TY - JOUR
T1 - Modeling metabolic syndrome through structural equations of metabolic traits, comorbid diseases, and GWAS variants
AU - Karns, Rebekah
AU - Succop, Paul
AU - Zhang, Ge
AU - Sun, Guangyun
AU - Indugula, Subba R.
AU - Havas-Augustin, Dubravka
AU - Novokmet, Natalija
AU - Durakovic, Zijad
AU - Milanovic, Sanja Music
AU - Missoni, Sasa
AU - Vuletic, Silvije
AU - Chakraborty, Ranajit
AU - Rudan, Pavao
AU - Deka, Ranjan
PY - 2013/12
Y1 - 2013/12
N2 - Objective 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). Design and Methods 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. Results 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. Conclusions Although MetS was associated with obesity, dyslipidemia, glucose control, hypertension, and hyperuricemia, limited ability of MetS to indicate metabolic disease risk is suggested.
AB - Objective 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). Design and Methods 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. Results 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. Conclusions Although MetS was associated with obesity, dyslipidemia, glucose control, hypertension, and hyperuricemia, limited ability of MetS to indicate metabolic disease risk is suggested.
UR - http://www.scopus.com/inward/record.url?scp=84889648995&partnerID=8YFLogxK
U2 - 10.1002/oby.20445
DO - 10.1002/oby.20445
M3 - Article
C2 - 23512735
AN - SCOPUS:84889648995
VL - 21
SP - E745-E754
JO - Obesity
JF - Obesity
SN - 1930-7381
IS - 12
ER -