Novel signals and polygenic score for height are associated with pubertal growth traits in Southwestern American Indians.

Most genetic variants associated with adult height have been identified through large genome-wide association studies (GWASs) in European-ancestry cohorts. However, it is unclear how these variants influence linear growth during adolescence. This study uses anthropometric and genotypic data from a longitudinal study conducted in an American Indian community in Arizona between 1965-2007. Growth parameters (i.e. height, velocity, and timing of growth spurt) were derived from the Preece-Baines growth model, a parametric growth curve fitted to longitudinal height data, in 787 participants with height measurements spanning the whole period of growth. Heritability estimates suggested that genetic factors could explain 25% to 71% of the variance of pubertal growth traits. We performed a GWAS of growth parameters, testing their associations with 5 077 595 imputed or directly genotyped variants. Six variants associated with height at peak velocity (P < 5 × 10-8, adjusted for sex, birth year and principal components). Implicated genes include NUDT3, previously associated with adult height, and PACSIN1. Two novel variants associated with duration of growth spurt (P < 5 × 10-8) in LOC105375344, an uncharacterized gene with unknown function. We finally examined the association of growth parameters with a polygenic score for height derived from 9557 single nucleotide polymorphisms (SNPs) identified in the GIANT meta-analysis for which genotypic data were available for the American Indian study population. Height polygenic score was correlated with the magnitude and velocity of height growth that occurred before and at the peak of the adolescent growth spurt, indicating overlapping genetic architecture, with no influence on the timing of adolescent growth.

A Mixed-Longitudinal Study of Height Velocity of Greek Schoolchildren and the Milestones of the Adolescent Growth Spurt.

Height velocity (HV) growth charts constructed from longitudinal studies are scarce as they have inherent difficulties, e.g., time, and costs. These difficulties can be partly overcome by a mixed-longitudinal study that covers the entire age range within 3-6 years. To construct HV charts of Greek children and to estimate the milestones of the adolescent growth spurt (AGS), i.e., the onset of AGS (take-off), peak HV, and total pubertal growth (TPG), we performed a mixed longitudinal study in 1514 Greek schoolchildren (6-18 years) with height measurements every 6 months during three schoolyears. We constructed HV charts for boys and girls. Take-off occurs earlier in girls, and, in both sexes, it precedes by 1-1.5 years the appearance of physical signs of puberty. PHV in boys occurs at 12.61 years and in girls at 10.93 years. At take-off, boys are 5 cm taller than girls and TPG for boys is 35.8 cm and for girls 27.3 cm. We constructed HV charts plotted by age, irrespective of pubertal status, and presented data on the milestones of AGS. Furthermore, we suggest that the gradual increase in IGF-1 and E2 that occurs after 5 to 6 years of age triggers the onset of AGS, which precedes physical signs of puberty.