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The interaction between genotype and environment (GEI) significantly influences plant performance, crucial for breeding programs and ultimately boosting crop productivity. Alongside GEI, breeders encounter another hurdle in their quest for yield improvement, notably adverse and negative correlations among pivotal traits. This study delved into the stability of white sugar yield (WSY), root yield (RY), sugar content (SC), extraction coefficient of sugar (ECS), and the interplay among essential traits including RY, SC, alpha amino nitrogen (N), sodium (Na+), and potassium (K+) across 15 sugar beet hybrids and three control varieties. The investigation spanned two locations over two consecutive years (2022-2023), employing a randomized complete block design with four replications to comprehensively analyze these factors. The analysis of variance highlighted the significant effects of environment, genotype, and GEI at the 1% probability level. Notably, the AMMI analysis of GEI revealed the significance of the first component for WSY, RY, and SC, with the first two components proving significant for ECS. Within the linear mixed model (LMM), WSY, RY, SC, and ECS demonstrated significant effects from both genotype and GEI. In the WAASB biplot, genotypes 10, 8, 17, 6, 13, 14, 15, 7, 12, and 16 exhibited stability in WSY, while genotypes 9, 10, 6, 14, 7, 8, 13, 12, 18, and 15 displayed stability in RY. Additionally, genotypes 10, 15, 12, 13, 16, 17, 6, and 14 were stable for SC, and genotypes 8, 10, 7, 6, 13, 12, 16, 17, 15, 14, and 18 showcased stability in ECS, boasting above-average yield values. In the genotype by yield × trait (GYT) biplot, genotypes 15, 18, and 16 emerged as top performers when combining RY with SC, Na+, N, and K+, suggesting their potential for inclusion in breeding programs.
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Beta vulgaris , Genotipo , Fitomejoramiento , Beta vulgaris/genética , Beta vulgaris/crecimiento & desarrollo , Beta vulgaris/metabolismo , Fitomejoramiento/métodos , Interacción Gen-Ambiente , Fenotipo , Raíces de Plantas/genética , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/metabolismo , Potasio/metabolismo , Carácter Cuantitativo Heredable , Azúcares/metabolismo , Nitrógeno/metabolismoRESUMEN
Nitrogen (N) is an important nutrient element needed by cassava for optimum yield and it is a vital component of nucleotides (nucleic acids), enzymes, amino acids (proteins), chlorophyll molecules and hormones, among other essential compounds required for growth and development of cassava. Nitrogen stress is a major cassava production constraint, the study aimed to examine genotype by environment interaction (GEI) effects and fresh root yield stability of 203 diverse cassava clones to identify genotypes with stable performance under low and optimum nitrogen regimes across environments using AMMI and GGE biplot analysis. Experiments were conducted using an augmented block design with three replications for two years in three locations in Nigeria. There were significant differences (p < 0.001) in the genotype's mean performances as well as significant differences (p < 0.001) in the environment's mean performances for all the traits measured in both nitrogen regimes. The AMMI analysis of variance showed significant effects (p < 0.001) for genotypes, environments and the interactions for fresh root yield in both nitrogen regimes. The biplot analysis showed that for fresh root yield in the optimum nitrogen regime, the principal component accounted for 81.54% of the G + GE (Genotype plus and Genotype by Environment) variation. The G + GE for fresh root yield in the low nitrogen regime accounted for a total of 71.64% of the variation. Ten genotypes were identified as the best genotypes under the optimum nitrogen regime, while eleven genotypes were the best under the low nitrogen regime. Three genotypes under optimum nitrogen regimes were high-yielding. Still, they were unstable in their fresh root yield performance across the environments and can be recommended as specifically adapted to the environments they performed best. Three other genotypes were high-yielding genotypes under low nitrogen but were highly unstable in their fresh root yield mean performance across the environments. The environments Otobi_YR1, Igbariam_YR2, and Umudike_YR1 were identified as the most discriminatory among the test environments. The environments Umudike_YR2 and Igbariam_YR1 were identified as the most representative of the test environments and can represent a mega-environment. The best 21 genotypes that performed above the grand mean for fresh root yield in both nitrogen regimes can be further evaluated on the farmer's field for possible advancement.
