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

Area of Science:

• Genetics
• Pediatrics
• Nutritional Science

Background:

• Childhood obesity is a prevalent and costly nutritional issue with significant heritability.
• The precise genetic underpinnings of childhood obesity are not fully understood.
• Identifying genetic factors is crucial for understanding and addressing this public health challenge.

Purpose of the Study:

• To identify novel genes associated with childhood obesity through a transcriptome-wide association study (TWAS).
• To explore the genetic architecture of childhood body mass index (BMI).

Main Methods:

• Conducted TWAS by integrating genome-wide association study (GWAS) summary statistics for childhood BMI with gene expression data from 39 key tissues.
• Utilized GWAS data from the Early Growth Genetics Consortium, encompassing 35,668 children across 20 studies.

Main Results:

• Identified 15 candidate genes for childhood BMI after applying Bonferroni correction.
• ADCY3 was the most significant gene, detected in 13 tissues including adipose, brain, and blood.
• Discovered tissue-specific genes, such as FAIM2 in the brain and the fat mass and obesity-associated gene (FTO) in muscle, and identified TUBA1B as uniquely influencing childhood BMI in muscle.

Conclusions:

• The study successfully identified multiple candidate genes contributing to childhood BMI.
• These findings provide novel genetic insights into the mechanisms underlying childhood obesity.
• Three genes (FAM150B, KNOP1, and LMBR1L) were highlighted as potentially novel genetic factors for childhood BMI.