BMI, All-Cause and Cause-Specific Mortality in Chinese Singaporean Men and Women: The Singapore Chinese Health Study

Background: The optimal range of relative weight for morbidity and mortality in Asian populations is an important question in need of more thorough investigation, especially as obesity rates increase. We aimed to examine the association between body mass index (BMI), all cause and cause-specific mortality to determine the optimal range of BMI in relation to mortality in Chinese men and women in Singapore. Methodology/Principal Findings: We analyzed data from a prospective cohort study of 51,251 middle-aged or older (45– 74) Chinese men and women in the Singapore Chinese Health Study. Participants were enrolled and data on body weight and covariates were collected in 1993–1998 and participants were followed through 2008. The analysis accounted for potential methodological issues through stratification on smoking and age, thorough adjustment of demographic and lifestyle confounders and exclusion of deaths early in the follow-up. Conclusions/Significance: Increased risk of mortality was apparent in underweight (,18.5) and obese BMI categories ($27.5) independent of age and smoking. Regardless of age or BMI, smoking considerably increased the rate of mortality and modified the association between BMI and mortality. The most favorable range of BMI for mortality rates and risk in non-smoking persons below age 65 was 18.5–21.4 kg/m 2, and for non-smoking persons aged 65 and above was 21.5

Microbiota‐Dependent Metabolite Trimethylamine N‐Oxide and Coronary Artery Calcium in the Coronary Artery Risk Development in Young Adults Study (CARDIA)

BACKGROUND: Clinical studies implicate trimethylamine N-oxide (TMAO; a gut microbiota-dependent nutrient metabolite) in cardiovascular disease risk. There is a lack of population-based data on the role of TMAO in advancing early atherosclerotic disease. We tested the prospective associations between TMAO and coronary artery calcium (CAC) and carotid intima-media thickness (cIMT). METHODS AND RESULTS: Data were from the Coronary Artery Risk Development in Young Adults Study (CARDIA), a biracial cohort of US adults recruited in 1985-1986 (n=5115). We randomly sampled 817 participants (aged 33-55 years) who attended examinations in 2000-2001, 2005-2006, and 2010-2011, at which CAC was measured by computed tomography and cIMT (2005-2006) by ultrasound. TMAO was quantified using liquid chromotography mass spectrometry on plasma collected in 2000-2001. Outcomes were incident CAC, defined as Agatston units=0 in 2000-2001 and >0 over 10-year follow-up, CAC progression (any increase over 10-year follow-up), and continuous cIMT. Over the study period, 25% (n=184) of those free of CAC in 2000-2001 (n=746) developed detectable CAC. In 2000-2001, median (interquartile range) TMAO was 2.6 (1.8-4.2) μmol/L. In multivariable-adjusted models, TMAO was not associated with 10-year CAC incidence (rate ratio=1.03; 95% CI: 0.71-1.52) or CAC progression (0.97; 0.68-1.38) in Poisson regression, or cIMT (beta coefficient: -0.009; -0.03 to 0.01) in linear regression, comparing the fourth to the first quartiles of TMAO. CONCLUSIONS: In this population-based study, TMAO was not associated with measures of atherosclerosis: CAC incidence, CAC progression, or cIMT. These data indicate that TMAO may not contribute significantly to advancing early atherosclerotic disease risk among healthy early-middle-aged adults

Public Health Education in India and China:History, Opportunities, and Challenges

Abstract Public health education in China and India has a long history that has been both deeply responsive to the unique needs and medical traditions of each country, and sensitive to global influences. The history of public health education in China reaches back several centuries, with substantial input from American and European organizations during the Republican Era, 1911–1949. In India, centuries-old health care traditions were influenced during the colonial period by the British Empire prior to independence in 1947. Political upheaval in both countries during the 1940s further impacted the public health systems as well as public health education. The primary goal of this review is to outline public health education in India and Mainland China, with a focus on describing the historical systems and structures that have promoted the development of formalized public health education. We examine current challenges, and analyze opportunities for improvement. Health reforms in China and India need to consider new and modern models for public health education, perhaps in independent faculties of public health, to reinvigorate public health education and strengthen the position of public health in addressing the health challenges of the 21st century

