Associations between the pubertal timing-related variant in LIN28B and BMI vary across the life course

Abstract

Context: The common C allele of rs314276 in LIN28B has been robustly associated with earlier age at menarche in girls and associated with earlier timing of other pubertal traits in both sexes.

Objective: Our objective was to explore the associations between rs314276, as a marker of earlier pubertal timing, and body mass index (BMI), weight, and height across the life course.

Methods: The rs314276 in LIN28B was genotyped in 1242 men and 1209 women born in 1946 and participating in the Medical Research Council National Survey of Health and Development. Birth weight was recorded, and height and weight were measured or self-reported repeatedly at 11 time points between ages 2 and 53 yr. Polynomial mixed models were used to test whether additive genetic associations with sd scores (SDS) for BMI and height changed with age between 0 and 53 yr.

Results: Longitudinal analyses revealed age-dependent associations between rs314276 genotype and BMI (P < 0.001 for genotype-by-age(2) interaction) and body weight (P < 0.001 for genotype-by-age(2) interaction) in women, but not in men. In women only, the C allele at rs314276 was associated with higher BMI SDS from ages 15-43 yr. In contrast, C allele associations with shorter height SDS were apparent in both men and women and did not vary with age.

Conclusion: A common genetic variant in LIN28B that confers earlier puberty was associated with a prolonged increase in BMI during adolescence and early to mid-adulthood in women only. Such genetic associations may provide insights into the direct effects of pubertal timing on obesity risk.

Figures

FIG. 1

Cross-sectional associations between LIN28B rs314276 genotype with BMI, weight, and height SDS at up to 12 different time points from birth to age 53 yr in men and women. Error bars represent mean (95% CI) regression coefficient from additive genetic models.