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

Obesity (Silver Spring). 2017 Jul;25(7):1270-1276. doi: 10.1002/oby.21869. Epub 2017 May 16.


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.

MeSH terms

  • ATPases Associated with Diverse Cellular Activities / genetics
  • ATPases Associated with Diverse Cellular Activities / metabolism
  • Adolescent
  • Body Mass Index
  • Body Weight
  • Child
  • Child, Preschool
  • Cohort Studies
  • Exome*
  • Genetic Loci*
  • Genome-Wide Association Study
  • Hispanic Americans / genetics*
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Pediatric Obesity / ethnology
  • Pediatric Obesity / genetics*
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Sequence Analysis, DNA*
  • Software
  • Waist Circumference
  • Young Adult


  • Membrane Proteins
  • ATPases Associated with Diverse Cellular Activities
  • PEX1 protein, human