Reverse gene-environment interaction approach to identify variants influencing body mass index in humans
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE129574 | GEO | 2019/06/17
REPOSITORIES: GEO
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Project description:Reverse gene-environment interaction approach to identify variants influencing body mass index in humans
| PRJNA531837 | ENA
Project description:Identifying gene-environment interactions (GxEs) contributing to human cardiometabolic disorders is challenging. Here we apply a reverse GxE candidate search by deriving candidate variants from promoter-enhancer interactions that respond to dietary fatty acid challenge through altered chromatin accessibility in human primary adipocytes. We then test all variants residing in the lipid-responsive open chromatin sites within adipocyte promoter-enhancer contacts for interaction effects between the genotype and dietary saturated fat intake on body mass index (BMI) in the UK Biobank. We discover 14 novel GxE variants in 12 lipid-responsive promoters, including well-known lipid genes (LIPE, CARM1, and PLIN2) and novel genes, such as LDB3, for which we provide further functional and integrative genomics evidence. We further identify 24 GxE variants in enhancers, totaling 38 new GxE variants for BMI in the UK Biobank, demonstrating that molecular genomics data produced in physiologically relevant contexts can discover new functional GxE mechanisms in humans.
| S-EPMC6752726 | biostudies-literature
Project description:Genetic variants in gene regulatory sequences can modify gene expression and mediate the molecular response to environmental stimuli. In addition, genotype–environment interactions (GxE) contribute to complex traits such as cardiovascular disease. Caffeine is the most widely consumed stimulant and is known to produce a vascular response. To investigate GxE for caffeine, we treated vascular endothelial cells with caffeine and used a massively parallel reporter assay to measure allelic effects on gene regulation for over 43,000 genetic variants. We identified 665 variants with allelic effects on gene regulation and 6 variants that regulate the gene expression response to caffeine (GxE, false discovery rate [FDR] < 5%). When overlapping our GxE results with expression quantitative trait loci colocalized with coronary artery disease and hypertension, we dissected their regulatory mechanisms and showed a modulatory role for caffeine. Our results demonstrate that massively parallel reporter assay is a powerful approach to identify and molecularly characterize GxE in the specific context of caffeine consumption.
2024-02-26 | GSE221514 | GEO
Project description:Higher late life body mass index (BMI) is unrelated to or even predicts lower risk of dementia in late life, a phenomenon that may be explained by reverse causation due to weight loss during preclinical phases of dementia. We aim to investigate the association of baseline BMI and changes in BMI with dementia in a large prospective cohort, and to examine whether weight loss predicts cognitive function.Using a national cohort of adults average age 58 years at baseline in 1994 (n=7029), we investigated the associations between baseline BMI in 1994 and memory scores from 2000 to 2010. We also examined the association of BMI change from 1994 to 1998 with memory scores from 2000 to 2010. Last, to investigate reverse causation, we examined whether memory scores in 1996 predicted BMI trajectories from 2000 to 2010.Baseline overweight predicted better memory scores 6 to 16 years later (?=0.012, 95% confidence interval (CI)=0.001; 0.023). Decline in BMI predicted lower memory scores over the subsequent 12 years (?=-0.026, 95% CI= -0.041; -0.011). Lower memory scores at mean age 60 years in 1996 predicted faster annual rate of BMI decline during follow-up (?=-0.158?kg?m(-2) per year, 95% CI= -0.223; -0.094).Consistent with reverse causation, greater decline in BMI over the first 4 years of the study was associated with lower memory scores over the next decade and lower memory scores was associated with a decline in BMI. These findings suggest that preclinical dementia predicts weight loss for people as early as their late 50s.
