Dataset Information

Do genetic risk scores for childhood adiposity operate independent of BMI of their mothers?

ABSTRACT:

Objectives

Genetic predisposition and maternal body mass index (BMI) are risk factors for childhood adiposity, defined by either BMI or overweight. We aimed to investigate whether childhood-specific genetic risk scores (GRSs) for adiposity-related traits are associated with childhood adiposity independent of maternal BMI, or whether the associations are modified by maternal BMI.

Methods

We constructed a weighted 26-SNP child BMI-GRS and a weighted 17-SNP child obesity-GRS in overall 1674 genotyped children within the Danish National Birth Cohort. We applied a case-cohort (N = 1261) and exposure-based cohort (N = 912) sampling design. Using logistic regression models we estimated associations of the GRSs and child overweight at age 7 years and examined if the GRSs influence child adiposity independent of maternal BMI (per standard deviation units).

Results

In the case-cohort design analysis, maternal BMI and the child GRSs were associated with increased odds for childhood overweight [OR for maternal BMI: 2.01 (95% CI: 1.86; 2.17), OR for child BMI-GRS: 1.56 (95% CI: 1.47; 1.66), and OR for child obesity-GRS 1.46 (95% CI: 1.37; 1.54)]. Adjustment for maternal BMI did not change the results, and there were no significant interactions between the GRSs and maternal BMI. However, in the exposure-based cohort design analysis, significant interactions between the child GRSs and maternal BMI on child overweight were observed, suggesting 0.85-0.87-fold attenuation on ORs of child overweight at higher values of maternal BMI and child GRS.

Conclusion

GRSs for childhood adiposity are strongly associated with childhood adiposity even when adjusted for maternal BMI, suggesting that the child-specific GRSs and maternal BMI contribute to childhood overweight independent of each other. However, high maternal BMI may attenuate the effects of child GRSs in children.

SUBMITTER: Huang LO

PROVIDER: S-EPMC8380541 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Genome-wide association studies (GWASs) 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 1995 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 body mass index (BMI), adult BMI, liver fat, waist-hip ratio, 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=1746), VAT (N=1742), VAT/SAT ratio (N=1738), liver fat fraction (N=1950) and pericardial fat mass (N=1803) measured by magnetic resonance imaging. RESULTS:Per additional risk allele in the childhood BMI genetic risk score, SAT increased 0.020 s.d. scores (SDS) (95% confidence interval (CI): 0.009 to 0.031, P-value: 3.28 × 10-4) and VAT increased 0.021 SDS (95% CI: 0.009 to 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 to 0.029, P-value: 1.33 × 10-9) and VAT (0.017 SDS increase, CI: 0.010 to 0.025, P-value: 7.00 × 10-6) and negatively with VAT/SAT ratio (-0.012 SDS decrease, CI: -0.019 to -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 to 0.157, P-value: 2.65 × 10-11). Rs7185735 (SAT) was associated with SAT (0.151 SDS, CI: 0.087 to 0.214, P-value: 3.00 × 10-6) and VAT/SAT ratio (-0.126 SDS, CI: -0.186 to -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.