Identification of loci associated with women’s reproductive traits and exploration of a shared genetic basis with obesity
Abstract Background The timing of menarche and menopause significantly affects women’s health, with influences on cancer, cardiovascular disease, obesity, type 2 diabetes, and psychosocial problems. In addition, observational studies have reported that ages at menarche (AAM) and natural menopause (A...
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2025-05-01
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| Online Access: | https://doi.org/10.1186/s40246-025-00773-2 |
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| author | Seong-ah Kwon Yoon Shin Cho |
| author_facet | Seong-ah Kwon Yoon Shin Cho |
| author_sort | Seong-ah Kwon |
| collection | DOAJ |
| description | Abstract Background The timing of menarche and menopause significantly affects women’s health, with influences on cancer, cardiovascular disease, obesity, type 2 diabetes, and psychosocial problems. In addition, observational studies have reported that ages at menarche (AAM) and natural menopause (ANM) are correlated with obesity. To understand the genetic bases of these reproductive traits, we conducted a genome-wide association study (GWAS) of AAM and ANM in the Korean population. We also investigated the genetic correlation and causal relationship to explore the shared genetic architecture between reproductive traits and obesity in women. Results Our GWA analyses of 45,608 and 21,599 adult women identified two and six genome-wide significant associations (P-value < 5 × 10− 8) for AAM and ANM, respectively. Although most of the loci that we detected have been reported in previous studies, we have newly linked the JHY locus containing the SNP rs11605693 to AAM. Leveraging the GWAS results, we tested the shared genetic basis underlying AAM and ANM, which appear to be closely related to female hormone activity. Linkage disequilibrium score regression (LDSC) analysis did not identify a significant genetic correlation between the two traits. Our LDSC analyses indicated that AAM was inversely correlated with two obesity traits, body mass index (BMI) and waist circumference (WC). However, Mendelian randomization (MR) analyses did not provide evidence of a causal relationship between AAM and obesity traits. Conclusions Overall, our study provides insights into the genetic architecture of women’s reproductive traits and the shared genetic basis between AAM and obesity. Our MR analyses suggest that the genetic correlation between AAM and obesity traits results from the direct effects of genetic variants on both traits rather than a causal relationship between them. |
| format | Article |
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| institution | OA Journals |
| issn | 1479-7364 |
| language | English |
| publishDate | 2025-05-01 |
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| series | Human Genomics |
| spelling | doaj-art-72d885d5ba1b4dfbb36d19ef6bd93ffc2025-08-20T01:53:14ZengBMCHuman Genomics1479-73642025-05-0119111110.1186/s40246-025-00773-2Identification of loci associated with women’s reproductive traits and exploration of a shared genetic basis with obesitySeong-ah Kwon0Yoon Shin Cho1Department of Biomedical Science, Hallym UniversityDepartment of Biomedical Science, Hallym UniversityAbstract Background The timing of menarche and menopause significantly affects women’s health, with influences on cancer, cardiovascular disease, obesity, type 2 diabetes, and psychosocial problems. In addition, observational studies have reported that ages at menarche (AAM) and natural menopause (ANM) are correlated with obesity. To understand the genetic bases of these reproductive traits, we conducted a genome-wide association study (GWAS) of AAM and ANM in the Korean population. We also investigated the genetic correlation and causal relationship to explore the shared genetic architecture between reproductive traits and obesity in women. Results Our GWA analyses of 45,608 and 21,599 adult women identified two and six genome-wide significant associations (P-value < 5 × 10− 8) for AAM and ANM, respectively. Although most of the loci that we detected have been reported in previous studies, we have newly linked the JHY locus containing the SNP rs11605693 to AAM. Leveraging the GWAS results, we tested the shared genetic basis underlying AAM and ANM, which appear to be closely related to female hormone activity. Linkage disequilibrium score regression (LDSC) analysis did not identify a significant genetic correlation between the two traits. Our LDSC analyses indicated that AAM was inversely correlated with two obesity traits, body mass index (BMI) and waist circumference (WC). However, Mendelian randomization (MR) analyses did not provide evidence of a causal relationship between AAM and obesity traits. Conclusions Overall, our study provides insights into the genetic architecture of women’s reproductive traits and the shared genetic basis between AAM and obesity. Our MR analyses suggest that the genetic correlation between AAM and obesity traits results from the direct effects of genetic variants on both traits rather than a causal relationship between them.https://doi.org/10.1186/s40246-025-00773-2Age at menarcheAge at menopauseGenome-wide association studyGenetic correlationMendelian randomization |
| spellingShingle | Seong-ah Kwon Yoon Shin Cho Identification of loci associated with women’s reproductive traits and exploration of a shared genetic basis with obesity Human Genomics Age at menarche Age at menopause Genome-wide association study Genetic correlation Mendelian randomization |
| title | Identification of loci associated with women’s reproductive traits and exploration of a shared genetic basis with obesity |
| title_full | Identification of loci associated with women’s reproductive traits and exploration of a shared genetic basis with obesity |
| title_fullStr | Identification of loci associated with women’s reproductive traits and exploration of a shared genetic basis with obesity |
| title_full_unstemmed | Identification of loci associated with women’s reproductive traits and exploration of a shared genetic basis with obesity |
| title_short | Identification of loci associated with women’s reproductive traits and exploration of a shared genetic basis with obesity |
| title_sort | identification of loci associated with women s reproductive traits and exploration of a shared genetic basis with obesity |
| topic | Age at menarche Age at menopause Genome-wide association study Genetic correlation Mendelian randomization |
| url | https://doi.org/10.1186/s40246-025-00773-2 |
| work_keys_str_mv | AT seongahkwon identificationoflociassociatedwithwomensreproductivetraitsandexplorationofasharedgeneticbasiswithobesity AT yoonshincho identificationoflociassociatedwithwomensreproductivetraitsandexplorationofasharedgeneticbasiswithobesity |