%0 Journal Article %J Obesity (Silver Spring) %D 2017 %T Exome sequencing reveals novel genetic loci influencing obesity-related traits in Hispanic children. %A Sabo, Aniko %A Mishra, Pamela %A Dugan-Perez, Shannon %A Voruganti, V Saroja %A Kent, Jack W %A Kalra, Divya %A Cole, Shelley A %A Comuzzie, Anthony G %A Muzny, Donna M %A Gibbs, Richard A %A Butte, Nancy F %K Adolescent %K ATPases Associated with Diverse Cellular Activities %K Body Mass Index %K Body Weight %K Child %K Child, Preschool %K Cohort Studies %K Exome %K Genetic Loci %K Genome-Wide Association Study %K Hispanic or Latino %K Humans %K Membrane Proteins %K Pediatric Obesity %K Polymorphism, Single Nucleotide %K Risk Factors %K Sequence Analysis, DNA %K Software %K Waist Circumference %K Young Adult %X

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.

%B Obesity (Silver Spring) %V 25 %P 1270-1276 %8 2017 07 %G eng %N 7 %1 https://www.ncbi.nlm.nih.gov/pubmed/28508493?dopt=Abstract %R 10.1002/oby.21869