Genetic risk for earlier menarche also influences peripubertal body mass index

William Johnson, Audrey C. Choh, Joanne E. Curran, Stefan A. Czerwinski, Claire Bellis, Thomas D. Dyer, John Blangero, Bradford Towne, Ellen W. Demerath

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


It is unclear whether earlier age at menarche is associated with higher body mass index (BMI) because they share a common genetic underpinning. We investigated the impact of single nucleotide polymorphisms (SNPs) influencing menarche timing on peripubertal BMI. For 556 Fels Longitudinal Study children (277 boys/279 girls) born 1928-1992, a genetic risk score (GRS42) was computed as the sum of the number of risk alleles in 42 putative menarche SNPs. Serial BMI Z-scores within ±6.99 years from each individual's age at peak height velocity (Age@PHV) were grouped into seven time points (-6 years, -4 years, -2 years, Age@PHV, +2 years, +4years, and +6 years). Heritability of BMI ranged from 0.53 to 0.85 across the time points. The effect of GRS42 on BMI Z-scores at each time point was modeled using variance components-based procedures. GRS42 had a significant (P < 0.05) effect at every time point; an increase of one risk allele was associated with an increase of 0.03-0.08 BMI Z-scores. A separate score (GRS29) was computed that excluded 13 of the menarche SNPs previously documented to also influence adiposity; significant main effects were observed at Age@PHV+4 and +6 years. This finding supports a causal effect of advanced sexual development on post-Age@PHV BMI. Significant positive GRS42 (or GRS 29)-by-birth year interactions indicate that some genetic influences on BMI have amplified over the 20th century. This gene-by-environment interaction also suggests that children with a genetic predisposition to earlier sexual development might avoid elevated BMI through alteration of their nutritional environment. Am J Phys Anthropol, 2013.

Original languageEnglish (US)
Pages (from-to)10-20
Number of pages11
JournalAmerican Journal of Physical Anthropology
Issue number1
StatePublished - Jan 2013


  • body mass index
  • developmental timing
  • genetic variants
  • menarche
  • pleiotropy


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