title: 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.
authors.affiliation: Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, USA.
authors.forename: William
authors.initials: W
authors.lastname: Johnson
authors.forename: Audrey C
authors.initials: AC
authors.lastname: Choh
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Curran
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Czerwinski
authors.forename: Claire
authors.initials: C
authors.lastname: Bellis
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Dyer
authors.forename: John
authors.initials: J
authors.lastname: Blangero
authors.forename: Bradford
authors.initials: B
authors.lastname: Towne
authors.forename: Ellen W
authors.initials: EW
authors.lastname: Demerath
mesh_terms: D000293:Adolescent; D041923:Adolescent Development / Q000502:physiology*; D000885:Anthropology, Physical; D001827:Body Height; D015992:Body Mass Index; D002648:Child; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008572:Menarche / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011627:Puberty / Q000235:genetics* / Q000502:physiology; D012044:Regression Analysis