| S-EPMC4758694 | biostudies-literature
Project description:BACKGROUND:Social relationships have been proposed as a significant factor shaping obesity risk. The first year of college, a period of major social, behavioral, and weight changes, provides a context well-suited to tracking longitudinally the impact of shifting friendships on weight outcomes. This study sought to identify social mechanisms impacting BMI change among emerging adults. METHODS:An analytic sample of 276 college students (71.0% female, 52.2% non-White) provided repeated reports of relationships and BMI was measured up to four times during 2015-2016. Stochastic actor-oriented models were used to examine change in BMI through social influence and change in friendships over time, controlling for sex and race/ethnicity. RESULTS:At baseline, mean BMI was 24.2±4.5 kg/m2. Overall, mean BMI increased over time; individual decreases in BMI were uncommon. There was a selection effect of BMI: participants with BMIs between 22 and 26 kg/m2 were most likely to be nominated as a friend. While participants did not select friends based on BMI similarity, participants who were reported as friends were more likely to experience convergence in BMI over time relative to the BMIs of non-friends (p = 0.015). An increase in BMI (versus stability or a decrease) was more likely for those whose friends had a higher BMI on average compared to participants whose friends had the same or lower BMI (OR = 2.85, 95% CI = 1.22, 6.71). CONCLUSION:Analyses indicated BMI affected friend selection, not through students selecting friends with similar BMI, but rather, by students avoiding friends with more extreme BMI levels.
| S-EPMC6298660 | biostudies-literature
Project description:A dissection of Genotype x Environment interactions in grapevine berry using a multi-layered -omics approach Grapevine, the most widely-cultivated perennial fruit crop, is also considered a very environmentally sensitive crop. It is characterized by remarkable phenotypic plasticity which in turn is believed to effectively buffer environmental extremes especially through transcriptomic and epigenomic reprogramming. Thus, the final phenotype (P) of a given vine is the result of the close interaction between its genetic composition (G) and the environment (E). Here we analyzed Genotype x Environment (GxE) interactions in two grapevine varieties by characterizing their transcriptome plasticity when cultivated in different environments. Specifically, two genotypes (Sangiovese and Cabernet Sauvignon) were cultivated in three different locations in Italy (Bolgheri -littoral Tuscany-, Montalcino – Appennine Tuscany- and Romagna -foothill area-), trained in an almost identical manner, and sampled at four developmental stages over two grapevine growing seasons, 2011 and 2012, for a total of 144 samples that were analyzed by hybridization to a whole-genome microarray and by Reduced Representation Bisulfite Sequencing (RRBS-seq). In order to study the relationships among differential gene expression profiles and environmental cues, we have developed a new statistical data mining tool based on data reduction approaches which allowed a dissection of the transcriptomic data into stage-specific, cultivar-related and GxE important clusters of gene expression. This deep inspection of inner relationships between the different dataset variables allowed the identification of several candidate genes that could represent putative markers of berry quality traits in grapevine GxE interactions. Moreover, the methods used to establish our model provide a framework for the analysis of transcriptome plasticity in other crops as they respond to diverse environments.
2018-04-09 | GSE98762 | GEO
Project description:In public health research, it has been well established that geographic location plays an important role in influencing health outcomes. In recent years, there has been an increased emphasis on the impact of neighborhood or contextual factors as potential risk factors for childhood obesity. Some neighborhood factors relevant to childhood obesity include access to food sources, access to recreational facilities, neighborhood safety, and socioeconomic status (SES) variables. It is common for neighborhood or area-level variables to be available at multiple spatial scales (SS) or geographic units, such as the census block group and census tract, and selection of the spatial scale for area-level variables can be considered as a model selection problem. In this paper, we model the variation in body mass index (BMI) in a study of pediatric patients of the Virginia Commonwealth University (VCU) Medical Center, while considering the selection of spatial scale for a set of neighborhood-level variables available at multiple spatial scales using four recently proposed spatial scale selection algorithms: SS forward stepwise regression, SS incremental forward stagewise regression, SS least angle regression (LARS), and SS lasso. For pediatric BMI, we found evidence of significant positive associations with visit age and black race at the individual level, percent Hispanic white at the census block group level, percent Hispanic black at the census tract level, and percent vacant housing at the census tract level. We also found significant negative associations with population density at the census tract level, median household income at the census tract level, percent renter at the census tract level, and exercise equipment expenditures at the census block group level. The SS algorithms selected covariates at different spatial scales, producing better goodness-of-fit in comparison to traditional models, where all area-level covariates were modeled at the same scale. These findings underscore the importance of considering spatial scale when performing model selection.
