A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.
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ABSTRACT:
SUBMITTER: Manning AK
PROVIDER: S-EPMC3613127 | biostudies-literature | 2012 May
REPOSITORIES: biostudies-literature
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Project description:Here we derive candidate gene-environment interaction (GxE) variants from promoter-enhancer interacting regions that respond to dietary fatty acid challenge through altered chromatin accessibility in human primary adipocytes, and demonstrate that molecular genomics data produced in physiologically relevant contexts can illuminate new functional GxE mechanisms in humans and identify variants for GxE testing in large biobanks.
2019-06-17 | GSE129574 | GEO
Project description:ImportanceObesity is associated with a number of noncommunicable chronic diseases and is purported to cause premature death.ObjectiveTo summarize evidence on the temporality of the association between higher body mass index (BMI) and 2 potential mediators: chronic inflammation and hyperinsulinemia.Data sourcesMEDLINE (1946 to August 20, 2019) and Embase (from 1974 to August 19, 2019) were searched, although only studies published in 2018 were included because of a high volume of results. The data analysis was conducted between January 2020 and October 2020.Study selection and measuresLongitudinal studies and randomized clinical trials that measured fasting insulin level and/or an inflammation marker and BMI with at least 3 commensurate time points were selected.Data extraction and synthesisSlopes of these markers were calculated between time points and standardized. Standardized slopes were meta-regressed in later periods (period 2) with standardized slopes in earlier periods (period 1). Evidence-based items potentially indicating risk of bias were assessed.ResultsOf 1865 records, 60 eligible studies with 112 cohorts of 5603 participants were identified. Most standardized slopes were negative, meaning that participants in most studies experienced decreases in BMI, fasting insulin level, and C-reactive protein level. The association between period 1 fasting insulin level and period 2 BMI was positive and significant (β = 0.26; 95% CI, 0.13-0.38; I2 = 79%): for every unit of SD change in period 1 insulin level, there was an ensuing associated change in 0.26 units of SD in period 2 BMI. The association of period 1 fasting insulin level with period 2 BMI remained significant when period 1 C-reactive protein level was added to the model (β = 0.57; 95% CI, 0.27-0.86). In this bivariable model, period 1 C-reactive protein level was not significantly associated with period 2 BMI (β = -0.07; 95% CI, -0.42 to 0.29; I2 = 81%).Conclusions and relevanceIn this meta-analysis, the finding of temporal sequencing (in which changes in fasting insulin level precede changes in weight) is not consistent with the assertion that obesity causes noncommunicable chronic diseases and premature death by increasing levels of fasting insulin.
| S-EPMC7955272 | biostudies-literature
Project description:The genetic regulation of glucose and insulin levels might be modified by adiposity. With regard to the genetic factors that are altered by adiposity, a large meta-analysis on the interactions between genetic variants and body mass index with regard to fasting glucose and insulin levels was reported by the Meta-Analyses of Glucose- and Insulin-related trait Consortium (MAGIC), based on European ancestry. Because no replication study has been performed in other ethnic groups, we first examined the link between reported single-nucleotide polymorphisms (SNPs) and fasting glucose and insulin levels in a large Korean cohort (Korean Genome and Epidemiology Study cohort [KoGES], n = 5,814). The MAGIC study reported 7 novel SNPs for fasting glucose levels and 6 novel SNPs for fasting insulin levels. In this study, we attempted to replicate the association of 5 SNPs with fasting glucose levels and 5 SNPs with fasting insulin levels. One SNP (rs2293941) in PDX1 was identified as a significant obesity-modifiable factor in Koreans. Our results indicate that the novel loci that were identified by MAGIC are poorly replicated in other ethnic groups, although we do not know why.
