Genetic risk for earlier menarche also influences peripubertal body mass index.

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 (GRS(42)) 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, +4 years, and +6 years). Heritability of BMI ranged from 0.53 to 0.85 across the time points. The effect of GRS(42) on BMI Z-scores at each time point was modeled using variance components-based procedures. GRS(42) 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 (GRS(29)) 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 GRS(42) (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.

journal_name

Am J Phys Anthropol

authors

Johnson W,Choh AC,Curran JE,Czerwinski SA,Bellis C,Dyer TD,Blangero J,Towne B,Demerath EW

doi

10.1002/ajpa.22121

subject

Has Abstract

pub_date

2013-01-01 00:00:00

pages

10-20

issue

1

eissn

0002-9483

issn

1096-8644

journal_volume

150

pub_type

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