Genome-wide copy number variation analysis identifies novel candidate loci associated with pediatric obesity.
Thanuja SelvanayagamSusan WalkerMatthew J GazzelloneBarbara KellamCheryl CytrynbaumDimitri J StavropoulosPing LiCatherine S BirkenJill HamiltonRosanna WeksbergStephen W SchererPublished in: European journal of human genetics : EJHG (2018)
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.
Keyphrases
- genome wide
- copy number
- insulin resistance
- metabolic syndrome
- weight loss
- high fat diet induced
- type diabetes
- weight gain
- dna methylation
- mitochondrial dna
- bariatric surgery
- adipose tissue
- gene expression
- risk assessment
- endothelial cells
- high resolution
- inflammatory response
- cord blood
- atomic force microscopy
- high speed