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Pediatrics

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

International Journal of Obesity volume 45, pages 1105–1113 (2021)Cite this article

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

Our study identified multiple candidate genes for childhood BMI, providing novel clues for understanding the genetic mechanism of childhood obesity.

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Fig. 1: TWAS results for childhood BMI.
Fig. 2: Scatter plot of common gene ontology terms shared by TWAS and mRNA expression profiling of human Simpson–Golabi–Behmel Syndrome (SGBS) preadipocyte cells.

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Acknowledgements

This study is supported by the National Natural Science Foundation of China (31871264 and 32070588); Shaanxi Provincial Key Research and Development Project (2019ZDLSF01-09); the Innovative Talent Promotion Plan of Shaanxi Province for Young Sci-Tech New Star (2018KJXX-010); and the Fundamental Research Funds for the Central Universities. This study is also supported by the High-Performance Computing Platform of Xi’an Jiaotong University.

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  1. These authors contributed equally: Shi Yao, Hao Wu

Authors and Affiliations

  1. Key Laboratory of Biomedical Information Engineering of Ministry of Education, Biomedical Informatics & Genomics Center, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, Shaanxi, PR China

    Shi Yao, Hao Wu, Jing-Miao Ding, Zhuo-Xin Wang, Tahir Ullah, Shan-Shan Dong, Hao Chen & Yan Guo

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Yao, S., Wu, H., Ding, JM. et al. Transcriptome-wide association study identifies multiple genes associated with childhood body mass index. Int J Obes 45, 1105–1113 (2021). https://doi.org/10.1038/s41366-021-00780-y

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