hippocampal development, which is crucial for memory processes. By employing a fifth-order adaptive dynamical system model represented as a self-modelling network, this paper examines the intricate dynamics between genetic predispositions, environmental factors, and epigenetic modifications in schizophrenia. The model’s sophistication allows for a nuanced understanding of the gene-environment interactions, particularly highlighting the role of early-life trauma in shaping lifelong cognitive outcomes. This approach offers a comprehensive framework for analyzing the multifaceted nature of schizophrenia, contributing to a deeper understanding of its etiology and progression.

A genome-wide gene-environmental interaction study identified novel loci for the relationship between ambient air pollution exposure and depression, anxiety

BackgroundGenetic factors and environmental exposures, including air pollution, contribute to the risk of depression and anxiety. While the association between air pollution and depression and anxiety has been established in the UK Biobank, there has been limited research exploring this relationship from a genetic perspective. MethodsBased on individual genotypic and phenotypic data from a cohort of 104,385 participants in the UK Biobank, a polygenic risk score for depression and anxiety was constructed to explore the joint effects of nitric oxide (NO), nitrogen dioxide (NO2), particulate matter (PM) with a diameter of ⩽2.5 μm (PM2.5) and 2.5–10 μm (PMcoarse) with depression and anxiety by linear and logistic regression models. Subsequently, a genome-wide gene-environmental interaction study (GWEIS) was performed using PLINK 2.0 to identify the genes interacting with air pollution for depression and anxiety. ResultsA substantial risk of depression and anxiety development was detected in participants exposed to the high air pollution concomitantly with high genetic risk. GWEIS identified 166, 23, 18, and 164 significant candidate loci interacting with NO, NO2, PM2.5, and PMcoarse for Patient Health Questionnaire-9 (PHQ-9) score, and detected 44, 10, 10, and 114 candidate loci associated with NO, NO2, PM2.5, and PMcoarse for General Anxiety Disorder (GAD-7) score, respectively. And some significant genes overlapped among four air pollutants, like TSN (rs184699498, PNO2 = 3.47 × 10−9; rs139212326, PPM2.5 = 1.51 × 10−8) and HSP90AB7P(rs150987455, PNO2 = 1.63 × 10−11; rs150987455, PPM2.5 = 7.64 × 10−11), which were common genes affecting PHQ-9 score for both NO2 and PM2.5. ConclusionOur study identified the joint effects of air pollution with genetic susceptibility on the risk of depression and anxiety, and provided several novel candidate genes for the interaction, contributing to an understanding of the genetic architecture of depression and anxiety.

Связь полиморфизма rs11546155 гена GGT7 с риском развития ишемического инсульта

Background: Since oxidative stress plays a role in the pathogenesis of ischemic stroke (IS), it is important to investigate the molecular mechanisms contributing to redox homeostasis and glutathione metabolism. The aim of the study: To analyze the association of the rs11546155 polymorphism of gamma-glutamyltransferase 7 (GGT7) gene with the risk of ischemic stroke. Materials and methods: DNA samples from 600 patients with IS and 688 controls were used for genotyping SNP rs11546155 by real-time PCR with allele discrimination using TaqMan probes. Results: It was found that genotypes G/A and A/A are associated with an increased risk of IS in females (OR=1.54, 95%CI 1.02–2.32, Pperm=0.04), while no associations between rs11546155 genotypes were observed in males. In patients with hypodynamia, the rs11546155 polymorphism was associated with an increased risk of IS (OR=1.59, 95%CI 1.01–2.00, Pperm=0.04), while in individuals with normal and increased physical activity, the SNP did not influence disease risk. Moreover, the carriers of allele rs11546155G who did not abuse alcohol possess a decreased risk of IS (OR = 1.59, 95%CI 1.012.00, Pperm = 0.04), while the protective effect of the allele against disease risk was not seen in alcohol abusers. Functional SNP annotation showed that the IS-related rs11546155A allele is associated with decreased expression of the GGT7 gene, as well as genes involved in autophagy and proteasomal protein degradation. Conclusion: This study was the first to establish the association of the rs11546155 polymorphism with the risk of IS. Further studies are needed to clarify the nature of the sex-specific SNP association and gene-environment interactions.

New developments in the diagnosis and management of motor neuron disease.

Motor neuron disease (MND) is a devastating neurodegenerative disease characterized by progressive muscle weakness. PubMed, MEDLINE, and Cochrane databases were searched for articles to March 2024. Searches involved the terms 'motor neuron disease' or 'amyotrophic lateral sclerosis' and 'epidemiology', 'diagnosis', 'clinical', 'genetic', 'management', 'treatment', or 'trial'. Evidence-based management involves riluzole, multidisciplinary care, provision of noninvasive ventilation and gastrostomy, and symptomatic treatments. Tofersen should be offered to treat SOD1-MND. Edaravone and Relyvrio are approved treatments in the USA, but insufficient evidence was found to support approval in the UK and Europe. The discovery of neurofilaments as MND biomarkers, growth of platform trials and development of novel therapies provide optimism for more powerful neuroprotective therapies. Further work should focus on the elucidation of environmental causes of MND, gene-environment interactions, and advanced cellular models of disease.

Influence of different environmental challenges on the expression of reproductive traits in Holstein cattle in Southern Brazil.

