Explore the vast range of titles available.

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci ( P  < 5 × 10 −8 ), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis. A genome-wide association study and Metabochip meta-analysis of body mass index (BMI) detects 97 BMI-associated loci, of which 56 were novel, and many loci have effects on other metabolic phenotypes; pathway analyses implicate the central nervous system in obesity susceptibility and new pathways such as those related to synaptic function, energy metabolism, lipid biology and adipogenesis. Genetic correlates of obesity In the second of two Articles in this issue from the GIANT Consortium, Elizabeth Speliotes and collegues conducted a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), commonly used to define obesity and assess adiposity, to find 97 BMI-associated loci, of which 56 were novel. Many of these loci have significant effects on other metabolic phenotypes. The 97 loci account for about 2.7% of BMI variation, and genome-wide estimates suggest common variation accounts for more than 20% of BMI variation. Pathway analyses implicate the central nervous system in obesity susceptibility including synaptic function, glutamate signaling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

A large-scale epigenome-wide association study identifies changes in DNA methylation associated with body mass index in blood and adipose tissue, and correlates DNA methylation sites with high risk of incident type 2 diabetes. Body fat and diabetes risk Obesity is a major risk factor for type 2 diabetes and related metabolic disorders. Genetic association studies have identified genomic loci associated with obesity, and recent studies have also suggested associations with DNA methylation. These authors report an epigenome-wide association study for body mass index (BMI), identifying an association with DNA methylation at 187 loci in blood and adipose tissue. They find that these methylation changes are secondary to adiposity and are also associated with an increased risk of developing type 2 diabetes, independent of conventional risk factors. Approximately 1.5 billion people worldwide are overweight or affected by obesity, and are at risk of developing type 2 diabetes, cardiovascular disease and related metabolic and inflammatory disturbances 1 , 2 . Although the mechanisms linking adiposity to associated clinical conditions are poorly understood, recent studies suggest that adiposity may influence DNA methylation 3 , 4 , 5 , 6 , a key regulator of gene expression and molecular phenotype 7 . Here we use epigenome-wide association to show that body mass index (BMI; a key measure of adiposity) is associated with widespread changes in DNA methylation (187 genetic loci with P  < 1 × 10 −7 , range P  = 9.2 × 10 −8 to 6.0 × 10 −46 ; n  = 10,261 samples). Genetic association analyses demonstrate that the alterations in DNA methylation are predominantly the consequence of adiposity, rather than the cause. We find that methylation loci are enriched for functional genomic features in multiple tissues ( P  < 0.05), and show that sentinel methylation markers identify gene expression signatures at 38 loci ( P  < 9.0 × 10 −6 , range P  = 5.5 × 10 −6 to 6.1 × 10 −35 , n  = 1,785 samples). The methylation loci identify genes involved in lipid and lipoprotein metabolism, substrate transport and inflammatory pathways. Finally, we show that the disturbances in DNA methylation predict future development of type 2 diabetes (relative risk per 1 standard deviation increase in methylation risk score: 2.3 (2.07–2.56); P  = 1.1 × 10 −54 ). Our results provide new insights into the biologic pathways influenced by adiposity, and may enable development of new strategies for prediction and prevention of type 2 diabetes and other adverse clinical consequences of obesity.

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge–purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 ( P =3.01 × 10 −7 ) in SOX2OT and rs17030795 ( P =5.84 × 10 −6 ) in PPP3CA . Two additional signals were specific to Europeans: rs1523921 ( P =5.76 × 10 − 6 ) between CUL3 and FAM124B and rs1886797 ( P =8.05 × 10 − 6 ) near SPATA13 . Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance ( P =4 × 10 −6 ), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.

This longitudinal study sought to identify distinct body mass index (BMI) trajectories and investigate the impact of these level-independent BMI trajectories on the prevalence of thyroid nodules (TN). This study encompassed a cohort of 1967 participants from a hospital in China. Utilizing latent class growth mixture modeling (LCGMM), four BMI trajectory groups were identified based on the BMI of individuals without TN from 2017 to 2019. The occurrence of TN in participants was monitored from 2020 to 2021. BMI trajectory classes and age were considered potential risk factors for TN development. After adjusting for covariates, the odds ratios (ORs) of model-estimated BMI levels were confirmed in the 27-50-year age group, ranging from 1.077 (1.000–1.158) to 1.189 (1.072–1.319). Significant associations between model-estimated BMI slope and TN were observed in the 21-47-year-old age group, with ORs varying between 1.270 (1.014, 1.591) and 2.490 (1.004, 6.174). The level-independent BMI trajectories throughout life significantly influenced the risk of TN prevalence. Moreover, controlling BMI growth rate in early adulthood (27–47 years old) emerged as a critical age window for reducing TN prevalence, underscoring its importance in TN prevention strategies.

