학술논문

Genetic risk for earlier menarche also influences peripubertal body mass index.
Document Type
Article
Source
American Journal of Physical Anthropology. Jan2013, Vol. 150 Issue 1, p10-20. 11p.
Subject
*MENARCHE
*BODY mass index
*PUBERTY
*GENOTYPE-environment interaction
*SINGLE nucleotide polymorphisms
*LONGITUDINAL method
*PHYSIOLOGY
Language
ISSN
0002-9483
Abstract
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 GRS29)-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. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]