Associations between menarche-related genetic variants and pubertal growth in male and female adolescents

Previous studies have identified novel genetic variants associated with age at menarche in females of European descent. The pubertal growth effects of these variants have not been carefully evaluated in non-European descent groups. We aimed to examine the effects of 31 newly identified menarche-related single-nucleotide polymorphisms (SNPs) on growth outcomes in African-American (AA) and European-American (EA) children in a prospective cohort.

We analyzed longitudinal data collected from 263 AAs and 338 EAs enrolled between ages 5 and 17 years; the subjects were followed semiannually for an average of 6 years. The associations between the SNPs and growth-related outcomes, including weight, height, and body mass index (BMI), were examined using mixed-effect models.

Longitudinal analyses revealed that 4 (near or in genes VGLL3, PEX2, CA10, and SKOR2) of the 14 menarche-only-related SNPs were associated with changes in weight and BMI in EA and AA (p ≤ .0032), but none of them was associated with changes in height. Of the eight menarche-timing and BMI-related SNPs, none was associated with changes in height, but three (in or near genes NEGR1, ETV5, and FTO) were associated with more rapid increases in weight and/or BMI in EA (p ≤ .0059). Among the nine menarche-timing and height-related SNPs, four (in or near genes ZBTB38, LOC728666, TBX2, and CABLES) were associated with changes in weight or height in EA and AA (p ≤ .0042).

Genetic variants related to age at menarche were found to be associated with various growth parameters in healthy adolescents. The identified associations were often race and sex specific.