Differential Impact of Genetic Loci on Age at Thelarche and Menarche in Healthy Girls
Research output: Contribution to journal › Journal article › Research › peer-review
Context: Recent genetic studies have identified genetic variants associated with age at pubertal onset. Whereas genome-wide association studies reported associations of several hundred genetic variants with timing of self-reported age at menarche, a recent clinical study focused on genetic variation affecting follicle-stimulating hormone action and clinically determined age at thelarche. The observations appear to be incongruent, as effect sizes varied substantially among the studies. Alternatively, this may point to a differential impact of specific genetic loci on distinct pubertal events.
Objective: To investigate whether top-candidate genetic variants exhibit a different impact on timing of thelarche vs menarche, respectively.
Design: Cross-sectional and longitudinal study of healthy girls.
Setting: Population-based study in the Copenhagen area.
Patients or Other Participants: Girls (1478) were followed through puberty and genotyped for FSHB c.-211G>T (rs10835638), FSHR c.-29G>A (rs1394205), FSHR c.2039A>G (rs6116), LIN28B (rs7759938), INHA (rs4141153), MKRN3 (rs12148769), TMEM38B (rs10453225), and ZNF483 (rs10980921).
Main Outcome Measures: Clinical pubertal staging and anthropometric data.
Results: We observed an association of LIN28B (rs7759938) with age at thelarche (P < 0.001, effect size: 0.27 year, 95% confidence interval: 0.12 to 0.42) and age at menarche (P = 0.005, 0.17 year, 0.05 to 0.29). FSHB c.-211G>T (rs10835638) and FSHR c.-29G>A (rs1394205) minor allele count was associated with age at thelarche (P = 0.004, 0.19 year, 0.06 to 0.31) but not with age at menarche (P = 0.97; all adjusted for body mass index z scores).
Conclusion: Our results indicate a differential impact of specific genetic loci on age at thelarche and menarche in healthy girls.
Original language | English |
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Journal | The Journal of clinical endocrinology and metabolism |
Volume | 103 |
Issue number | 1 |
Pages (from-to) | 228-234 |
ISSN | 0021-972X |
DOIs | |
Publication status | Published - 2018 |
- Adolescent, Biomarkers/analysis, Child, Child, Preschool, Cross-Sectional Studies, Female, Follow-Up Studies, Genetic Loci, Genetic Variation, Genome-Wide Association Study, Genotype, Humans, Longitudinal Studies, Prognosis, Puberty/genetics
Research areas
ID: 215784180