•This study surveyed the dynamics of nutritional status based on dietary intake of farm women in the central India state of Madhya Pradesh.•Inequality (estimated by Gini coefficient) analysis found that there is not much variation in the nutrient intake levels across the physical status of the respondents.•Actual intake of nutrients varied significantly across the physical status of the farm women, the physical activities they carried out, and their monthly income level.•The study also suggests a slew of policy options to overcome the nutritional gap in farm women. Nutritional security for women working in agriculture is one of the most serious and persisting concerns in developing countries like India. The present study surveyed the dynamics of nutritional status based on dietary intake, namely calorie, carbohydrate, protein, fat, calcium, folic acid, iron, vitamin, carotene, etc., in the farm women in the central India state of Madhya Pradesh. A total of 225 farm women (ages 18 to 60 y) who were engaged in agricultural activities were selected for this study. The nutritional survey was done by personal interview on food intake with a pretested interview schedule and daily dietary intake. The survey questionnaire includes information on family, socioeconomic status, income, education, occupation, and food habits of the farm women. As \"daily dietary intake\", respondents were asked to list all foods and beverages consumed for a whole day. The mean age, height, weight, and body mass index of the respondents were 34.93 y, 1519 mm, 49.47 kg, and 21.5 kg/m2, respectively. Based on different grades of nutrition, body mass index results indicated that 28% were underweight, 52.4% were normal, 17.8% were overweight, and 1.8% were obese. Inequality (estimated by Gini coefficient) analysis found that there is not much variation in the nutrient intake levels across the physical status of the respondents, with the exception of carotene and vitamin C. The classification and regression tree analysis indicated that with the exception of fat, the rest of the nutrients were not significant in determining the farm women's physical status in terms of weight. In the analysis of the waist-to-hip ratio, the risk of metabolic diseases (cardiovascular disease, diabetes, etc.) was higher in the 31- to 40-y age group. Overall food frequency indicated that poor intake of micronutrients in their diet according to their work activity results in poor health status. The study affirmed that the actual intake of nutrients varied significantly across the physical status of the farm women, their physical activities carried out, and their monthly income level. The study also suggests various policy options to overcome the nutritional gap in farm women.

BackgroundHigher body mass index (BMI) is associated with better outcome compared with normal weight in patients with HF and other chronic diseases. It remains uncertain whether the apparent protective role of obesity relates to the absence of comorbidities. Therefore, we investigated the effect of BMI on outcome in younger patients without co-morbidities as compared to older patients with co-morbidities in a large heart failure (HF) population.MethodsIn an individual patient data analysis from pooled cohorts, 5,819 patients with chronic HF and data available on BMI, co-morbidities and outcome were analysed. Patients were divided into four groups based on BMI (i.e. ≤ 18.5 kg/m2, 18.5–25.0 kg/m2; 25.0–30.0 kg/m2; 30.0 kg/m2). Primary endpoints included all-cause mortality and HF hospitalization-free survival.ResultsMean age was 65 ± 12 years, with a majority of males (78%), ischaemic HF and HF with reduced ejection fraction. Frequency of all-cause mortality or HF hospitalization was significantly worse in the lowest two BMI groups as compared to the other two groups; however, this effect was only seen in patients older than 75 years or having at least one relevant co-morbidity, and not in younger patients with HF only. After including medications and N-terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin concentrations into the model, the prognostic impact of BMI was largely absent even in the elderly group with co-morbidity.ConclusionsThe present study suggests that obesity is a marker of less advanced disease, but does not have an independent protective effect in patients with chronic HF.Graphic abstractCategories of BMI are only predictive of poor outcome in patients aged > 75 years or with at least one co-morbidity (bottom), but not in those aged < 75 years without co-morbidities (top). The prognostic effect largely disappears in multivariable analyses even for the former group. These findings question the protective effect of obesity in chronic heart failure (HF).

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures ( P  < 5 × 10 −8 ). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms. Genome-wide association meta-analyses of waist-to-hip ratio adjusted for body mass index in more than 224,000 individuals identify 49 loci, 33 of which are new and many showing significant sexual dimorphism with a stronger effect in women; pathway analyses implicate adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution. Cardiometabolic traits linked to body fat distribution In the first of a pair of Articles in this issue from the GIANT Consortium, genome-wide association meta-analyses of waist and hip circumference-related traits in more than 200,000 individuals have been used to identify 49 loci — 33 of them new — associated with waist-to-hip ratio adjusted for body mass index and an additional 19 loci associated with related waist and hip circumference measures. A subset of these loci shows significant sexual dimorphism, with many showing a stronger effect in women. Analyses implicate adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms and offer potential targets for interventions in the risks associated with abdominal fat accumulation.

