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

Obesity
Aniko SaboNancy F Butte

Abstract

To perform whole exome sequencing in 928 Hispanic children and identify variants and genes associated with childhood obesity. 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. (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. 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 bi...Continue Reading

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Citations

Jan 23, 2019·Diabetes, Obesity & Metabolism·Dharambir K SangheraPiers R Blackett
Aug 23, 2020·International Journal of Molecular Sciences·Michal CohenDov Tiosano
Mar 21, 2021·NPJ Genomic Medicine·Savannah MwesigwaNeil A Hanchard
Jun 16, 2021·American Journal of Human Genetics·He LiRichard A Gibbs

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Methods Mentioned

BETA
exome sequencing
Human Genome Sequencing
PCA

Software Mentioned

Polyphen2
GIANT
Sequential Oligogenic Linkage Analysis Routines ( SOLAR )
kinship2
WST
Atlas
Primus
GENESIS
VIVA
BWA

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