| S-EPMC5877018 | biostudies-literature
Project description:Background/objectiveMexico has one of the highest rates of obesity and overweight worldwide, affecting 75% of the population. The country has experienced a dietary and food retail transition involving increased availability of high-calorie-dense foods and beverages. This study aimed to assess the relationship between the retail food environment and body mass index (BMI) in Mexico.Subjects/methodsGeographical and food outlet data were obtained from official statistics; anthropometric measurements and socioeconomic characteristics of adult participants (N = 22,219) came from the nationally representative 2012 National Health and Nutrition Survey (ENSANUT). Densities (store count/census tract area (CTA)) of convenience stores, restaurants, fast-food restaurants, supermarkets and fruit and vegetable stores were calculated. The association of retail food environment variables, sociodemographic data and BMI was tested using multilevel linear regression models.ResultsConvenience store density was high (mean (SD) = 50.0 (36.9)/CTA) compared with other food outlets in Mexico. A unit increase in density of convenience stores was associated with a 0.003 kg/m2 (95% CI: 0.0006, 0.005, p = 0.011) increase in BMI, equivalent to 0.34 kg extra weight for an adult 1.60 m tall for every additional 10% store density increase (number of convenience stores per CTA (km2)). Metropolitan areas showed the highest density of food outlet concentration and the highest associations with BMI (β = 0.01, 95% CI: 0.004-0.01, p < 0.001). A 10% store density increase in these areas would represent a 1 kg increase in weight for an adult 1.60 m tall.ConclusionsConvenience store density was associated with higher mean BMI in Mexican adults. An excessive convenience store availability, that offers unhealthy food options, coupled with low access to healthy food resources or stores retailing healthy food, including fruits and vegetables, may increase the risk of higher BMI. This is the first study to assess the association of the retail food environment and BMI at a national level in Mexico.
| S-EPMC8159738 | biostudies-literature
Project description:ImportanceThe early obesogenic home environment is consistently identified as a key influence on child weight trajectories, but little research has examined the mechanisms of that influence. Such research is essential for the effective prevention and treatment of overweight and obesity.ObjectiveTo test behavioral susceptibility theory's hypothesis that the heritability of body mass index (BMI) is higher among children who live in more obesogenic home environments.Design, setting, and participantsThis study was a gene-environment interaction twin study that used cross-sectional data from 925 families (1850 twins) in the Gemini cohort (a population-based prospective cohort of twins born in England and Wales between March and December 2007). Data were analyzed from July to October 2013 and in June 2018.ExposuresParents completed the Home Environment Interview, a comprehensive measure of the obesogenic home environment in early childhood. Three standardized composite scores were created to capture food, physical activity, and media-related influences in the home; these were summed to create an overall obesogenic risk score. The 4 composite scores were split on the mean, reflecting higher-risk and lower-risk home environments.Main outcomes and measuresQuantitative genetic model fitting was used to estimate heritability of age-adjusted and sex-adjusted BMI (BMI SD score, estimated using British 1990 growth reference data) for children living in lower-risk and higher-risk home environments.ResultsAmong 1850 twins (915 [49.5%] male and 935 [50.5%] female; mean [SD] age, 4.1 [0.4] years), the heritability of BMI SD score was significantly higher among children living in overall higher-risk home environments (86%; 95% CI, 68%-89%) compared with those living in overall lower-risk home environments (39%; 95% CI, 21%-57%). The findings were similar when examining the heritability of BMI in the separate food and physical activity environment domains.Conclusions and relevanceThese findings support the hypothesis that obesity-related genes are more strongly associated with BMI in more obesogenic home environments. Modifying the early home environment to prevent weight gain may be particularly important for children genetically at risk for obesity.
| S-EPMC6396810 | biostudies-literature
Project description:The majority of congenital heart disease cases lack a definitive cause, suggesting the role of gene-environment interactions (GxE) in disease pathogenesis. Maternal diabetes mellitus (matDM) is among the most prevalent environmental risk factors for CHD and matDM associated oxidative stress is known to disrupt cardiac development. Here, we demonstrate that NOTCH1 haploinsufficient endothelial cells have an altered transcriptomic response to oxidative stress compared to control endothelial cells, with an exacerbated effect on gene regulatory networks crucial for endocardial cushion morphogenesis.
2024-10-18 | GSE279323 | GEO