Discordant Risk: Overweight and cardiometabolic risk in Chinese adults

Recent US work identifies “metabolically healthy overweight” and “metabolically at risk normal weight” individuals. Less is known for modernizing countries with recent increased obesity. Fasting blood samples, anthropometry and blood pressure from 8,233 adults aged 18–98 in the 2009 nationwide China Health and Nutrition Survey, were used to determine prevalence of overweight (Asian cut point, BMI≥23 kg/m2) and five risk factors [pre-diabetes/diabetes (HbA1c≥5.7%) inflammation (hsCRP ≥3 mg/L), pre-hypertension/hypertension (SBP/DBP≥130/85 mmHg), high triglycerides (≥150 mg/dL), low high-density lipoprotein cholesterol (70 years: 73%). Abdominal obesity was highly predictive of metabolic risk, irrespective of overweight (e.g., “metabolically at risk overweight” relative to “metabolically healthy normal weight” [men: Relative Risk Ratio (RRR) =39.06; 95% Confidence Interval (CI): 23.47, 65.00; women: RRR=22.26; 95% CI: 17.49, 28.33]). To conclude, a large proportion of Chinese adults have metabolic abnormalities. High hypertension risk with age, irrespective of obesity underlies the low prevalence of metabolically healthy overweight. Screening for cardiometabolic-related outcomes dependent upon overweight will likely miss a large portion of the Chinese at-risk population

Discordant Risk: Overweight and Cardiometabolic Risk in Chinese Adults

Recent US work identifies “metabolically healthy overweight” and “metabolically at risk normal weight” individuals. Less is known for modernizing countries with recent increased obesity. Fasting blood samples, anthropometry and blood pressure from 8,233 adults aged 18–98 in the 2009 nationwide China Health and Nutrition Survey, were used to determine prevalence of overweight (Asian cut point, BMI≥23 kg/m2) and five risk factors [pre-diabetes/diabetes (HbA1c≥5.7%) inflammation (hsCRP ≥3 mg/L), pre-hypertension/hypertension (SBP/DBP≥130/85 mmHg), high triglycerides (≥150 mg/dL), low high-density lipoprotein cholesterol (70 years: 73%). Abdominal obesity was highly predictive of metabolic risk, irrespective of overweight (e.g., “metabolically at risk overweight” relative to “metabolically healthy normal weight” [men: Relative Risk Ratio (RRR) =39.06; 95% Confidence Interval (CI): 23.47, 65.00; women: RRR=22.26; 95% CI: 17.49, 28.33]). To conclude, a large proportion of Chinese adults have metabolic abnormalities. High hypertension risk with age, irrespective of obesity underlies the low prevalence of metabolically healthy overweight. Screening for cardiometabolic-related outcomes dependent upon overweight will likely miss a large portion of the Chinese at-risk population

Individuals with obesity and COVID-19: A global perspective on the epidemiology and biological relationships

The linkage of individuals with obesity and COVID-19 is controversial and lacks systematic reviews. After a systematic search of the Chinese and English language literature on COVID-19, 75 studies were used to conduct a series of meta-analyses on the relationship of individuals with obesity–COVID-19 over the full spectrum from risk to mortality. A systematic review of the mechanistic pathways for COVID-19 and individuals with obesity is presented. Pooled analysis show individuals with obesity were more at risk for COVID-19 positive, >46.0% higher (OR = 1.46; 95% CI, 1.30–1.65; p < 0.0001); for hospitalization, 113% higher (OR = 2.13; 95% CI, 1.74–2.60; p < 0.0001); for ICU admission, 74% higher (OR = 1.74; 95% CI, 1.46–2.08); and for mortality, 48% increase in deaths (OR = 1.48; 95% CI, 1.22–1.80; p < 0.001). Mechanistic pathways for individuals with obesity are presented in depth for factors linked with COVID-19 risk, severity and their potential for diminished therapeutic and prophylactic treatments among these individuals. Individuals with obesity are linked with large significant increases in morbidity and mortality from COVID-19. There are many mechanisms that jointly explain this impact. A major concern is that vaccines will be less effective for the individuals with obesity

Variant Near FGF5 Has Stronger Effects on Blood Pressure in Chinese With a Higher Body Mass Index

The objective of this study was to investigate the genetic association of 4 candidate variants with blood pressure and test the modifying effects of environmental factors including age, sex, and body mass index (BMI)

Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels

Large-scale meta-analyses of genome-wide association studies (GWAS) have identified >175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P < 5 × 10-8) three novel loci associated with HDL-C near CD163-APOBEC1 (P = 7.4 × 10-9), NCOA2 (P = 1.6 × 10-8), and NID2-PTGDR (P = 4.2 × 10-8), and one novel locus associated with TG near WDR11-FGFR2 (P = 2.7 × 10-10). Conditional analyses identified a second signal near CD163-APOBEC1. We then combined results from the East Asian meta-analysis with association results from up to 187,365 European individuals from the Global Lipids Genetics Consortium in a trans-ancestry meta-analysis. This analysis identified (log10Bayes Factor ≥6.1) eight additional novel lipid loci. Among the twelve total loci identified, the index variants at eight loci have demonstrated at least nominal significance with other metabolic traits in prior studies, and two loci exhibited coincident eQTLs (P < 1 × 10-5) in subcutaneous adipose tissue for BPTF and PDGFC. Taken together, these analyses identified multiple novel lipid loci, providing new potential therapeutic targets

Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P &lt; 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.</p

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution. A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Peer reviewe

Discordant Risk: Overweight and Cardiometabolic Risk in Chinese Adults

Recent US work identifies “metabolically healthy overweight” and “metabolically at risk normal weight” individuals. Less is known for modernizing countries with recent increased obesity. Fasting blood samples, anthropometry and blood pressure from 8,233 adults aged 18–98 in the 2009 nationwide China Health and Nutrition Survey, were used to determine prevalence of overweight (Asian cut point, BMI≥23 kg/m2) and five risk factors [pre-diabetes/diabetes (HbA1c≥5.7%) inflammation (hsCRP ≥3 mg/L), pre-hypertension/hypertension (SBP/DBP≥130/85 mmHg), high triglycerides (≥150 mg/dL), low high-density lipoprotein cholesterol (70 years: 73%). Abdominal obesity was highly predictive of metabolic risk, irrespective of overweight (e.g., “metabolically at risk overweight” relative to “metabolically healthy normal weight” [men: Relative Risk Ratio (RRR) =39.06; 95% Confidence Interval (CI): 23.47, 65.00; women: RRR=22.26; 95% CI: 17.49, 28.33]). To conclude, a large proportion of Chinese adults have metabolic abnormalities. High hypertension risk with age, irrespective of obesity underlies the low prevalence of metabolically healthy overweight. Screening for cardiometabolic-related outcomes dependent upon overweight will likely miss a large portion of the Chinese at-risk population