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Interacción Gen-Ambiente , Genotipo , Manihot , Nitrógeno , Raíces de Plantas , Manihot/genética , Manihot/crecimiento & desarrollo , Manihot/metabolismo , Nitrógeno/metabolismo , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/genética , Raíces de Plantas/metabolismo , NigeriaRESUMEN
Functional hypothalamic amenorrhea (FHA) is a common cause of amenorrhea and chronic anovulation in adolescent girls and young women, diagnosed after excluding other organic causes. It is commonly associated with calorie restriction, excessive physical exercise, and psychosocial stress. These stressors alter the pulsatile secretion of gonadotropin-releasing hormone, leading to a chronic condition of hypoestrogenism and significant health consequences. Recent evidence has highlighted a genetic predisposition to FHA that could explain interindividual variability in stress response. Indeed, not all women experience FHA in response to stress. Rare variants in genes associated with idiopathic hypogonadotropic hypogonadism have been identified in women with FHA, suggesting that these mutations may contribute to an increased susceptibility of women to the trigger of stress exposure. FHA appears today as a complex disease resulting from the combination of genetic predisposition, environmental factors, and epigenetic changes. Furthermore, the genetic background of FHA allows for the hypothesis of a male counterpart. Despite the paucity of data, preliminary findings indicate that an equivalent condition of FHA exists in men, warranting further investigation. This narrative review aims to summarize the recent genetic evidence contributing to the pathophysiology of FHA and to raise awareness on a possible male counterpart.
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Amenorrea , Interacción Gen-Ambiente , Enfermedades Hipotalámicas , Humanos , Amenorrea/genética , Femenino , Enfermedades Hipotalámicas/genética , Predisposición Genética a la Enfermedad , MasculinoRESUMEN
Breastfeeding provides many health benefits, but its impact on respiratory health remains unclear. This study addresses the complex and dynamic nature of the mother-milk-infant triad by investigating maternal genomic factors regulating human milk oligosaccharides (HMOs), and their associations with respiratory health among human milk-fed infants. Nineteen HMOs are quantified from 980 mothers of the CHILD Cohort Study. Genome-wide association studies identify HMO-associated loci on chromosome 19p13.3 and 19q13.33 (lowest P = 2.4e-118), spanning several fucosyltransferase (FUT) genes. We identify novel associations on chromosome 3q27.3 for 6'-sialyllactose (P = 2.2e-9) in the sialyltransferase (ST6GAL1) gene. These, plus additional associations on chromosomes 7q21.32, 7q31.32 and 13q33.3, are replicated in the independent INSPIRE Cohort. Moreover, gene-environment interaction analyses suggest that fucosylated HMOs may modulate overall risk of recurrent wheeze among preschoolers with variable genetic risk scores (P < 0.01). Thus, we report novel genetic factors associated with HMOs, some of which may protect the respiratory health of children.
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Estudio de Asociación del Genoma Completo , Leche Humana , Oligosacáridos , Sialiltransferasas , Humanos , Leche Humana/química , Leche Humana/metabolismo , Femenino , Oligosacáridos/metabolismo , Sialiltransferasas/genética , Sialiltransferasas/metabolismo , Lactante , Masculino , Preescolar , Fucosiltransferasas/genética , Lactancia Materna , Ruidos Respiratorios/genética , Interacción Gen-Ambiente , Polimorfismo de Nucleótido Simple , Adulto , Estudios de Cohortes , Madres , Niño , Cromosomas Humanos Par 3/genética , Lactosa/análogos & derivadosRESUMEN
BACKGROUND: Nonischemic cardiomyopathy (NISCM) is a clinical challenge with limited therapeutic targets. This study aims to identify promising drug targets for NISCM. METHODS: We utilized cis-pQTLs from the deCODE study, which includes data from 35,559 Icelanders, and SNPs from the FinnGen study, which includes data from 1,754 NISCM cases and 340,815 controls of Finnish ancestry. Mendelian randomization (MR) analysis was performed to estimate the causal relationship between circulating plasma protein levels and NISCM risk. Proteins with significant associations underwent false discovery rate (FDR) correction, followed by Bayesian colocalization analysis. The expression of top two proteins, LILRA5 and NELL1, was further analyzed using various NISCM datasets. Descriptions from the Human Protein Atlas (HPA) validated protein expression. The impact of environmental exposures on LILRA5 was assessed using the Comparative Toxicogenomics Database (CTD), and molecular docking identified the potential small molecule interactions. RESULTS: MR analysis identified 255 circulating plasma proteins associated with NISCM, with 16 remaining significant after FDR correction. Bayesian colocalization analysis identified LILRA5 and NELL1 as significant, with PP.H4 > 0.8. LILRA5 has a protective effect (OR = 0.758, 95% CI, 0.670-0.857) while NELL1 displays the risk effect (OR = 1.290, 95% CI, 1.199-1.387) in NISCM. Decreased LILRA5 expression was found in NISCM such as diabetic, hypertrophic, dilated, and inflammatory cardiomyopathy, while NELL1 expression increased in hypertrophic cardiomyopathy. HPA data indicated high LILRA5 expression in neutrophils, macrophages and endothelial cells within normal heart and limited NELL1 expression. Immune infiltration analysis revealed decreased neutrophil in diabetic cardiomyopathy. CTD analysis identified several small molecules that affect LILRA5 mRNA expression. Among these, Estradiol, Estradiol-3-benzoate, Gadodiamide, Topotecan, and Testosterone were found to stably bind to the LILRA5 protein at the conserved VAL-15 or THR-133 residues in the Ig-like C2 domain. CONCLUSION: Based on European Ancestry Cohort, this study reveals that LILRA5 and NELL1 are potential therapeutic targets for NISCM, with LILRA5 showing particularly promising prospects in diabetic cardiomyopathy. Several small molecules interact with LILRA5, implying potential clinical implication.
