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 - Funding Information:
We thank the families who participated in the VIVA LA FAMILIA study. The authors wish to acknowledge the contributions of Jennifer E. Below with pedigree reconstruction and Andrew Carroll with SNV identification.
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 -