Cross-trait multivariate GWAS confirms health implications of pubertal timing
Abstract Pubertal timing is highly variable and is associated with long-term health outcomes. Phenotypes associated with pubertal timing include age at menarche, age at voice break, age at first facial hair and growth spurt, and pubertal timing seems to have a shared genetic architecture between the...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56191-4 |
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| author | Siquan Zhou Yujie Xu Jingyuan Xiong Guo Cheng |
| author_facet | Siquan Zhou Yujie Xu Jingyuan Xiong Guo Cheng |
| author_sort | Siquan Zhou |
| collection | DOAJ |
| description | Abstract Pubertal timing is highly variable and is associated with long-term health outcomes. Phenotypes associated with pubertal timing include age at menarche, age at voice break, age at first facial hair and growth spurt, and pubertal timing seems to have a shared genetic architecture between the sexes. However, puberty phenotypes have primarily been assessed separately, failing to account for shared genetics, which limits the reliability of the purported health implications. Here, we model the common genetic architecture for puberty timing using a multivariate GWAS, with an effective population of 514,750 European participants. We find 266 independent variants in 197 loci, including 18 novel variants. Transcriptomic, proteome imputation and fine-mapping analyses reveal genes causal for pubertal timing, including KDM4C, LEPR, CCNC, ACP1, and PCSK1. Linkage disequilibrium score regression and Mendelian randomisation analysis establish causal associations between earlier puberty and both accelerated ageing and the risk of developing cardiovascular disease and osteoporosis. We find that alanine aminotransferase, glycated haemoglobin, high-density lipoprotein cholesterol and Parabacteroides levels are mediators of these relationships, and establish that controlling oily fish and retinol intake may be beneficial for promoting healthy pubertal development. |
| format | Article |
| id | doaj-art-7de748bbe2bf49f0aaa568f8a1da4f5b |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-7de748bbe2bf49f0aaa568f8a1da4f5b2025-01-19T12:32:16ZengNature PortfolioNature Communications2041-17232025-01-0116111410.1038/s41467-025-56191-4Cross-trait multivariate GWAS confirms health implications of pubertal timingSiquan Zhou0Yujie Xu1Jingyuan Xiong2Guo Cheng3West China School of Public Health and West China Fourth Hospital, Sichuan UniversityLaboratory of Molecular Translational Medicine, Center for Translational Medicine, West China Second University Hospital, Sichuan UniversityWest China School of Public Health and West China Fourth Hospital, Sichuan UniversityLaboratory of Molecular Translational Medicine, Center for Translational Medicine, West China Second University Hospital, Sichuan UniversityAbstract Pubertal timing is highly variable and is associated with long-term health outcomes. Phenotypes associated with pubertal timing include age at menarche, age at voice break, age at first facial hair and growth spurt, and pubertal timing seems to have a shared genetic architecture between the sexes. However, puberty phenotypes have primarily been assessed separately, failing to account for shared genetics, which limits the reliability of the purported health implications. Here, we model the common genetic architecture for puberty timing using a multivariate GWAS, with an effective population of 514,750 European participants. We find 266 independent variants in 197 loci, including 18 novel variants. Transcriptomic, proteome imputation and fine-mapping analyses reveal genes causal for pubertal timing, including KDM4C, LEPR, CCNC, ACP1, and PCSK1. Linkage disequilibrium score regression and Mendelian randomisation analysis establish causal associations between earlier puberty and both accelerated ageing and the risk of developing cardiovascular disease and osteoporosis. We find that alanine aminotransferase, glycated haemoglobin, high-density lipoprotein cholesterol and Parabacteroides levels are mediators of these relationships, and establish that controlling oily fish and retinol intake may be beneficial for promoting healthy pubertal development.https://doi.org/10.1038/s41467-025-56191-4 |
| spellingShingle | Siquan Zhou Yujie Xu Jingyuan Xiong Guo Cheng Cross-trait multivariate GWAS confirms health implications of pubertal timing Nature Communications |
| title | Cross-trait multivariate GWAS confirms health implications of pubertal timing |
| title_full | Cross-trait multivariate GWAS confirms health implications of pubertal timing |
| title_fullStr | Cross-trait multivariate GWAS confirms health implications of pubertal timing |
| title_full_unstemmed | Cross-trait multivariate GWAS confirms health implications of pubertal timing |
| title_short | Cross-trait multivariate GWAS confirms health implications of pubertal timing |
| title_sort | cross trait multivariate gwas confirms health implications of pubertal timing |
| url | https://doi.org/10.1038/s41467-025-56191-4 |
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