Polygenic risk, adherence to a healthy lifestyle, and childhood obesity.

BACKGROUND: Both polygenic and unhealthy lifestyle factors contribute to individual-level risk of obesity during childhood. The extent to which increased polygenic risk can be offset by healthy lifestyle is unknown.

OBJECTIVE: To examine whether increased polygenic risk of obesity is modified by a healthy lifestyle during childhood.

METHODS: A total of 997 children (418 boys and 579 girls) who had complete DNA genotyping and body mass index (BMI) were eligible for the study were analyzed from an established prospective puberty cohort. The polygenic risk score (PRS) was computed based on 11 BMI-increasing single nucleotide polymorphisms (SNPs) derived from a published genome-wide association study (GWAS) for child obesity. Seven lifestyle factors were selected to determine a composite healthy lifestyle, such as food responsiveness, slowness in eating, satiety responsiveness, physical activity, screen time, sleep duration, and sugar-sweetened beverages consumption, and which was classified as healthy (<P25 ), intermediate (P25 -P75 ) and unhealthy (>P75 ) lifestyle. Linear and logistic regression analyses were conducted.

RESULTS: Children carrying additional BMI susceptibility alleles increased the BMI by 0.11 kg/m2 , after adjusting gender, age and socio-economic status (SES). A healthy lifestyle was associated with a substantially lower risk of obesity than an unhealthy lifestyle, regardless of the polygenic risk category. Among children at high polygenic risk, a healthy lifestyle was associated with an 85% lower risk of obesity than an unhealthy lifestyle (odds ratio, 0.15; 95% CI, 0.04 to 0.59; p = 0.007).

CONCLUSIONS: Our findings suggest that increased polygenic risk might be largely offset by healthy lifestyle as early as in childhood.