Parental and child genetic contributions to obesity traits in early life based on 83 loci validated in adults: the FAMILY study.

Abstract

The genetic influence on child obesity has not been fully elucidated. This study investigated the parental and child contributions of 83 adult body mass index (BMI)-associated single-nucleotide polymorphisms (SNPs) to obesity-related traits in children from birth to 5years old. A total of 1402 individuals were genotyped for 83 SNPs. An unweighted genetic risk score (GRS) was generated by the sum of BMI-increasing alleles. Repeated weight and length/height were measured at birth, 1, 2, 3 and 5years of age, and age-specific and sex-specific weight and BMI Z-scores were computed. The GRS was significantly associated with birthweight Z-score (P=0.03). It was also associated with weight/BMI Z-score gain between birth and 5years old (P=0.02 and 6.77×10-3 , respectively). In longitudinal analyses, the GRS was associated with weight and BMI Z-score from birth to 5years (P=5.91×10-3 and 5.08×10-3 , respectively). The maternal effects of rs3736485 in DMXL2 on weight and BMI variation from birth to 5years were significantly greater compared with the paternal effects by Z test (P=1.53×10-6 and 3.75×10-5 , respectively). SNPs contributing to adult BMI exert their effect at birth and in early childhood. Parent-of-origin effects may occur in a limited subset of obesity predisposing SNPs.