Exome sequencing reveals novel genetic loci influencing obesity-related traits in Hispanic children

Aniko Sabo, Pamela Mishra, Shannon Dugan-Perez, V. Saroja Voruganti, Jack W. Kent, Divya Kalra, Shelley A. Cole, Anthony G. Comuzzie, Donna M. Muzny, Richard A. Gibbs, Nancy F. Butte

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Objective: To perform whole exome sequencing in 928 Hispanic children and identify variants and genes associated with childhood obesity. Methods: Single-nucleotide variants (SNVs) were identified from Illumina whole exome sequencing data using integrated read mapping, variant calling, and an annotation pipeline (Mercury). Association analyses of 74 obesity-related traits and exonic variants were performed using SeqMeta software. Rare autosomal variants were analyzed using gene-based association analyses, and common autosomal variants were analyzed at the SNV level. Results: (1) Rare exonic variants in 10 genes and 16 common SNVs in 11 genes that were associated with obesity traits in a cohort of Hispanic children were identified, (2) novel rare variants in peroxisome biogenesis factor 1 (PEX1) associated with several obesity traits (weight, weight z score, BMI, BMI z score, waist circumference, fat mass, trunk fat mass) were discovered, and (3) previously reported SNVs associated with childhood obesity were replicated. Conclusions: Convergence of whole exome sequencing, a family-based design, and extensive phenotyping discovered novel rare and common variants associated with childhood obesity. Linking PEX1 to obesity phenotypes poses a novel mechanism of peroxisomal biogenesis and metabolism underlying the development of childhood obesity.

Original languageEnglish (US)
Pages (from-to)1270-1276
Number of pages7
JournalObesity
Volume25
Issue number7
DOIs
StatePublished - Jul 1 2017
Externally publishedYes

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Nutrition and Dietetics

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    Sabo, A., Mishra, P., Dugan-Perez, S., Voruganti, V. S., Kent, J. W., Kalra, D., Cole, S. A., Comuzzie, A. G., Muzny, D. M., Gibbs, R. A., & Butte, N. F. (2017). Exome sequencing reveals novel genetic loci influencing obesity-related traits in Hispanic children. Obesity, 25(7), 1270-1276. https://doi.org/10.1002/oby.21869