TY - JOUR
T1 - Genetic epidemiology of cardiometabolic risk factors and their clustering patterns in Mexican American children and adolescents
T2 - The SAFARI Study
AU - Fowler, Sharon P.
AU - Puppala, Sobha
AU - Arya, Rector
AU - Chittoor, Geetha
AU - Farook, Vidya S.
AU - Schneider, Jennifer
AU - Resendez, Roy G.
AU - Upadhayay, Ram Prasad
AU - Vandeberg, Jane
AU - Hunt, Kelly J.
AU - Bradshaw, Benjamin
AU - Cersosimo, Eugenio
AU - Vandeberg, John L.
AU - Almasy, Laura
AU - Curran, Joanne E.
AU - Comuzzie, Anthony G.
AU - Lehman, Donna M.
AU - Jenkinson, Christopher P.
AU - Lynch, Jane L.
AU - Defronzo, Ralph A.
AU - Blangero, John
AU - Hale, Daniel E.
AU - Duggirala, Ravindranath
PY - 2013/9/1
Y1 - 2013/9/1
N2 - Pediatric metabolic syndrome (MS) and its cardiometabolic components (MSCs) have become increasingly prevalent, yet little is known about the genetics underlying MS risk in children. We examined the prevalence and genetics of MS-related traits among 670 non-diabetic Mexican American (MA) children and adolescents, aged 6-17 years (49 % female), who were participants in the San Antonio Family Assessment of Metabolic Risk Indicators in Youth study. These children are offspring or biological relatives of adult participants from three well-established Mexican American family studies in San Antonio, TX, at increased risk of type 2 diabetes. MS was defined as ≥3 abnormalities among 6 MSC measures: waist circumference, systolic and/or diastolic blood pressure, fasting insulin, triglycerides, HDL-cholesterol, and fasting and/or 2-h OGTT glucose. Genetic analyses of MS, number of MSCs (MSC-N), MS factors, and bivariate MS traits were performed. Overweight/obesity (53 %), pre-diabetes (13 %), acanthosis nigricans (33 %), and MS (19 %) were strikingly prevalent, as were MS components, including abdominal adiposity (32 %) and low HDL-cholesterol (32 %). Factor analysis of MS traits yielded three constructs: adipo-insulin-lipid, blood pressure, and glucose factors, and their factor scores were highly heritable. MS itself exhibited 68 % heritability. MSC-N showed strong positive genetic correlations with obesity, insulin resistance, inflammation, and acanthosis nigricans, and negative genetic correlation with physical fitness. MS trait pairs exhibited strong genetic and/or environmental correlations. These findings highlight the complex genetic architecture of MS/MSCs in MA children, and underscore the need for early screening and intervention to prevent chronic sequelae in this vulnerable pediatric population.
AB - Pediatric metabolic syndrome (MS) and its cardiometabolic components (MSCs) have become increasingly prevalent, yet little is known about the genetics underlying MS risk in children. We examined the prevalence and genetics of MS-related traits among 670 non-diabetic Mexican American (MA) children and adolescents, aged 6-17 years (49 % female), who were participants in the San Antonio Family Assessment of Metabolic Risk Indicators in Youth study. These children are offspring or biological relatives of adult participants from three well-established Mexican American family studies in San Antonio, TX, at increased risk of type 2 diabetes. MS was defined as ≥3 abnormalities among 6 MSC measures: waist circumference, systolic and/or diastolic blood pressure, fasting insulin, triglycerides, HDL-cholesterol, and fasting and/or 2-h OGTT glucose. Genetic analyses of MS, number of MSCs (MSC-N), MS factors, and bivariate MS traits were performed. Overweight/obesity (53 %), pre-diabetes (13 %), acanthosis nigricans (33 %), and MS (19 %) were strikingly prevalent, as were MS components, including abdominal adiposity (32 %) and low HDL-cholesterol (32 %). Factor analysis of MS traits yielded three constructs: adipo-insulin-lipid, blood pressure, and glucose factors, and their factor scores were highly heritable. MS itself exhibited 68 % heritability. MSC-N showed strong positive genetic correlations with obesity, insulin resistance, inflammation, and acanthosis nigricans, and negative genetic correlation with physical fitness. MS trait pairs exhibited strong genetic and/or environmental correlations. These findings highlight the complex genetic architecture of MS/MSCs in MA children, and underscore the need for early screening and intervention to prevent chronic sequelae in this vulnerable pediatric population.
UR - http://www.scopus.com/inward/record.url?scp=84882596747&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84882596747&partnerID=8YFLogxK
U2 - 10.1007/s00439-013-1315-2
DO - 10.1007/s00439-013-1315-2
M3 - Article
C2 - 23736306
AN - SCOPUS:84882596747
VL - 132
SP - 1059
EP - 1071
JO - Human Genetics
JF - Human Genetics
SN - 0340-6717
IS - 9
ER -