The triglyceride glucose‐body mass index (TyG‐BMI) has been considered an alternative marker of insulin resistance (IR). This cross‐sectional study was designed to mainly investigate the association between TyG‐BMI, triglyceride glucose combined with body mass index, and hypertension in Chinese adults. The relationship between TyG‐BMI and hypertension was examined by multivariate logistic regression and restricted cubic spline model. Multiple logistic regression models were also performed to examine the associations between the individual components of TyG‐BMI (BMI, TyG index, TG and FBG) and hypertension. The incremental ability of TyG‐BMI versus its individual components for hypertension discrimination was evaluated by C‐statistic and net reclassification index. Subgroup analysis was performed to examine potential interactions. A total of 92,545 participants (38.9% men, mean age 53.7 years) were included for final analysis. Logistic regression models showed TyG‐BMI and its individual components were all significantly associated with the odds of hypertension (p for trend < .001). The restricted cubic spline regression manifested a linear association between TyG‐BMI and hypertension (p for non‐linear = .062). The addition of TyG‐BMI, in comparison with each individual component, exhibited the maximum incremental value for the discrimination of hypertension on the basis of base model (C‐statistic: 0.679, 95% CI: 0.675‐0.683 for base model vs. 0.695, 95% CI: 0.691‐0.699 for base model + TyG‐BMI; net reclassification index: 0.226, 95% CI: 0.215‐0.234). TyG‐BMI was significantly associated with the odds of hypertension and can be a better discriminator of hypertension.

A combination of multiple nutritional indexes may more comprehensively and favorably reflect dialysis patient's prognosis. In the present study, we aimed to evaluated the association between total cholesterol/(body mass index × serum albumin) (TC/BA) and mortality in patients with continuous ambulatory peritoneal dialysis (CAPD). We conducted a multicenter retrospective cohort study that included 2907 incident Chinese CAPD patients from seven peritoneal dialysis centers in China between January 1, 2005, and May 31, 2023. The primary outcome was all-cause mortality. We used restricted-cubic-spline plots to explore the shape of the association between TC/BA and outcome. Cause-specific hazard models examined the association between TC/BA and mortality. Of 2907 patients, 754 (25.9%) patients died, including 351 (46.6%) deaths due to cardiovascular disease. A positive linear relationship was observed between TC/BA and all-cause mortality (nonlinear,  = 0.374). In the multivariate cause-specific hazard model, a per-1.0 increase of TC/BA had a 1.29-fold (95% confidence interval [CI] 1.19-1.39) risk of all-cause mortality in the total population. Similar trends were observed in subgroup analyses (all P for interactions > 0.05). Notably, the hazard ratio (HR) of TC/BA (per-1.0 increase) was 1.32 (95% CI 1.23-1.41), 1.29 (95% CI 1.19-1.41), and 1.25 (95% CI 1.22-1.27) times higher than the HR of body mass index (per-1.0 decrease), total cholesterol (per-10 increase), and serum albumin (per-1.0 decrease), respectively. TC/BA was positively linearly related to mortality and may outperform each index in assessing CAPD patient prognosis. The combined nutritional index may more comprehensively and favorably evaluate CAPD patients' prognosis.

ABSTRACT Investigating the association between gestational weight gain (GWG) on low birth weight (LBW, birth weight < 2500 g) across pre‐pregnancy body mass index (BMI) categories (underweight: < 18.5, normal: 18.5–24.9 and overweight/obese: ≥ 25 kg/m²) is crucial for clinical practice. While the Institute of Medicine's (IOM) 2009 GWG guidelines are widely used, evidence‐based data from diverse populations is scarce, creating a global research gap. We explored how total GWG and adherence to IOM recommendations affected the odds of LBW across BMI categories in the Sri Lankan context. This nationwide prospective study evaluated 1499 maternal and singleton‐newborn pairs between August 2022 and April 2024. Unadjusted and adjusted logistic regression analyses were performed. An increase in total GWG z‐score was associated with decreased odds of LBW among women with underweight pre‐pregnancy BMI (aOR: 0.56, 95% CI: 0.35‒0.89), but no significant association was observed among women with normal or ≥ 25 kg/m² BMI. Women with underweight BMI whose GWG was below the IOM recommended range showed higher odds of LBW than those with GWG within the recommended range (aOR 3.05, 95% CI: 1.08‒8.61). However, among women with normal or higher BMI, GWG below the recommended range was not significantly associated with LBW. These findings suggest that the association between GWG and odds of LBW varies across pre‐pregnancy BMI categories. Among Sri Lankan women with underweight pre‐pregnancy BMI, gaining pregnancy weight within the IOM GWG recommendations was associated with significantly lower odds of delivering an LBW newborn. This association was not observed among women with normal or higher BMI. Gestational weight gain below the Institute of Medicine's recommended range was most prevalent among Sri Lankan women with underweight pre‐pregnancy body mass index and was associated with higher odds of low birth weight deliveries. Summary The impact of the Institute of Medicine's gestational weight gain recommendations on adverse birth outcomes in Asian populations is unclear and lacks evidence‐based findings. Pre‐pregnancy body mass index and gestational weight gain impact newborns' birth weight. Gaining pregnancy weight within the IOM‐recommended range was associated with reduced odds of LBW among Sri Lankan women with underweight pre‐pregnancy BMI, whereas no such association was observed among women in other BMI categories.