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Proteínas de Unión al Calcio , Cardiomiopatías , Predisposición Genética a la Enfermedad , Proteínas del Tejido Nervioso , Polimorfismo de Nucleótido Simple , Población Blanca , Humanos , Cardiomiopatías/genética , Cardiomiopatías/metabolismo , Cardiomiopatías/tratamiento farmacológico , Población Blanca/genética , Proteínas de Unión al Calcio/genética , Proteínas de Unión al Calcio/metabolismo , Estudios de Casos y Controles , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Factores de Riesgo , Simulación del Acoplamiento Molecular , Fenotipo , Islandia , Masculino , Femenino , Medición de Riesgo , Persona de Mediana Edad , Teorema de Bayes , Interacción Gen-Ambiente , Terapia Molecular Dirigida , Proteómica , MultiómicaRESUMEN
OBJECTIVES: This study aimed to determine the relative contribution of genetic and environmental factors in the phenotypic variation of the soft tissue facial profile during the mixed dentition and the permanent dentition stages. METHODS: In this retrospective cohort study, standardized facial profile photographs of 139 twin pairs (55 monozygotic and 84 dizygotic) were obtained from archival records at the Adelaide Dental School. Photographic analysis used 12 angular and 14 linear facial profile measurements from the mixed dentition (7-11 years) to the permanent dentition (12-17 years) stages. A genetic analysis was performed using a univariate structural equation model adhering to the normal assumptions of a twin model. RESULTS: In the mixed dentition stage, the additive genetic (A) and unique environment (E) model, AE model, was the most parsimonious in explaining the observed phenotypic variance for all 26 facial traits with the narrow-sense heritability estimates ranging between 0.38 and 0.79. In the permanent dentition, the AE model was the most parsimonious for 20 out of 26 traits, however, the variance of six traits, particularly those in the lower third of the face, was best explained by the shared environmental and unique environmental factors. LIMITATIONS: This study exclusively included twins of European ancestry. CONCLUSIONS: The soft tissue facial profile demonstrated dynamic genetic and environmental influences with a greater additive genetic influence during the mixed dentition and the early stages of the permanent dentition. However, there was evidence of increasing environmental influence in the lower third of the face during the early stages of the permanent dentition.
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Dentición Mixta , Cara , Humanos , Cara/anatomía & histología , Masculino , Niño , Femenino , Adolescente , Estudios Retrospectivos , Gemelos Monocigóticos/genética , Fenotipo , Interacción Gen-Ambiente , Gemelos Dicigóticos/genética , Dentición Permanente , Cefalometría , Desarrollo Maxilofacial/genética , AmbienteRESUMEN
Human mutations of ADNP and ADNP2 are known to be associated with neural developmental disorders (NDDs), including autism spectrum disorders (ASDs) and schizophrenia (SZ). However, the underlying mechanisms remain elusive. In this study, using CRISPR/Cas9 gene editing technology, we generated adnp and adnp2 mutant zebrafish models, which exhibited developmental delays, brain deficits, and core behavioral features of NDDs. RNA sequencing analysis of adnpa-/-; adnpb-/- and adnp2a-/-; adnp2b-/- larval brains revealed altered gene expression profiles affecting synaptic transmission, autophagy, apoptosis, microtubule dynamics, hormone signaling, and circadian rhythm regulation. Validation using whole-mount in situ hybridization (WISH) and real-time quantitative PCR (qRT-PCR) corroborated these findings, supporting the RNA-seq results. Additionally, loss of adnp and adnp2 resulted in significant downregulation of pan-neuronal HuC and neuronal fiber network α-Tubulin signals. Importantly, prolonged low-dose exposure to environmental endocrine disruptors (EEDs) aggravated behavioral abnormalities in adnp and adnp2 mutants. This comprehensive approach enhances our understanding of the complex interplay between genetic mutations and environmental factors in NDDs. Our findings provide novel insights and experimental foundations into the roles of adnp and adnp2 in neurodevelopment and behavioral regulation, offering a framework for future preclinical drug screening aimed at elucidating the pathogenesis of NDDs and related conditions.
