Genome-wide copy number variation analysis identifies novel candidate loci associated with pediatric obesity

Eur J Hum Genet. 2018 Nov;26(11):1588-1596. doi: 10.1038/s41431-018-0189-0. Epub 2018 Jul 5.

Abstract

Obesity is a multifactorial condition that is highly heritable. There have been ~60 susceptibility loci identified, but they only account for a fraction of cases. As copy number variations (CNVs) have been implicated in the etiology of a multitude of human disorders including obesity, here, we investigated the contribution of rare (<1% population frequency) CNVs in pediatric cases of obesity. We genotyped 67 such individuals, including 22 with co-morbid developmental delay and prioritized rare CNVs at known obesity-associated loci, as well as, those impacting genes involved in energy homeostasis or related processes. We identified clinically relevant or potentially clinically relevant CNVs in 15% (10/67) of individuals. Of these, 4% (3/67) had 16p11.2 microdeletions encompassing the known obesity risk gene SH2B1. Notably, we identified two unrelated probands harboring different 6p22.2 microduplications encompassing SCGN, a potential novel candidate gene for obesity. Further, we identified other biologically relevant candidate genes for pediatric obesity including ARID5B, GPR39, PTPRN2, and HNF4G. We found previously reported candidate loci for obesity, and new ones, suggesting CNV analysis may assist in the diagnosis of pediatric obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adolescent
  • Child, Preschool
  • DNA Copy Number Variations*
  • DNA-Binding Proteins / genetics
  • Female
  • Genetic Loci*
  • Genome-Wide Association Study
  • Hepatocyte Nuclear Factor 4 / genetics
  • Humans
  • Male
  • Obesity / genetics*
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8 / genetics
  • Receptors, G-Protein-Coupled / genetics
  • Secretagogins / genetics
  • Transcription Factors / genetics

Substances

  • ARID5B protein, human
  • Adaptor Proteins, Signal Transducing
  • DNA-Binding Proteins
  • GPR39 protein, human
  • HNF4G protein, human
  • Hepatocyte Nuclear Factor 4
  • Receptors, G-Protein-Coupled
  • SCGN protein, human
  • SH2B1 protein, human
  • Secretagogins
  • Transcription Factors
  • PTPRN2 protein, human
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8

Grants and funding