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

Purpose: Obesity is known to be 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 CNVs (<0.1% population frequency) in pediatric cases of obesity. Methods: We genotyped 67 pediatric patients presenting with obesity, including 22 with co-morbid developmental delay and prioritized rare CNVs at known associated loci, as well as, those impacting genes involved in energy homeostasis or related processes. Results: 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. Conclusion: We found previously reported candidate loci for obesity, and new ones, suggesting CNV analysis may assist in the diagnosis of pediatric obesity. DNA was genotyped using the Affymetrix CytoScan HD array at TCAG using the manufacturer's protocol We identified CNVs using Affymetrix Chromosome Analysis Suite, iPattern, Nexus, and Partek. CNVs were classified as stringent when called by at least two algorithms.