The aim of this study was to assess the impact of genotype-environment interaction (GEI) on the manifestation of traits such as age at first calving (AFC), age at first service (AFS), and calving interval (CI) through the application of the reaction norm model in Holstein cattle raised in Paraná state, Brazil. Utilizing data from the milk testing service of the Paraná Association of Holstein Cattle Breeders (APCBRH), this study analyzed records from 179,492 animals undergoing their first, second, and third lactations from the years 2012 to 2022. These animals were part of 513 herds spread across 72 municipalities in Paraná. The environmental gradient was established by normalizing contemporary group solutions, derived from the animal model, with the 305-day-corrected milk yield serving as the dependent variable. Subsequently, reaction norms were determined utilizing a Random Regression Model. Spearman's correlation was then applied to compare the estimates of breeding values across different environmental gradients for the studied traits. The highest EG (+ 4) indicates the least challenging environments, where animals experience better environmental conditions. Conversely, lower EG (-4) values represent the most challenging environments, where animals endure worse conditions. The only trait that exhibited a moderate heritability magnitude was AFC (0.23) in the least challenging environmental condition. The other traits were classified as having low heritability magnitudes regardless of the evaluated environmental gradient. While minimal evidence was found for the influence of GEI on CI, a clear GEI effect was observed for AFC and AFS across all environmental gradients examined. A reversal in genotype ranking occurred under extreme environmental conditions. The findings suggest that the best-performing genotype under one environmental gradient may not necessarily excel under another.

Pathogenesis of HIV associated nephropathy in children and adolescents: taking a hard look 40 years later in the era of gene-environmental interaction.

HIV-associated nephropathy (HIVAN) is a kidney disease that affects mainly people of African ancestry with a high HIV-1 viral load. New antiretroviral therapies (ART) have been highly efficient preventing and improving the outcome of HIVAN. However, providing chronic ART to children and adolescents living with HIV (CALWH) remains a significant challenge all over the world. More that 2.5 million CALWH, including those living in Sub-Saharan Africa, continue to be at high risk of developing HIVAN. Much of our understanding of the pathogenesis of HIVAN is based on studies conducted in transgenic mice and adults with HIVAN. However, CALWH may experience different health outcomes, risk factors, and susceptibilities to HIVAN in comparison to adults. This article reviews the progress made over the last 40 years in understanding the pathogenesis of HIVAN in CALWH, focusing on how the HIV virus, alongside genetic and environmental factors, contributes to the development of this disease. The landmark discovery that two risks alleles of the Apolipoprotein-1 (APOL1) gene play a critical role in HIVAN has significantly advanced our understanding of the disease's pathogenesis. However, we still need to understand why renal inflammation persists despite ART and determine whether the kidney may harbor HIV reservoirs that need to be eliminated to cure HIV permanently. For these reasons, we emphasize reviewing how HIV-1 infects renal cells, affects their growth and regeneration, and discussing how inflammatory cytokines and APOL1 affect the outcome of childhood HIVAN.

Ethical, Legal, and Social Implications of Gene-Environment Interaction Research.

Many complex disorders are impacted by the interplay of genetic and environmental factors. In gene-environment interactions (GxE), an individual's genetic and epigenetic makeup impacts the response to environmental exposures. Understanding GxE can impact health at the individual, community, and population levels. The rapid expansion of GxE research in biomedical studies for complex diseases raises many unique ethical, legal, and social implications (ELSIs) that have not been extensively explored and addressed. This review article builds on discussions originating from a workshop held by the National Institute of Environmental Health Sciences (NIEHS) and the National Human Genome Research Institute (NHGRI) in January 2022, entitled: "Ethical, Legal, and Social Implications of Gene-Environment Interaction Research." We expand upon multiple key themes to inform broad recommendations and general guidance for addressing some of the most unique and challenging ELSI in GxE research. Key takeaways include strategies and approaches for establishing sustainable community partnerships, incorporating social determinants of health and environmental justice considerations into GxE research, effectively communicating and translating GxE findings, and addressing privacy and discrimination concerns in all GxE research going forward. Additional guidelines, resources, approaches, training, and capacity building are required to further support innovative GxE research and multidisciplinary GxE research teams.

Progeny Selection and Genetic Diversity in a Pinus taeda Clonal Seed Orchard

The present article describes the development of an improved Pinus taeda clonal seed orchard adapted to the edaphoclimatic conditions of Uruguay. Initially, 2068 hectares distributed in nine companies were prospected, and 124 plus trees were identified based on growth, straightness, and health traits. These trees were clonally propagated via grafting to establish a clonal seed orchard. For the genetic evaluation of the orchard, two progeny tests were carried out in the Rivera and Paysandú municipalities. Quantitative genetic analyses allowed us to identify a simple genotype–environment interaction and an expected genetic gain for volumes of 17%, 13%, and 8% for selection intensities of 12%, 25%, and 50%, respectively. Moreover, the genetic diversity of the 124 clones of the orchard was assessed using 10 microsatellite markers. The fingerprinting profiles allowed us to identify a total of 224 alleles. The polymorphism information content of the different markers was in the range of 0.594 to 0.895. The combined probability of identity and probability of identity among siblings had a discrimination power of 8.26 × 10–14 and 5.91 × 10–5, respectively. Analysis of the genetic structure demonstrated that the seed orchard population was not structured by the supplier.

The role of gene–environment interaction in the formation of risk attitudes

Understanding the formation of risk preferences is crucial for elucidating the roots of economic, social, and health inequalities. However, this area remains inadequately explored. This study employs a risk preference measure directly linked to the labor market to examine whether previous experiences with high unemployment rates influence current risk decision-making among the elderly, and whether this impact varies by genotype. The findings indicate that individuals with low genetic predispositions for risk tolerance are more significantly influenced by historical fluctuations in unemployment rates than those with high genetic predispositions for risk tolerance. Consequently, this paper identifies genetic endowment as a crucial moderating factor that shapes how past experiences impact current decision-making processes. This disparity in how past experiences shape risk preferences based on genetic predisposition may further amplify inequalities in health, wealth, income, and other outcomes associated with risk preferences.