Cluster Analysis Reveals Important Determinants of Cardiometabolic Risk Patterns in Filipino Women

With modernization, the Philippines has experienced increasing rates of obesity and related cardiometabolic diseases. Studying how risk factors cluster in individuals may offer insight into cardiometabolic disease etiology. We used cluster analysis to group women who share the following cardiometabolic biomarkers: fasting triglycerides, HDL-C and LDL-C, C-reactive protein, systolic and diastolic blood pressure, homeostasis model assessment of insulin resistance, and fasting glucose. Participants included 1,768 women (36–69 y) in the Cebu Longitudinal Health and Nutrition Survey. We identified 5 distinct clusters characterized by: (1) low levels of all risk factors (except HDL-C and LDL-C) or “healthy”, (2) low HDL-C in the absence of other risk factors, (3) elevated blood pressure, (4) insulin resistance, and (5) high C-reactive protein. We identified predictors of cluster membership using multinomial logistic regression. Clusters differed by age, menopausal status, socioeconomic status, saturated fat intake, and combinations of overweight (BMI>23) and high waist circumference (>80cm). In comparison to the healthy cluster, overweight women without high waist circumference were more likely to be in the high CRP cluster (OR 4=2.26, 95% CI=1.24; 4.11), while women with high waist circumference and not overweight were more likely to be in the elevated blood pressure (OR 2.56, 95% CI=1.20; 5.46) or insulin resistant clusters (OR 4.05, 95% CI=1.39; 11.81). In addition, a diet lower in saturated fat uniquely increased the likelihood of membership to the low HDL-C cluster. Cluster analysis identified biologically meaningful groups, predicted by modifiable risk factors; this may have implications for the prevention of cardiometabolic diseases

Clustering and Determinants of Cardiometabolic Risk Factors among Filipino Young Adults

With modernization, cardiometabolic disease risk has increased in low and middle-income countries. To better understand cardiometabolic disease etiology, we evaluated the patterning risk factors in a susceptible young adult population

New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism.

Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism

Early life risk factors of motor, cognitive and language development: a pooled analysis of studies from low/middle-income countries.

OBJECTIVE:To determine the magnitude of relationships of early life factors with child development in low/middle-income countries (LMICs). DESIGN:Meta-analyses of standardised mean differences (SMDs) estimated from published and unpublished data. DATA SOURCES:We searched Medline, bibliographies of key articles and reviews, and grey literature to identify studies from LMICs that collected data on early life exposures and child development. The most recent search was done on 4 November 2014. We then invited the first authors of the publications and investigators of unpublished studies to participate in the study. ELIGIBILITY CRITERIA FOR SELECTING STUDIES:Studies that assessed at least one domain of child development in at least 100 children under 7 years of age and collected at least one early life factor of interest were included in the study. ANALYSES:Linear regression models were used to assess SMDs in child development by parental and child factors within each study. We then produced pooled estimates across studies using random effects meta-analyses. RESULTS:We retrieved data from 21 studies including 20 882 children across 13 LMICs, to assess the associations of exposure to 14 major risk factors with child development. Children of mothers with secondary schooling had 0.14 SD (95% CI 0.05 to 0.25) higher cognitive scores compared with children whose mothers had primary education. Preterm birth was associated with 0.14 SD (-0.24 to -0.05) and 0.23 SD (-0.42 to -0.03) reductions in cognitive and motor scores, respectively. Maternal short stature, anaemia in infancy and lack of access to clean water and sanitation had significant negative associations with cognitive and motor development with effects ranging from -0.18 to -0.10 SDs. CONCLUSIONS:Differential parental, environmental and nutritional factors contribute to disparities in child development across LMICs. Targeting these factors from prepregnancy through childhood may improve health and development of children

New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism

Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood(1). Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits(2). In an expanded genome-wide association metaanalysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism

Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma.

Concentrations of liver enzymes in plasma are widely used as indicators of liver disease. We carried out a genome-wide association study in 61,089 individuals, identifying 42 loci associated with concentrations of liver enzymes in plasma, of which 32 are new associations (P = 10(-8) to P = 10(-190)). We used functional genomic approaches including metabonomic profiling and gene expression analyses to identify probable candidate genes at these regions. We identified 69 candidate genes, including genes involved in biliary transport (ATP8B1 and ABCB11), glucose, carbohydrate and lipid metabolism (FADS1, FADS2, GCKR, JMJD1C, HNF1A, MLXIPL, PNPLA3, PPP1R3B, SLC2A2 and TRIB1), glycoprotein biosynthesis and cell surface glycobiology (ABO, ASGR1, FUT2, GPLD1 and ST3GAL4), inflammation and immunity (CD276, CDH6, GCKR, HNF1A, HPR, ITGA1, RORA and STAT4) and glutathione metabolism (GSTT1, GSTT2 and GGT), as well as several genes of uncertain or unknown function (including ABHD12, EFHD1, EFNA1, EPHA2, MICAL3 and ZNF827). Our results provide new insight into genetic mechanisms and pathways influencing markers of liver function