Associations of adult genetic risk scores for adiposity with childhood abdominal, liver and pericardial fat assessed by Magnetic Resonance Imaging

BACKGROUND: Genome-wide association studies (GWAS) identified single nucleotide polymorphisms (SNPs) involved in adult fat distribution. Whether these SNPs also affect abdominal and organ-specific fat accumulation in children is unknown. METHODS: In a population-based prospective cohort study among 1 995 children (median age: 9.8 years, 95% range 9.4;10.8), We tested the associations of six genetic risk scores based on previously identified SNPs for childhood BMI, adult BMI, liver fat, WHR, pericardial fat mass, visceral- and subcutaneous adipose tissue ratio (VAT/SAT ratio), and four individual SAT and VAT associated SNPs, for association with SAT (N=1 746), VAT (N=1 742), VAT/SAT ratio (N=1 738), liver fat fraction (N=1 950), and pericardial fat mass (N=1 803) measured by Magnetic Resonance Imaging. RESULTS: Per additional risk allele in the childhood BMI genetic risk score, SAT increased 0.020 standard deviation scores (SDS), (95% confidence interval (CI) 0.009;0.031, p-value:3.28*10(-4)) and VAT increased 0.021 SDS, 95% CI:0.009;0.032, p-value:4.68*10(-4)). The adult BMI risk score was positively associated with SAT (0.022 SDS increase, CI:0.015;0.029, p-value:1.33*10(-9)), VAT (0.017 SDS increase, CI:0.010;0.025, p-value:7.00*10(-6)), and negatively with VAT/SAT ratio (-0.012 SDS decrease, CI:-0.019;-0.006, p-value:2.88*10(-4)). The liver fat risk score was associated with liver fat fraction (0.121 SDS, CI:0.086;0.157, p-value:2.65*10(-11)). Rs7185735 (SAT), was associated with SAT (0.151 SDS, CI:0.087;0.214, p-value:3.00*10(-6)) and VAT/SAT ratio (-0.126 SDS, CI:-0.186;-0.065, p-value:4.70*10(-5)). After stratification by sex the associations of the adult BMI risk score with SAT and VAT and of the liver fat risk score with liver fat fraction remained in both sexes. Associations of the childhood BMI risk score with SAT, and the adult BMI risk score with VAT/SAT ratio were present among boys only, whereas the association of the pericardial fat risk score with pericardial fat was present among girls only. CONCLUSION: Genetic variants associated with BMI, body fat distribution, liver and pericardial fat already affect body fat distribution in childhood.