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


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.

SUBMITTER: Sabo A 

PROVIDER: S-EPMC5687071 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Publications

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

Sabo Aniko A   Mishra Pamela P   Dugan-Perez Shannon S   Voruganti V Saroja VS   Kent Jack W JW   Kalra Divya D   Cole Shelley A SA   Comuzzie Anthony G AG   Muzny Donna M DM   Gibbs Richard A RA   Butte Nancy F NF  

Obesity (Silver Spring, Md.) 20170516 7


<h4>Objective</h4>To perform whole exome sequencing in 928 Hispanic children and identify variants and genes associated with childhood obesity.<h4>Methods</h4>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  ...[more]

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