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Mutación , Proteínas del Tejido Nervioso , Proteínas de Pez Cebra , Pez Cebra , Animales , Pez Cebra/genética , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Conducta Animal/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Modelos Animales de Enfermedad , Disruptores Endocrinos/toxicidad , Trastorno del Espectro Autista/genética , Sistemas CRISPR-Cas , Interacción Gen-Ambiente , Trastornos del Neurodesarrollo/genética , Trastornos del Neurodesarrollo/inducido químicamente , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismoRESUMEN
BACKGROUND: A genotype-by-environment (G × E) interaction is defined as genotypes responding differently to different environments. In salmonids, G × E interactions can occur in different rearing conditions, including changes in salinity or temperature. However, water flow, an important variable that can influence metabolism, has yet to be considered for potential G × E interactions, although water flows differ across production stages. The salmonid industry is now manipulating flow in tanks to improve welfare and production performance, and expanding sea pen farming offshore, where flow dynamics are substantially greater. Therefore, there is a need to test whether G × E interactions occur under low and higher flow regimes to determine if industry should consider modifying their performance evaluation and selection criteria to account for different flow environments. Here, we used genotype-by-sequencing to create a genomic-relationship matrix of 37 Chinook salmon, Oncorhynchus tshawytscha, families to assess possible G × E interactions for production performance under two flow environments: a low flow regime (0.3 body lengths per second; bl s-1) and a moderate flow regime (0.8 bl s-1). RESULTS: Genetic correlations for the same production performance trait between flow regimes suggest there is minimal evidence of a G × E interaction between the low and moderate flow regimes tested in this study, for Chinook salmon reared from 82.9 ± 16.8 g ( x ¯ ± s.d.) to 583.2 ± 117.1 g ( x ¯ ± s.d.). Estimates of genetic and phenotypic correlations between traits did not reveal any unfavorable trait correlations for size- (weight and condition factor) and growth-related traits, regardless of the flow regime, but did suggest measuring feed intake would be the preferred approach to improve feed efficiency because of the strong correlations between feed intake and feed efficiency, consistent with previous studies. CONCLUSION: This new information suggests that Chinook salmon families do not need to be selected separately for performance across different flow regimes. However, further studies are needed to confirm this across a wider range of fish sizes and flows. This information is key for breeding programs to determine if separate evaluation groups are required for different flow regimes that are used for production (e.g., hatchery, post smolt recirculating aquaculture system, or offshore).
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Interacción Gen-Ambiente , Genotipo , Salmón , Animales , Salmón/genética , FenotipoRESUMEN
OBJECTIVE: We studied gene-environment, as well as gene-gene interaction to elucidate their effects on symptom severity and predict clinical outcomes in functional neurological disorders (FND). METHODS: Eighty-five patients with mixed FND were genotyped for ten single-nucleotide polymorphisms (SNP) from seven different stress-related genes. We tested cross-sectionally the association between genotype and the symptomatology of FND (symptom severity assessed with the examiner-based clinical global impression score [CGI] and age of onset). Clinical outcome was assessed in 52 patients who participated in a follow-up clinical visit after eight months (following their individual therapies as usual). We tested longitudinally the association between genotype and clinical outcome in FND. We examined the contribution of each SNP and their interaction between them to FND symptomatology and outcome. RESULTS: We identified a nominal association between tryptophan hydroxylase 1 (TPH1) rs1800532 and symptom severity (CGI1) in FND under a codominant model (T/T: ßT/T = 2.31, seT/T = 0.57; G/T: ßG/T = -0.18, seG/T = 0.29, P = 0.035), with minor allele (T) carriers presenting more severe symptoms. An association was identified between TPH1 and clinical outcome, suggesting that major allele (G) carriers were more likely to have an improved outcome under a codominant model (G/T: ORG/T = 0.18, CIG/T = [0.02-1.34]; T/T: ORT/T = 2.08, CIT/T = [0.30-14.53], P = 0.041). Our analyses suggested a significant gene-gene interaction for TPH2 (rs4570625) and OXTR (rs2254298) on symptom severity, and a significant gene-gene interaction for TPH1, TPH2 and BDNF (rs1491850) on clinical outcome. CONCLUSION: FND might arise from a complex interplay between individual predisposing risk genes involved in the serotonergic pathway and their gene-gene interactions.
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Enfermedades del Sistema Nervioso , Polimorfismo de Nucleótido Simple , Índice de Severidad de la Enfermedad , Triptófano Hidroxilasa , Humanos , Femenino , Masculino , Triptófano Hidroxilasa/genética , Adulto , Polimorfismo de Nucleótido Simple/genética , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/genética , Interacción Gen-Ambiente , Estudios Transversales , Genotipo , AncianoRESUMEN
Despite its devastating human cost, the rapid spread and global establishment of the severe acute respiratory syndrome coronavirus (SARS-CoV-2) pandemic had the benefit of providing unique insights into the intricate interplay between genetic, environmental, and socioeconomic factors, which collectively impact susceptibility to infection with SARS-CoV-2. Preceding the implementation of broad vaccination programs and assuming the absence of significant acquired immunity, examining the innate vulnerability to the virus becomes essential. There is indeed considerable heterogeneity observed at both the population and individual levels for various SARS-CoV-2 infection phenotypes, including emergence, progression, and survival from the coronavirus disease 2019 (COVID-19) syndrome. Particularly intriguing is the seemingly milder course of COVID-19 disease reported for the African continent early during the pandemic. This was characterized by significantly lower mortality rates in SARS-CoV-2 patients compared with the European and American continents and globally. We will discuss some of the demographic and socioeconomic factors that may have contributed to these observations. We review the mapped COVID-19 genetic architecture, including the remarkable association of type I interferon as a single protective mechanism and a major determinant of susceptibility. Furthermore, we speculate on potential 'environmental' modulators of penetrance and expressivity of intrinsic vulnerability factors, with a focus on the microbiome and associated metabolomes. Additionally, this review explores the potential immunomodulatory contribution of helminth parasites to the human host immune and inflammatory responses to respiratory viral infections.
