TY - JOUR
T1 - Exome sequencing reveals novel genetic loci influencing obesity-related traits in Hispanic children
AU - Sabo, Aniko
AU - Mishra, Pamela
AU - Dugan-Perez, Shannon
AU - Voruganti, V. Saroja
AU - Kent, Jack W.
AU - Kalra, Divya
AU - Cole, Shelley A.
AU - Comuzzie, Anthony G.
AU - Muzny, Donna M.
AU - Gibbs, Richard A.
AU - Butte, Nancy F.
N1 - Publisher Copyright:
© 2017 The Obesity Society
PY - 2017/7
Y1 - 2017/7
N2 - 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.
AB - 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.
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U2 - 10.1002/oby.21869
DO - 10.1002/oby.21869
M3 - Article
C2 - 28508493
AN - SCOPUS:85019892055
VL - 25
SP - 1270
EP - 1276
JO - Obesity
JF - Obesity
SN - 1930-7381
IS - 7
ER -