Genome-wide copy number variation analysis identifies novel candidate loci associated with pediatric obesity [Omni2.5M Beadchip]. Homo sapiens

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. Overall design: We detected CNVs using iPattern, PennCNV, QuantiSNP, and CNVPartition. We defined a stringent set of variants when each variant was called by at least by two algorithms.