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COVID-19 , Interacción Gen-Ambiente , SARS-CoV-2 , Humanos , COVID-19/inmunología , SARS-CoV-2/inmunología , Predisposición Genética a la Enfermedad , Inflamación/inmunología , Interferón Tipo I/metabolismo , Interferón Tipo I/inmunología , Interferón Tipo I/genética , PandemiasRESUMEN
Family-based genome-wide association studies (GWASs) are often claimed to provide an unbiased estimate of the average causal effects (or average treatment effects; ATEs) of alleles, on the basis of an analogy between the random transmission of alleles from parents to children and a randomized controlled trial. We show that this claim does not hold in general. Because Mendelian segregation only randomizes alleles among children of heterozygotes, the effects of alleles in the children of homozygotes are not observable. This feature will matter if an allele has different average effects in the children of homozygotes and heterozygotes, as can arise in the presence of gene-by-environment interactions, gene-by-gene interactions, or differences in linkage disequilibrium patterns. At a single locus, family-based GWAS can be thought of as providing an unbiased estimate of the average effect in the children of heterozygotes (i.e., a local average treatment effect; LATE). This interpretation does not extend to polygenic scores (PGSs), however, because different sets of SNPs are heterozygous in each family. Therefore, other than under specific conditions, the within-family regression slope of a PGS cannot be assumed to provide an unbiased estimate of the LATE for any subset or weighted average of families. In practice, the potential biases of a family-based GWAS are likely smaller than those that can arise from confounding in a standard, population-based GWAS, and so family studies remain important for the dissection of genetic contributions to phenotypic variation. Nonetheless, their causal interpretation is less straightforward than has been widely appreciated.
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Estudio de Asociación del Genoma Completo , Desequilibrio de Ligamiento , Polimorfismo de Nucleótido Simple , Humanos , Estudio de Asociación del Genoma Completo/métodos , Herencia Multifactorial/genética , Modelos Genéticos , Heterocigoto , Alelos , Homocigoto , Familia , Interacción Gen-AmbienteRESUMEN
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. This study leverages an ongoing family study of the genetic determinants of risk for obesity, diabetes, hypertension, hyperlipidemia, and depression in a Mexican American population. Data collected included blood pressure, BMI, hepatic transaminases, HbA1c, depression (BDI-II), acculturation/marginalization (ARSMA-II), and liver health as assessed by elastography. Heritability and genotype-by-environment (G×E) interactions were analyzed, focusing on the marginalization/separation measure of the ARSMA-II. Significant heritabilities were found for traits such as HbA1c (h2 = 0.52), marginalization (h2 = 0.30), AST (h2 = 0.25), ALT (h2 = 0.41), and BMI (h2 = 0.55). Genotype-by-environment interactions were significant for HbA1c, AST/ALT ratio, BDI-II, and CAP, indicating that genetic factors interact with marginalization to influence these traits. This study found that acculturation stress exacerbates the genetic response to chronic illness. These findings underscore the importance of considering G×E interactions in understanding disease susceptibility and may inform targeted interventions for at-risk populations. Further research is warranted to elucidate the underlying molecular pathways and replicate these findings in diverse populations.