Polymorphisms in the ICAM1 gene predict circulating soluble intercellular adhesion molecule-1(sICAM-1)

Polymorphisms within the ICAM1 structural gene have been shown to influence circulating levels of soluble intercellular adhesion molecule -1 (sICAM-1) but their relation to atherosclerosis has not been clearly established. We sought to determine whether ICAM1 SNPs are associated with circulating sICAM-1 concentration, coronary artery calcium (CAC), and common and internal carotid intima medial thickness (IMT)

Race and Vitamin D Binding Protein Gene Polymorphisms Modify the Association of 25-Hydroxyvitamin D and Incident Heart Failure: The ARIC (Atherosclerosis Risk in Communities) Study

Abstract Objectives This study sought to determine if low serum 25-hydroxyvitamin D (25[OH]D) is associated with incident heart failure (HF) and if the association is: 1) partly mediated by traditional cardiovascular risk factors; 2) stronger among whites than blacks; and 3) stronger among those genetically predisposed to having high levels of vitamin D binding protein (DBP).Background Suboptimal 25(OH)D is a potential cardiovascular risk factor.Methods A total of 12,215 ARIC (Atherosclerosis Risk in Communities) study participants free of HF at baseline (1990 to 1992; median age, 56; 24% black) were followed through 2010. Total serum 25(OH)D was measured at baseline using liquid chromatography–mass spectrometry. Incident HF events were identified by a hospital discharge code of ICD9-428 and parallel International Classification of Diseases codes for HF deaths.Results During 21 years of follow-up, 1,799 incident HF events accrued. The association between 25(OH)D and HF varied by race (p-interaction = 0.02). Among whites, risk was 2-fold higher for those in the lowest (≤17 ng/ml) versus highest (≥31 ng/ml) quintile of 25(OH)D. The association was attenuated but remained significant with covariate adjustment. In blacks there was no overall association. In both races, those with low 25(OH)D and the rs7041 G allele, which predisposes to high DBP, were at greater risk (p-interaction = 0.01).Conclusions Low serum 25(OH)D was independently associated with incident HF among whites, but not among blacks. However, in both races, low 25(OH)D was associated with HF risk among those genetically predisposed to high DBP. These findings provide novel insight into metabolic differences that may underlie racial variation in the association between 25(OH)D and cardiovascular risk

Common Coding Variants of the HNF1A Gene Are Associated With Multiple Cardiovascular Risk Phenotypes in Community-Based Samples of Younger and Older European-American Adults: The Coronary Artery Risk Development in Young Adults Study and The Cardiovascular Health Study

The transcription factor hepatocyte nuclear factor 1 (HNF-1) α regulates the activity of a number of genes involved in innate immunity, blood coagulation, lipid and glucose transport and metabolism, and cellular detoxification. Common polymorphisms of the HNF-1α gene (HNF1A) were recently associated with plasma C-reactive protein (CRP) and gamma-glutamyl transferase (GGT) concentration in middle-aged to older European-Americans (EA)

The Influence of Obesity-Related Single Nucleotide Polymorphisms on BMI Across the Life Course: The PAGE Study

Evidence is limited as to whether heritable risk of obesity varies throughout adulthood. Among >34,000 European Americans, aged 18–100 years, from multiple U.S. studies in the Population Architecture using Genomics and Epidemiology (PAGE) Consortium, we examined evidence for heterogeneity in the associations of five established obesity risk variants (near FTO, GNPDA2, MTCH2, TMEM18, and NEGR1) with BMI across four distinct epochs of adulthood: 1) young adulthood (ages 18–25 years), adulthood (ages 26–49 years), middle-age adulthood (ages 50–69 years), and older adulthood (ages ≥70 years); or 2) by menopausal status in women and stratification by age 50 years in men. Summary-effect estimates from each meta-analysis were compared for heterogeneity across the life epochs. We found heterogeneity in the association of the FTO (rs8050136) variant with BMI across the four adulthood epochs (P = 0.0006), with larger effects in young adults relative to older adults (β [SE] = 1.17 [0.45] vs. 0.09 [0.09] kg/m2, respectively, per A allele) and smaller intermediate effects. We found no evidence for heterogeneity in the association of GNPDA2, MTCH2, TMEM18, and NEGR1 with BMI across adulthood. Genetic predisposition to obesity may have greater effects on body weight in young compared with older adulthood for FTO, suggesting changes by age, generation, or secular trends. Future research should compare and contrast our findings with results using longitudinal data

