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Genetic epidemiology of cardiometabolic risk factors and their clustering patterns in Mexican American children and adolescents: the SAFARI Study

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Abstract

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.

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Acknowledgments

This study was supported by Grants from the National Institutes of Health (R01 HD049051, HD041111, DK053889, DK042273, K01DK064867, P01 HL045522, DK047482, MH059490, M01-RR-01346, and HD049051-5S1 (ARRA). This work was also supported by a Veterans Administration Epidemiologic grant to R.A.D. In addition, we thank the Fraternal Order of Eagles San Antonio Aerie and Auxiliary for their support. We thank the University Health System and the Texas Diabetes Institute, San Antonio, Texas for extending their excellent facilities to our study. The AT&T Genomics Computing Center supercomputing facilities used for this work were supported in part by a gift from the AT&T Foundation and with support from the National Center for Research Resources Grant Number S10 RR029392. This investigation was conducted in facilities constructed with support from Research Facilities Improvement Program grants C06 RR013556 and C06 RR017515 from the National Center for Research Resources of the National Institutes of Health. We thank Dr. William Rogers, Dr. Rolando Lozano, Dr. Nancy Butte, Anne Adolph, Richard Granato, Margaret Fragoso, David Rupert, Rhonda Lyons, Tanya Prado, Elizabeth Sosa, Bonnie Sanchez, and Nicolas Ballí for their excellent help and assistance. Lastly, and most importantly, we are deeply indebted to the children, teenagers, parents, and extended family members of the SAFARI study, whose great enthusiasm and commitment have made this research possible.

Conflict of interest

The authors have no conflicts of interest to disclose.

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Authors and Affiliations

  1. University of Texas Health Science Center at San Antonio (UTHSCSA), San Antonio, TX, USA

    Sharon P. Fowler, Rector Arya, Eugenio Cersosimo, Donna M. Lehman, Christopher P. Jenkinson, Jane L. Lynch, Ralph A. DeFronzo & Daniel E. Hale

  2. Department of Genetics, Texas Biomedical Research Institute, P.O. Box 760549, San Antonio, TX, 78245-0549, USA

    Sobha Puppala, Geetha Chittoor, Vidya S. Farook, Jennifer Schneider, Roy G. Resendez, Ram Prasad Upadhayay, Jane VandeBerg, John L. VandeBerg, Laura Almasy, Joanne E. Curran, Anthony G. Comuzzie, John Blangero & Ravindranath Duggirala

  3. Medical University of South Carolina, Charleston, SC, USA

    Kelly J. Hunt

  4. School of Public Health, UTHSC-Houston, San Antonio, TX, USA

    Benjamin Bradshaw

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  1. Sharon P. Fowler
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  2. Sobha Puppala
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  3. Rector Arya
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  6. Jennifer Schneider
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  9. Jane VandeBerg
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  12. Eugenio Cersosimo
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  13. John L. VandeBerg
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  17. Donna M. Lehman
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  18. Christopher P. Jenkinson
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  19. Jane L. Lynch
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  20. Ralph A. DeFronzo
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  21. John Blangero
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  22. Daniel E. Hale
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  23. Ravindranath Duggirala
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Correspondence to Ravindranath Duggirala.

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Fowler, S.P., Puppala, S., Arya, R. et al. Genetic epidemiology of cardiometabolic risk factors and their clustering patterns in Mexican American children and adolescents: the SAFARI Study. Hum Genet 132, 1059–1071 (2013). https://doi.org/10.1007/s00439-013-1315-2

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