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Aculturación , Interacción Gen-Ambiente , Americanos Mexicanos , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/patología , Enfermedad del Hígado Graso no Alcohólico/etnología , Masculino , Femenino , Americanos Mexicanos/genética , Adulto , Persona de Mediana Edad , Enfermedad Crónica , Genotipo , Estrés Psicológico/genética , Predisposición Genética a la Enfermedad , Obesidad/genética , Texas/epidemiologíaRESUMEN
Phthalates (PAEs) are synthetic compounds extensively employed in consumer products. Blood pressure (BP) in children can vary, the degree of visit-to-visit BP variability (VVV) is at least partially independent of BP. The interactions between PAEs exposure, pubertal-related genetic susceptibility and lifestyles on childhood VVV are not investigated. This study utilized data from a cohort collected from Oct 2017-2020 in Xiamen, China. Seven urine PAE metabolites were measured. The long-term VVV was characterized employing the standard deviation (SD) and average real variability. We constructed a genetic risk score (GRS) of pubertal-related genes and healthy lifestyle scores. Exposed to high levels of mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP) (OR=1.43, 95â¯%CI=1.07, 1.92) and mono-2-ethyl-5-oxohexyl phthalate (OR=1.36, 95â¯% CI=1.01, 1.83) was related to increased SBP-SD, and the OR for high SBP-SD related to high GRS was 1.38 (95â¯% CI=1.02, 1.85). Compared to participants who had low GRS and low MEHHP exposure, participants exhibiting high GRS and MEHHP levels were more likely to experience high SBP-SD (OR=2.00, P<0.05). Individuals exhibiting low GRS, low MEHHP levels, and adhering to healthy lifestyles were associated with the least probability of experiencing high SBP-SD (OR=0.31, P<0.05). Increased PAEs exposure could elevate childhood systolic VVV, and exacerbated the adverse impact of pubertal-related genetic susceptibility on the high VVV of SBP; however, healthy lifestyles might alleviate these adverse effects. Promoting healthy lifestyles and reducing PAEs exposure for preventing elevated BP variability among children is important, especially for individuals with greater genetic susceptibility to early pubertal onset. ENVIRONMENTAL IMPLICATION: Blood pressure (BP) in children can vary, as a noninvasive, inexpensive and applicable method, the extent of visit-to-visit variability (VVV) is at least partially independent of BP. The interactions between phthalates (PAEs) exposure, variants of puberty-related genes and lifestyles on VVV are not investigated. Increased childhood systolic VVV might be associated with PAEs exposure, with the associations more pronounced combined with pubertal genetic susceptibility. Yet, healthy habits could partly eliminate such adverse effects. Our study underscores the importance of advocating for healthy lifestyles and reducing exposure to PAEs, especially among individuals with high genetic susceptibility to early puberty onset.
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Presión Sanguínea , Exposición a Riesgos Ambientales , Interacción Gen-Ambiente , Estilo de Vida , Ácidos Ftálicos , Humanos , Ácidos Ftálicos/orina , Niño , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/genética , Masculino , Femenino , China , Contaminantes Ambientales/orina , Polimorfismo Genético , Pubertad/efectos de los fármacos , Pubertad/genética , Adolescente , Dietilhexil Ftalato/toxicidad , Estudios de CohortesRESUMEN
Network analysis has become a crucial tool in genetic research, enabling the exploration of associations between genes and diseases. Its utility extends beyond genetics to include the assessment of environmental factors. Unipartite network analysis is commonly used in genomics to visualize initial insights and relationships among variables. Syndromic diseases, such as metabolic syndrome, are characterized by the simultaneous occurrence of various signs, symptoms, and clinicopathological features. Metabolic syndrome encompasses hypertension, diabetes, obesity, and dyslipidemia, and both genetic and environmental factors contribute to its development. Given that relevant data often consist of distinct sets of variables, a more intuitive visualization method is needed. This study applied multipartite network analysis as an effective method to understand the associations among genetic, environmental, and disease components in syndromic diseases. We considered three distinct variable sets: genetic factors, environmental factors, and disease components. The process involved projecting a tripartite network onto a two-mode bipartite network and then simplifying it into a one-mode network. This approach facilitated the visualization of relationships among factors across different sets and within individual sets. To transition from multipartite to unipartite networks, we suggest both sequential and concurrent projection methods. Data from the Korean Association Resource (KARE) project were utilized, including 352,228 SNPs from 8840 individuals, alongside information on environmental factors such as lifestyle, dietary, and socioeconomic factors. The single-SNP analysis step filtered SNPs, supplemented by reference SNPs reported in a genome-wide association study catalog. The resulting network patterns differed significantly by sex: demographic factors and fat intake were crucial for women, while alcohol consumption was central for men. Indirect relationships were identified through projected bipartite networks, revealing that SNPs such as rs4244457, rs2156552, and rs10899345 had lifestyle interactions on metabolic components. Our approach offers several advantages: it simplifies the visualization of complex relationships among different datasets, identifies environmental interactions, and provides insights into SNP clusters sharing common environmental factors and metabolic components. This framework provides a comprehensive approach to elucidate the mechanisms underlying complex diseases like metabolic syndrome.
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Síndrome Metabólico , Polimorfismo de Nucleótido Simple , Humanos , Síndrome Metabólico/genética , Síndrome Metabólico/epidemiología , República de Corea/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Interacción Gen-Ambiente , Adulto , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Redes Reguladoras de Genes , AncianoRESUMEN
According to various research, the risk of multiple sclerosis (MS) is strongly influenced by genetic variations. Population, familial, and molecular studies provide strong empirical support for a polygenic pattern of inheritance, mainly due to relatively common allelic variants in the general population. The strongest MS susceptibility locus, which was unmistakably identified in tested populations, is the major histocompatibility complex on chromosome 6p21.3. However, the effect of a given predisposing variant remains modest, so there is the possibility that multiple gene-gene and/or gene-environment interactions could significantly increase the contribution of specific variants to the overall genetic risk. Furthermore, as is known, susceptibility genes can be subject to epigenetic modifications, which greatly increase the complexity of MS heritability. Investigating epigenetic and environmental factors can provide new opportunities for the molecular basis of the MS, which shows complicated pathogenesis. Although studies of epigenetic changes in MS only began in the last decade, a growing body of literature suggests that these may be involved in the development of MS. Here, we summarize recent studies regarding epigenetic changes related to MS initiation and progression. Furthermore, we discuss how current studies address important clinical questions and how future studies could be used in clinical practice.
