Dataset Information

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.

SUBMITTER: Johnson W

PROVIDER: S-EPMC3539227 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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

Johnson William W Choh Audrey C AC Curran Joanne E JE Czerwinski Stefan A SA Bellis Claire C Dyer Thomas D TD Blangero John J Towne Bradford B Demerath Ellen W EW

American journal of physical anthropology 20130101 1

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 e ...[more]

PMID: 23283660

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Project description:Dietary and physical activity behaviors formed early in life can increase risk for childhood obesity and have continued negative consequences for lifelong health. Previous research has highlighted the importance of both genetic and environmental (e.g., cultural environment or parental lifestyle) contributions to obesity risk, although these studies typically involve genetically-related individuals residing in the same household, where genetic similarity and rearing environment are inextricably linked. Here we utilize a sibling-adoption design to independently estimate genetic and environmental contributions to obesity risk in childhood and describe how these influences might vary as children age. As part of a prospective adoption study, the current investigation used data from biological siblings reared either apart or together, and nonbiological siblings reared together to estimate the contributions of genetics and environment to body mass indices (BMI) in a large cohort of children (N = 711). We used a variance partitioning model to allocate variation in BMI to that which is due to shared genetics, common environment, or unique environment in this cohort during middle childhood and adolescence. We found 63% of the total variance in BMI could be attributed to heritable factors in middle childhood sibling pairs (age 5-11.99; 95% CI [0.41,0.85]). Additionally, we observed that common environment explained 31% of variation in BMI in this group (95% CI [0.11,0.5]), with unique environment and error explaining the remaining variance. We failed to detect an influence of genetics or common environment in older sibling pairs (12-18) or pairs spanning childhood and adolescence (large sibling age difference), but home type (adoptive versus birth) was an important predictor of BMI in adolescence. The presence of strong common environment effects during childhood suggests that early interventions at the family level in middle childhood could be effective in mitigating obesity risk in later childhood and adolescence.

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Dataset Information

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

Publications

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

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