| S-EPMC4330260 | biostudies-literature
Project description:BackgroundOverweight and obesity is a serious problem worldwide related to cardiovascular and other diseases. Personality traits are associated with the abnormal body mass indices (BMIs) indicative of overweight and obesity. However, the links between personality traits and BMI have been little studied in Korea.MethodsWe evaluated the association between personality traits and BMI in men and women using the rural Ansung and urban Ansan cohort from the Korean Genome Epidemiology Study, and the Kangbuk Samsung Hospital Cohort Study datasets. A shorter version of the original Revised Neuroticism-Extroversion-Openness Personality Inventory (NEO-PI-R) was used to measure the five-factor model of personality (neuroticism, extraversion, openness to experience, agreeableness, and conscientiousness).ResultsData from a total of 1,495 men (mean age 60.0 ± 9.8 years; mean BMI 24.3 ± 3.0 kg/m2) and 2,547 women (mean age 47.0 ± 15.5 years; mean BMI 22.8 ± 3.4 kg/m2) were included in the analysis. Compared with the normal weight groups, overweight and obese men scored higher on openness to experience and lower on conscientiousness. Overweight and obese women scored lower on neuroticism and openness to experience and higher on agreeableness. Extraversion was positively associated with BMI in men (β=0.032, P<0.05). BMI and waist circumference were significantly increased in individuals who were less dutiful. In women, neuroticism was inversely associated with BMI (β=-0.026, P<0.05). Openness to experience was negatively, and agreeableness was positively, associated with BMI (openness to experience: β=-0.072, agreeableness β=0.068) and waist circumference (openness to experience: β=-0.202, agreeableness: β=0.227) (P<0.05).ConclusionPersonality traits were associated with underweight, overweight, and obesity in men and women. Increased understanding of the underlying factors contributing to this association will aid in the prevention and treatment of abnormal BMI.
| S-EPMC3944006 | biostudies-literature
Project description:BackgroundWe investigated the associations of postdiagnostic dietary glycemic index (GI), glycemic load (GL), insulin index (II), and insulin load (IL) with breast cancer-specific and all-cause mortality.MethodsAmong 8,932 women with stage I-III breast cancer identified in the Nurses' Health Study (NHS; 1980-2010) and NHSII (1991-2011), we prospectively evaluated the associations between postdiagnostic GI, GL, II, and IL, and breast cancer-specific and all-cause mortality. Participants completed a validated food frequency questionnaire every 4 years after diagnosis.ResultsDuring follow-up by 2014 in the NHS and 2015 in the NHSII, 2,523 deaths, including 1,071 from breast cancer, were documented. Higher postdiagnostic GL was associated with higher risk of both breast cancer-specific mortality [HRQ5vsQ1 = 1.33; 95% confidence interval (CI) = 1.09-1.63; P trend = 0.008] and all-cause mortality (HRQ5vsQ1 = 1.26; 95% CI = 1.10-1.45; P trend = 0.0006). Higher all-cause mortality was also observed with higher postdiagnostic GI (HRQ5vsQ1 = 1.23; 95% CI = 1.08-1.40; P trend = 0.001), II (HRQ5vsQ1 = 1.20; 95% CI = 1.04-1.38; P trend = 0.005), and IL (HRQ5vsQ1 = 1.23; 95% CI = 1.07-1.42; P trend = 0.0003). The associations were not modified by insulin receptor or estrogen receptor status of the tumor, or body mass index.ConclusionsWe found that higher dietary GL, reflecting postprandial glucose response, after a breast cancer diagnosis was associated with higher risk of breast cancer-specific mortality. Higher dietary GI, GL, II, and IL after a breast cancer diagnosis were associated with higher risk of death from any cause.ImpactThese results suggest that carbohydrate quantity and quality may be important in breast cancer prognosis.See related commentary by McTiernan, p. 252.