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Epigénesis Genética , Predisposición Genética a la Enfermedad , Esclerosis Múltiple , Humanos , Esclerosis Múltiple/genética , Metilación de ADN , Interacción Gen-Ambiente , AnimalesRESUMEN
Purpose: Keratoconus (KC), characterized by progressive corneal protrusion and thinning, is a complex disease influenced by the combination of genetic and environmental factors. The purpose of this study was to explore potential geneâenvironment interaction between the calpastatin (CAST) gene and eye-rubbing in KC. Methods: A case-only study including 930 patients (676 patients with eye-rubbing and 254 patients without eye-rubbing) from the Chinese Keratoconus (CKC) cohort study was performed in the present study. Genotyping of single nucleotide polymorphism (SNP) was conducted using the Illumina Infinium Human Asian Screening Array (ASA) Beadchip. The geneâenvironment interactions between CAST gene and eye-rubbing were analyzed using PLINK version 1.90. The interactions between CAST genotypes and eye-rubbing were analyzed by logistic regression models. The SNP-SNP-environment interactions were analyzed using generalized multifactor dimensionality reduction (GMDR). Results: Three SNPs in CAST gene, namely, rs26515, rs27991, and rs9314177, reached the significance threshold for interactions (defined as P < 2.272 × 10-3). Notably, the minor alleles of these three SNPs exhibited negative interactions with eye-rubbing in KC. The results of logistic regression models revealed that the minor allele homozygotes and heterozygotes of rs26515, rs27991, and rs9314177 also exhibited negative interactions with eye-rubbing. Furthermore, GMDR analysis revealed the significant SNP-SNP-environment interactions among rs26515, rs27991, rs9314177, and eye-rubbing in KC. Conclusions: This study identified rs26515, rs27991, and rs9314177 in CAST gene existed gene-environment interactions with eye-rubbing in KC, which is highly important for understanding the underlying biological mechanisms of KC and guiding precision prevention and proper management.
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Interacción Gen-Ambiente , Genotipo , Queratocono , Polimorfismo de Nucleótido Simple , Humanos , Queratocono/genética , Masculino , Femenino , Adulto , China/epidemiología , Pueblo Asiatico/genética , Proteínas de Unión al Calcio/genética , Adulto Joven , Predisposición Genética a la Enfermedad , Persona de Mediana Edad , Pueblos del Este de AsiaRESUMEN
Background: Genetic and environmental factors contribute to psoriasis, but the impact of residential environments on this condition remains uncertain. We aimed to investigate the association of residential environments with psoriasis risk and explore its interaction with genes. Methods: We retrieved data on the spatial distribution of residential environments at 300 and 1000 m buffer zones from the UK Biobank, including the proportions of natural environments, domestic gardens, green spaces, and blue spaces within these zones. We then used Cox hazard models to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between residential environments and psoriasis risk. Lastly, we constructed polygenic risk scores to determine genetic susceptibility and further analyse the interaction with residential environments. Results: Overall, 3755 incident cases of psoriasis were documented during a median follow-up of 12.45 years. Compared with the lowest exposure quantile (Q1), Q4 exposure to natural environments (1000 m buffer: HR = 1.16, 95% CI = 1.05-1.29; 300 m buffer: HR = 1.12, 95% CI = 1.02-1.24) and green spaces (1000 m buffer: HR = 1.16, 95% CI = 1.04-1.28; 300m buffer: HR = 1.10, 95% CI = 1.00-1.21) increased the risk of psoriasis, while Q4 exposure to domestic gardens (1000 m buffer: HR = 0.85, 95% CI = 0.77-0.93; 300m buffer: HR = 0.91, 95% CI = 0.83-1.00) and Q3 exposure to blue spaces (1000 m buffer: HR = 0.89, 95% CI = 0.81-0.98) were negatively associated with psoriasis risk. Among participants with a high genetic risk, those exposed to high levels of natural environments (1000 m buffer: HR = 1.49, 95% CI = 1.15-1.93; 300 m buffer: HR = 1.39, 95% CI = 1.10-1.77) and green spaces (300 m buffer: HR = 1.30, 95% CI = 1.04-1.64) had a higher risk of psoriasis, while those exposed to blue spaces (1000 m buffer: HR = 0.78, 95% CI = 0.63-0.98) had a lower risk of psoriasis. We also observed joint effects of genetic risk and residential environments and an antagonistic additive interaction between blue spaces and genetic risk (P = 0.011). Conclusions: We observed that residing in natural environments and green areas increased the risk of psoriasis in our sample, while proximity to blue spaces and domestic gardens was associated to reduced risks. The association of residential environments with psoriasis risk was modified by genetic susceptibility.
