@article {28, title = {Exome sequencing reveals novel genetic loci influencing obesity-related traits in Hispanic children.}, journal = {Obesity (Silver Spring)}, volume = {25}, year = {2017}, month = {2017 07}, pages = {1270-1276}, 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.

}, keywords = {Adolescent, ATPases Associated with Diverse Cellular Activities, Body Mass Index, Body Weight, Child, Child, Preschool, Cohort Studies, Exome, Genetic Loci, Genome-Wide Association Study, Hispanic or Latino, Humans, Membrane Proteins, Pediatric Obesity, Polymorphism, Single Nucleotide, Risk Factors, Sequence Analysis, DNA, Software, Waist Circumference, Young Adult}, issn = {1930-739X}, doi = {10.1002/oby.21869}, author = {Sabo, Aniko and Mishra, Pamela and Dugan-Perez, Shannon and Voruganti, V Saroja and Kent, Jack W and Kalra, Divya and Cole, Shelley A and Comuzzie, Anthony G and Muzny, Donna M and Gibbs, Richard A and Butte, Nancy F} }