| S-EPMC7984717 | biostudies-literature
Project description:ObjectiveThe worldwide prevalence of obesity mandates a widely accessible tool to categorize adiposity that can best predict associated health risks. The body adiposity index (BAI) was designed as a single equation to predict body adiposity in pooled analysis of both genders. We compared body adiposity index (BAI), body mass index (BMI), and other anthropometric measures, including percent body fat (PBF), in their correlations with cardiometabolic risk factors. We also compared BAI with BMI to determine which index is a better predictor of PBF.MethodsThe cohort consisted of 698 Mexican Americans. We calculated correlations of BAI, BMI, and other anthropometric measurements (PBF measured by dual energy X-ray absorptiometry, waist and hip circumference, height, weight) with glucose homeostasis indices (including insulin sensitivity and insulin clearance from euglycemic clamp), lipid parameters, cardiovascular traits (including carotid intima-media thickness), and biomarkers (C-reactive protein, plasminogen activator inhibitor-1 and adiponectin). Correlations between each anthropometric measure and cardiometabolic trait were compared in both sex-pooled and sex-stratified groups.ResultsBMI was associated with all but two measured traits (carotid intima-media thickness and fasting glucose in men), while BAI lacked association with several variables. BAI did not outperform BMI in its associations with any cardiometabolic trait. BAI was correlated more strongly than BMI with PBF in sex-pooled analyses (r?=?0.78 versus r?=?0.51), but not in sex-stratified analyses (men, r?=?0.63 versus r?=?0.79; women, r?=?0.69 versus r?=?0.77). Additionally, PBF showed fewer correlations with cardiometabolic risk factors than BMI. Weight was more strongly correlated than hip with many of the cardiometabolic risk factors examined.ConclusionsBAI is inferior to the widely used BMI as a correlate of the cardiometabolic risk factors studied. Additionally, BMI's relationship with total adiposity may not be the sole determinate of its association with cardiometabolic risk.
| S-EPMC3679008 | biostudies-literature
Project description:Multiple abnormal metabolic traits are found together or "cluster" within individuals more often than is predicted by chance. The individual and combined role of adiposity and insulin resistance (IR) on metabolic trait clustering is uncertain. We tested the hypothesis that change in trait clustering is a function of both baseline level and change in these measures.In 2616 nondiabetic Framingham Offspring Study participants, body mass index (BMI) and fasting insulin were related to a within-person 7-year change in a trait score of 0-4 Adult Treatment Panel III metabolic syndrome traits (hypertension, high triglycerides, low high-density lipoprotein cholesterol, hyperglycemia).At baseline assessment, mean trait score was 1.4 traits, and 7-year mean (SEM) change in trait score was +0.25 (0.02) traits, P<0.0001. In models with BMI predictors only, for every quintile difference in baseline BMI, the 7-year trait score increase was 0.14 traits, and for every quintile increase in BMI during 7-year follow-up, the trait score increased by 0.3 traits. Baseline level and change in fasting insulin were similarly related to trait score change. In models adjusted for age-sex-baseline cluster score, 7-year change in trait score was significantly related to both a 1-quintile difference in baseline BMI (0.07 traits) and fasting insulin (0.18 traits), and to both a 1-quintile 7-year increase in BMI (0.21 traits) and fasting insulin (0.18 traits).Change in metabolic trait clustering was significantly associated with baseline levels and changes in both BMI and fasting insulin, highlighting the importance of both obesity and IR in the clustering of metabolic traits.
| S-EPMC4209491 | biostudies-literature
Project description:Introduction:To study the influence of different glycemic statuses on the relationship of insulin action to age, gender, body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) among Chinese population. Methods:A total of 35,327 participants (17,456 males and 17,871 females) were included in this nationally representative cross-sectional study. Glycemic status was defined according to the 2010 American Diabetes Association criteria. Fasting insulin was measured by the chemiluminescence method. Results:Insulin and HOMA-IR levels were the highest in newly diagnosed diabetes and were lowest in normal fasting glucose (NFG) (P < 0.001). Insulin and HOMA-IR levels were higher in females (P < 0.001) than in males with previously diagnosed diabetes and impaired fasting glucose (IFG) and NFG, meanwhile decreased with age (P < 0.001) among IFG and NFG participants. As compared with participants with a BMI from 18.5 to 19.9, those in the lowest BMI category (<18.5) had a significantly elevated risk of IR (OR, 1.96; 95% CI, 1.01-3.80), as did those in the higher BMI categories among NFG participants. The risk of IR increased with WC and WHtR, and the response was linear (P < 0.001 for linear trend) for the participants with NFG but not in those with IFG. Conclusions:Different glycemic statuses significantly affect the relationships of insulin action to age, gender, BMI, WC, and WHtR among Chinese population.
| S-EPMC6126106 | 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: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