Adult obesity susceptibility variants are associated with greater childhood weight gain and a faster tempo of growth: the 1946 British Birth Cohort Study(1)(2)(3)

Background: Longitudinal growth associations with genetic variants identified for adult BMI may provide insights into the timing of obesity susceptibility. Objective: The objective was to explore associations of known BMI loci with measures of body size from birth to adulthood. Design: A total of 2537 individuals from a longitudinal British birth cohort were genotyped for 11 genetic variants robustly associated with adult BMI (in/near FTO, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, ETV5, SEC16B, SH2B1, and MTCH2). We derived an obesity-risk-allele score, comprising the sum of BMI-increasing alleles in each individual, and examined this for an association with birth weight and repeated measures of weight, height, and BMI SD scores (SDS) at 11 time points between ages 2 and 53 y. Results: The obesity-risk-allele score showed borderline significant association with birth weight (0.019 SDS/allele; P = 0.05) and was more clearly associated with higher weight and BMI at all time points between ages 2 and 53 y; the strongest associations with weight occurred at ages 11 and 20 y (both 0.056 SDS/allele). In longitudinal analyses, the score was positively associated with weight gain only between birth and 11 y (0.003 SDS/allele per year; 95% CI: 0.001, 0.004; P = 0.001). The risk-allele score was associated with taller height at 7 y (0.031 SDS/allele; P = 0.002) and greater height gains between 2 and 7 y (0.007 SDS/allele per year; P < 0.001), but not with adult height (P = 0.5). Conclusions: The combined effect of adult obesity susceptibility variants on weight gain was confined to childhood. These variants conferred a faster tempo of height growth that was evident before the pubertal years.