METHODS: Data from four population-based National Health and Morbidity Surveys conducted in 1996, 2006, 2010, and 2015 were pooled. Hierarchical Age-Period-Cohort (HAPC) analysis explored the trajectories of BMI and waist circumference across the life course and birth cohorts by sex and ethnicity. These models assumed no period effect.
RESULTS: Generally, BMI and waist circumference trajectories increased across age and birth cohorts. These trajectories varied by sex and ethnicity. Females have more profound increasing BMI and waist circumference trajectories than their male counterparts as they age and as cohort recency increases. Chinese have less profound BMI and waist circumference increases across the life course and birth cohorts than other ethnic groups.
CONCLUSIONS: The profound increasing cohort trajectories of obesity, regardless of sex and ethnicity, are alarming. Future studies should focus on identifying factors associated with the less profound cohort effect among the Chinese to reduce the magnitude of trajectories in obesity, particularly among future generations.
METHODS: We conducted systematic search in PubMed and Scopus from September 1, 2016, to July 22, 2022. Original COI studies estimating the economic cost of obesity and/or overweight in at least one country, published in English were included. To facilitate the comparison of estimates across countries, we converted the cost estimates of different years to 2022 purchasing power parity (PPP) values using each country's consumer price index (CPI) and PPP conversion rate.
RESULTS: Nineteen studies were included. All studies employed a prevalence-based approach using Population Attributable Fraction (PAF) methodology. About half of the included studies (53%) were conducted in high-income countries while the others (47%) were conducted in middle-income countries. The economic burden of obesity ranged between PPP 15 million in Brazil to PPP 126 billion in the USA, in the year 2022. Direct medical costs accounted for 0.7% to 17.8% of the health system expenditure. Furthermore, the total costs of obesity ranged from 0.05% to 2.42% of the country's gross domestic product (GDP). Of the seven studies that estimated both direct and indirect costs, indirect costs accounted for the largest portion of five studies. Nevertheless, a variety in methodology across studies was identified. The number of co-morbidities included in the analysis varied across studies.
CONCLUSIONS: Although there was a variety of methodologies across studies, consistent evidence indicated that the economic burden of obesity was substantial. Obesity prevention and control should be a public health priority, especially among countries with high prevalence of obesity.
METHODS: Whole-exome sequencing (WES) was carried out on a 15-year-old male proband of Pakistani ancestry who had severe obesity. This was followed by family segregation analysis, using Sanger sequencing. We also undertook re-analysis of WES data from 91 unrelated adults with severe obesity (86% white European ancestry) from the Personalised Medicine for Morbid Obesity (PMMO) cohort, recruited from the UK National Health Service.
RESULTS: We identified an oligogenic mode of inheritance of obesity in the proband's family-this provided the impetus to reanalyze existing sequence data in a separate dataset. Analysis of PMMO participant data revealed two further patients who carried more than one rare, predicted-deleterious mutation in a known monogenic obesity gene. In all three cases, the genes involved had known autosomal dominant inheritance, with incomplete penetrance.
CONCLUSION: Oligogenic inheritance may explain some of the variable penetrance in Mendelian forms of obesity. We caution clinicians and researchers to avoid confining sequence analysis to individual genes and, in particular, not to stop looking when the first potentially-causative mutation is found.
METHODS: Population-based surveys included 30,721 Malay, 10,865 Indian and 25,296 Chinese adults from The Malaysian Cohort, and 413,737 White adults from UK Biobank. Sex-specific linear regression models estimated associations of anthropometry and body composition (body mass index [BMI], waist circumference [WC], fat mass, appendicular lean mass) with systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), triglycerides and HbA1c.
RESULTS: Compared to Malay and Indian participants, Chinese adults had lower BMI and fat mass while White participants were taller with more appendicular lean mass. For BMI and fat mass, positive associations with SBP and HbA1c were strongest among the Chinese and Malay and weaker in White participants. Associations with triglycerides were considerably weaker in those of Indian ethnicity (eg 0.09 [0.02] mmol/L per 5 kg/m2 BMI in men, vs 0.38 [0.02] in Chinese). For appendicular lean mass, there were weak associations among men; but stronger positive associations with SBP, triglycerides, and HbA1c, and inverse associations with LDL-C, among Malay and Indian women. Associations between WC and risk factors were generally strongest in Chinese and weakest in Indian ethnicities, although this pattern was reversed for HbA1c.
CONCLUSION: There were distinct patterns of adiposity and body composition and cardiovascular risk factors across ethnic groups. We need to better understand the mechanisms relating body composition with cardiovascular risk to attenuate the increasing global burden of obesity-related disease.
METHODS: DNA methylation profiles (Illumina Infinium® HumanMethylation450 BeadChip) from 1941 individuals from four population-based European cohorts were analysed in relation to body mass index, waist circumference, waist-hip and waist-height ratio within a meta-analytical framework. In a subset of these individuals, data on genome-wide gene expression level, biomarkers of glucose and lipid metabolism were also available. Validation of methylation markers associated with all adiposity measures was performed in 358 individuals. Finally, we investigated the association of obesity-related methylation marks with breast, colorectal cancer and myocardial infarction within relevant subsets of the discovery population.
RESULTS: We identified 40 CpG loci with methylation levels associated with at least one adiposity measure. Of these, one CpG locus (cg06500161) in ABCG1 was associated with all four adiposity measures (P = 9.07×10-8 to 3.27×10-18) and lower transcriptional activity of the full-length isoform of ABCG1 (P = 6.00×10-7), higher triglyceride levels (P = 5.37×10-9) and higher triglycerides-to-HDL cholesterol ratio (P = 1.03×10-10). Of the 40 informative and obesity-related CpG loci, two (in IL2RB and FGF18) were significantly associated with colorectal cancer (inversely, P