Transcriptome-wide association study identifies multiple genes associated with childhood body mass index.

Abstract

Childhood obesity is one of the most common and costly nutritional problems with high heritability. The genetic mechanism of childhood obesity remains unclear. Here, we conducted a transcriptome-wide association study (TWAS) to identify novel genes for childhood obesity. By integrating the GWAS summary of childhood body mass index (BMI), we conducted TWAS analyses with pre-computed gene expression weights in 39 obesity priority tissues. The GWAS summary statistics of childhood BMI were derived from the early growth genetics consortium with 35,668 children from 20 studies. We identified 15 candidate genes for childhood BMI after Bonferroni corrections. The most significant gene, ADCY3, was identified in 13 tissues, including adipose, brain, and blood. Interestingly, eight genes were only identified in the specific tissue, such as FAIM2 in the brain (P = 2.04 × 10^-7) and fat mass and obesity-associated gene (FTO) in the muscle (P = 1.93 × 10^-8). Compared with the TWAS results of adult BMI, we found that one gene TUBA1B with predominant influence only on childhood BMI in the muscle (P = 1.12 × 10^-7). We evaluated the candidate genes by querying public databases and identified 12 genes functionally related to obesity phenotypes, including nine differentially expressed genes during the differentiation of human preadipocyte cells. The remaining genes (FAM150B, KNOP1, and LMBR1L) were regarded as novel candidate genes for childhood BMI. Our study identified multiple candidate genes for childhood BMI, providing novel clues for understanding the genetic mechanism of childhood obesity.