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Predisposición Genética a la Enfermedad , Psoriasis , Características de la Residencia , Humanos , Psoriasis/genética , Psoriasis/epidemiología , Masculino , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Adulto , Reino Unido/epidemiología , Anciano , Análisis Espacial , Ambiente , Factores de Riesgo , Interacción Gen-AmbienteRESUMEN
Understanding the genotype-by-environment interaction (GEI) and considering it in the selection process is a sine qua non condition for the expansion of Brazilian eucalyptus silviculture. This study's objective is to select high-performance and stable eucalyptus clones based on a novel selection index that considers the Factor Analytic Selection Tools (FAST) and the clone's reliability. The investigation explores the nuances interplay of GEI and extends its insights by scrutinizing the relationship between latent factors and real environmental features. The analysis, conducted across seven trials in five Brazilian states involving 78 clones, employs FAST. The clonal selection was performed using an extended FAST index weighted by the clone's reliability. Further insights about GEI emerge from the integration of factor loadings with 25 environmental features through a principal component analysis. Ten clones, distinguished by high performance, stability, and reliability, have been selected across the target population of environments. The environmental features most closely associated with factor loadings, encompassing air temperature, radiation, and soil characteristics, emerge as pivotal drivers of GEI within this dataset. This study contributes insights to eucalyptus breeders, equipping them to enhance decision-making by harnessing a holistic understanding-from the genotypes under evaluation to the diverse environments anticipated in commercial plantations.
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Eucalyptus , Fitomejoramiento , Eucalyptus/genética , Fitomejoramiento/métodos , Brasil , Interacción Gen-Ambiente , Toma de Decisiones , Genotipo , Ambiente , Reproducibilidad de los ResultadosRESUMEN
This study aims to estimate the familial risks of pterygium and assess its relative contributions to environmental and genetic factors using the 2000-2017 Taiwan National Health Insurance Research Database. The marginal Cox's model and the polygenic liability model were made. In Taiwan, the prevalence rate of pterygium in 2017 was 1.64% for individuals with affected first-degree relatives, higher than the general population (1.34%). The adjusted relative risk (RR) for pterygium was highest for twins of the same sex (15.54), followed by siblings of the same sex (4.69), offsprings (3.39), siblings of the different sex (2.88), spouse (2.12), parents (1.86), twins of the different sex (1.57), respectively. The phenotypic variance of pterygium was 21.6% from additive genetic variance, 24.3% from common environmental factors shared by family members, and 54.1% from non-shared environmental factors, respectively. Sensitivity analysis by restricting those with surgical pterygium reveals that aRRs and the three components were similar to those of the overall pterygium. In summary, the prevalence rate of pterygium was higher for individuals with affected first-degree relatives than for the general population. The non-shared environmental factors account for half of the phenotypic variance of pterygium; genetic and shared environmental factors explain the rest.
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Predisposición Genética a la Enfermedad , Pterigion , Humanos , Pterigion/genética , Pterigion/epidemiología , Taiwán/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Prevalencia , Adulto , Anciano , Factores de Riesgo , Interacción Gen-Ambiente , AmbienteRESUMEN
OBJECTIVE: Neuroticism was found to be associated with cerebral small vessel disease (CSVD) in observational studies. We aimed to explore the causal relationship between distinct components of neuroticism and CSVD. METHODS: Two-sample mendelian randomization (MR) study was conducted to explore the bidirectional causal relationships between three genetically distinct subclusters of neuroticism (depressed affect, worry, and sensitivity to environmental stress and adversity [SESA]) and MRI markers of CSVD using publicly available genome-wide association studies (GWAS) data. Inverse variance weighted (IVW) method was used for the primary causal estimates. Alternative MR approaches and extensive sensitivity analyses were conducted to ensure the robustness of the findings. Multivariable MR (MVMR) analysis was used to estimate the direct causal effects with adjustment of other known risk factors for CSVD. RESULTS: Genetically determined SESA was significantly associated with reduced fractional anisotropy (FA) (beta: -1.94, 95%CI: -3.04 to -0.84, p=5.29e-4), and associated with increased mean diffusivity (MD) (beta=1.55, 95%CI: 0.29 to 2.81, p=0.016) and white matter hyperintensities (WMH) (beta=0.25, 95% CI: 0.03 to 0.47, p=0.029) at the nominally significant level. MVMR analysis suggested the significant associations remained significant after accounting for body mass index (BMI), smoking, alcohol drinking, type 2 diabetes (T2D), hypertension, and depression. The other two neuroticism subclusters (depressed affect and worry) didn't have significant causal effects on the MRI markers. In the reverse MR analysis with the MRI markers as exposures, no significant associations were found. CONCLUSION: This study supported the casual role of SESA in the development of CSVD. Further research to explore the underlying mechanism are warranted.