Rare variant associations with waist-to-hip ratio in European-American and African-American women from the NHLBI-Exome Sequencing Project

Waist-to-hip ratio (WHR), a relative comparison of waist and hip circumferences, is an easily accessible measurement of body fat distribution, in particular central abdominal fat. A high WHR indicates more intra-abdominal fat deposition and is an established risk factor for cardiovascular disease and type 2 diabetes. Recent genome-wide association studies have identified numerous common genetic loci influencing WHR, but the contributions of rare variants have not been previously reported. We investigated rare variant associations with WHR in 1510 European-American and 1186 African-American women from the National Heart, Lung, and Blood Institute-Exome Sequencing Project. Association analysis was performed on the gene level using several rare variant association methods. The strongest association was observed for rare variants in IKBKB (P=4.0 × 10−8) in European-Americans, where rare variants in this gene are predicted to decrease WHRs. The activation of the IKBKB gene is involved in inflammatory processes and insulin resistance, which may affect normal food intake and body weight and shape. Meanwhile, aggregation of rare variants in COBLL1, previously found to harbor common variants associated with WHR and fasting insulin, were nominally associated (P=2.23 × 10−4) with higher WHR in European-Americans. However, these significant results are not shared between African-Americans and European-Americans that may be due to differences in the allelic architecture of the two populations and the small sample sizes. Our study indicates that the combined effect of rare variants contribute to the inter-individual variation in fat distribution through the regulation of insulin response

Transethnic insight into the genetics of glycaemic traits: fine-mapping results from the Population Architecture using Genomics and Epidemiology (PAGE) consortium

AIMS/HYPOTHESIS: Elevated levels of fasting glucose and fasting insulin in non-diabetic individuals are markers of dysregulation of glucose metabolism and are strong risk factors for type 2 diabetes. Genome-wide association studies have discovered over 50 SNPs associated with these traits. Most of these loci were discovered in European populations and have not been tested in a well-powered multi-ethnic study. We hypothesised that a large, ancestrally diverse, fine-mapping genetic study of glycaemic traits would identify novel and population-specific associations that were previously undetectable by European-centric studies. METHODS: A multiethnic study of up to 26,760 unrelated individuals without diabetes, of predominantly Hispanic/Latino and African ancestries, were genotyped using the Metabochip. Transethnic meta-analysis of racial/ethnic-specific linear regression analyses were performed for fasting glucose and fasting insulin. We attempted to replicate 39 fasting glucose and 17 fasting insulin loci. Genetic fine-mapping was performed through sequential conditional analyses in 15 regions that included both the initially reported SNP association(s) and denser coverage of SNP markers. In addition, Metabochip-wide analyses were performed to discover novel fasting glucose and fasting insulin loci. The most significant SNP associations were further examined using bioinformatic functional annotation. RESULTS: Previously reported SNP associations were significantly replicated (p ≤ 0.05) in 31/39 fasting glucose loci and 14/17 fasting insulin loci. Eleven glycaemic trait loci were refined to a smaller list of potentially causal variants through transethnic meta-analysis. Stepwise conditional analysis identified two loci with independent secondary signals (G6PC2-rs477224 and GCK-rs2908290), which had not previously been reported. Population-specific conditional analyses identified an independent signal in G6PC2 tagged by the rare variant rs77719485 in African ancestry. Further Metabochip-wide analysis uncovered one novel fasting insulin locus at SLC17A2-rs75862513. CONCLUSIONS/INTERPRETATION: These findings suggest that while glycaemic trait loci often have generalisable effects across the studied populations, transethnic genetic studies help to prioritise likely functional SNPs, identify novel associations that may be population-specific and in turn have the potential to influence screening efforts or therapeutic discoveries. DATA AVAILABILITY: The summary statistics from each of the ancestry-specific and transethnic (combined ancestry) results can be found under the PAGE study on dbGaP here: https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000356.v1.p1