Journal of Korean biological nursing science · 2025
Genetic heritability of age at menarche and its association with early menopause in the Korean population: a secondary data analysis.
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Shin Hyerim, Jeon Hye Kyung, Yoo Hae Young
Аннотация
PURPOSE: Age at menarche (AAM) is influenced by genetic and environmental factors and is associated with reproductive health outcomes. Therefore, understanding its genetic basis may help predict risks to women's health. This study aimed to identify genetic variants associated with AAM in the Korean population through a genome-wide association study (GWAS) and investigate the relationship between AAM and early menopause.
METHODS: In total, 6,150,556 single nucleotide polymorphisms (SNPs) were generated from full genotyping data of the Health Examinee and Korea Association Resource cohorts, and analyses were conducted on 40,570 selected participants. A GWAS was performed using linear regression analysis with age and body mass index as covariates. A polygenic risk score (PRS) for AAM was constructed and categorized into quartiles, and logistic regression analysis was conducted to assess the association between the PRS for AAM and early menopause.
RESULTS: The GWAS identified 30 significant SNPs associated with AAM. The most significant SNP was rs314275 (beta = 0.0925, p = 2.74 × 10-12) in the Lin-28 homolog B (LIN28B) gene and the SNP with the largest effect estimate was rs67367692 (beta = 0.1238, p = 5.06 × 10-8) in the matrix metallopeptidase 12 (MMP12) gene. Individuals with a higher PRS for AAM showed an increased risk of early menopause.
CONCLUSION: Genetic determinants influence AAM and early menopause in the Korean population. These findings suggest that the genetic factors contributing to late menarche may also increase the risk of early menopause, highlighting the importance of considering genetic risks in women's health strategies.
METHODS: In total, 6,150,556 single nucleotide polymorphisms (SNPs) were generated from full genotyping data of the Health Examinee and Korea Association Resource cohorts, and analyses were conducted on 40,570 selected participants. A GWAS was performed using linear regression analysis with age and body mass index as covariates. A polygenic risk score (PRS) for AAM was constructed and categorized into quartiles, and logistic regression analysis was conducted to assess the association between the PRS for AAM and early menopause.
RESULTS: The GWAS identified 30 significant SNPs associated with AAM. The most significant SNP was rs314275 (beta = 0.0925, p = 2.74 × 10-12) in the Lin-28 homolog B (LIN28B) gene and the SNP with the largest effect estimate was rs67367692 (beta = 0.1238, p = 5.06 × 10-8) in the matrix metallopeptidase 12 (MMP12) gene. Individuals with a higher PRS for AAM showed an increased risk of early menopause.
CONCLUSION: Genetic determinants influence AAM and early menopause in the Korean population. These findings suggest that the genetic factors contributing to late menarche may also increase the risk of early menopause, highlighting the importance of considering genetic risks in women's health strategies.