Title: Modeling metabolic syndrome through structural equations of metabolic traits, comorbid diseases, and GWAS variants.
Authors: Karns, Rebekah; Succop, Paul; Zhang, Ge; Sun, Guangyun; Indugula, Subba R; Havas-Augustin, Dubravka; Novokmet, Natalija; Durakovic, Zijad; Milanovic, Sanja Music; Missoni, Sasa; Vuletic, Silvije; Chakraborty, Ranajit; Rudan, Pavao; Deka, Ranjan
Published In Obesity (Silver Spring), (2013 Dec)
Abstract: To provide a quantitative map of relationships between metabolic traits, genome-wide association studies (GWAS) variants, metabolic syndrome (MetS), and metabolic diseases through factor analysis and structural equation modeling (SEM).Cross-sectional data were collected on 1,300 individuals from an eastern Adriatic Croatian island, including 14 anthropometric and biochemical traits, and diagnoses of type 2 diabetes, coronary heart disease, gout, kidney disease, and stroke. MetS was defined based on Adult Treatment Panel III criteria. Forty widely replicated GWAS variants were genotyped. Correlated quantitative traits were reduced through factor analysis; relationships between factors, genetic variants, MetS, and metabolic diseases were determined through SEM.MetS was associated with obesity (P < 0.0001), dyslipidemia (P < 0.0001), glycated hemoglobin (HbA1c; P = 0.0013), hypertension (P < 0.0001), and hyperuricemia (P < 0.0001). Of metabolic diseases, MetS was associated with gout (P = 0.024), coronary heart disease was associated with HbA1c (P < 0.0001), and type 2 diabetes was associated with HbA1c (P < 0.0001) and obesity (P = 0.008). Eleven GWAS variants predicted metabolic variables, MetS, and metabolic diseases. Notably, rs7100623 in HHEX/IDE was associated with HbA1c (β = 0.03; P < 0.0001) and type 2 diabetes (β = 0.326; P = 0.0002), underscoring substantial impact on glucose control.Although MetS was associated with obesity, dyslipidemia, glucose control, hypertension, and hyperuricemia, limited ability of MetS to indicate metabolic disease risk is suggested.
PubMed ID: 23512735
MeSH Terms: Adolescent; Adult; Aged; Aged, 80 and over; Blood Pressure; Comorbidity; Cross-Sectional Studies; Dyslipidemias/epidemiology; Female; Genome-Wide Association Study*; Genotype; Glycated Hemoglobin A/metabolism; Humans; Hypertension/epidemiology; Hyperuricemia/epidemiology; Male; Metabolic Syndrome/epidemiology*; Metabolic Syndrome/genetics*; Middle Aged; Multivariate Analysis; Obesity/epidemiology; Phenotype; Regression Analysis; Risk Factors; Young Adult