Obesity-susceptibility loci and the tails of the pediatric BMI distribution

Area of Science:

• Genetics
• Pediatrics
• Obesity Research

Background:

• Genetic susceptibility loci for adult obesity have been identified.
• The uniform association of these loci with childhood Body Mass Index (BMI) across the entire BMI distribution is not well understood.

Purpose of the Study:

• To investigate whether previously identified adult obesity susceptibility loci are associated uniformly with childhood BMI.
• To examine the association of these loci across the full spectrum of childhood BMI distribution.

Main Methods:

• A cohort of 7,225 children was recruited from the Children's Hospital of Philadelphia.
• Quantile regression was used to assess the association between eight specific obesity susceptibility loci (FTO, MC4R, TMEM18, BDNF, TNNI3K, NRXN3, SEC16B, GNPDA2) and BMI z-scores.
• A genotype risk score was calculated as the sum of risk alleles carried at these eight loci.

Main Results:

• Each increase in the genotype risk score was significantly associated with an increased BMI z-score across various percentiles.
• The association between genotype risk score and BMI z-score was stronger at higher percentiles (e.g., 75th, 85th) compared to lower percentiles (e.g., 5th, 15th).
• A significant overall increase in mean BMI z-score was observed with each increment in the genotype risk score (P = 4.27 × 10(-20)).

Conclusions:

• Genetic variants associated with obesity risk demonstrate a stronger association with higher BMI z-scores in children.
• These findings indicate that obesity risk alleles contribute more substantially to the upper tail of the childhood BMI distribution.
• The study highlights the differential impact of genetic predisposition on childhood obesity severity.