Researchers from Children’s Hospital of Philadelphia (CHOP) and the University of Pennsylvania identified a genetic variant linked to childhood obesity. This variant, characterized by a single alteration in the genetic code, significantly influences a child’s susceptibility to being overweight or obese.
“chr12q13 locus” linked to obesity
The study published in Cell Genomics examined a specific area on chromosome 12 previously identified in genome-wide association studies (GWAS) as correlated with childhood obesity risk. GWAS analyze large populations’ genomes to identify genetic markers linked to traits or diseases.
Researchers have identified a significant genetic locus, termed the “chr12q13 locus,” in childhood obesity studies. Despite its importance, the specific genes involved and their impact on body weight were unclear. Through advanced genomic methods, scientists pinpointed a single genetic variant, rs7132908, characterized by a “G” to “A” alteration in DNA. This variant resides in a regulatory region affecting nearby gene activity.
FAIM2 is a crucial gene in neuron development and survival, particularly in the hypothalamus, the brain’s control center for appetite and body weight regulation.
Dr. Sheridan H. Littleton, a postdoctoral research associate at CHOP’s Center for Spatial and Functional Genomics team, highlights the identification of a causal variant linked to childhood obesity, which holds promise for potential therapies tailored to address this condition.
Obesity risk variant rs7132908 dampens FAIM2 expression
Researchers discovered that the obesity risk variant rs7132908 reduces FAIM2 expression in hypothalamic neurons, dampening the activity of this crucial gene during brain development. They employed CRISPR gene editing on stem cell-grown neurons to create two groups: one with the non-risk “G” variant and the other with the obesity-risk “A” variant.
Results showed that neurons with the “A” variant had lower FAIM2 levels and were significantly less likely to mature into specialized neurons that regulate appetite, with only 11% compared to 61% in the “G” variant neurons.
Researchers suggest that reduced FAIM2 levels during a crucial period of hypothalamic development may result in an imbalance between appetite-stimulating and appetite-suppressing neurons in children. This imbalance could potentially lead to overeating and weight gain in the long term.
