DNA methylation sites in early adulthood characterised by pubertal timing and development: a twin study
Abstract Background Puberty is a highly heritable and variable trait, with environmental factors having a role in its eventual timing and development. Early and late pubertal onset are both associated with various diseases developing later in life, and epigenetic characterisation of pubertal timing...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | Clinical Epigenetics |
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| Online Access: | https://doi.org/10.1186/s13148-023-01594-7 |
| _version_ | 1797630178587836416 |
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| author | Emir Sehovic Stephanie M. Zellers Markus K. Youssef Aino Heikkinen Jaakko Kaprio Miina Ollikainen |
| author_facet | Emir Sehovic Stephanie M. Zellers Markus K. Youssef Aino Heikkinen Jaakko Kaprio Miina Ollikainen |
| author_sort | Emir Sehovic |
| collection | DOAJ |
| description | Abstract Background Puberty is a highly heritable and variable trait, with environmental factors having a role in its eventual timing and development. Early and late pubertal onset are both associated with various diseases developing later in life, and epigenetic characterisation of pubertal timing and development could lead to important insights. Blood DNA methylation, reacting to both genotype and environment, has been associated with puberty; however, such studies are relatively scarce. We investigated peripheral blood DNA methylation profiles (using Illumina 450 K and EPIC platforms) of 1539 young adult Finnish twins associated with pubertal development scale (PDS) at ages 12 and 14 as well as pubertal age (PA). Results Fixed effect meta-analysis of the two platforms on 347,521 CpGs in common identified 58 CpG sites associated (p < 1 × 10−5) with either PDS or PA. All four CpGs associated with PA and 45 CpGs associated with PDS were sex-specific. Thirteen CpGs had a high heritability (h2: 0.51–0.98), while one CpG site (mapped to GET4) had a high shared environmental component accounting for 68% of the overall variance in methylation at the site. Utilising twin discordance analysis, we found 6 CpG sites (5 associated with PDS and 1 with PA) that had an environmentally driven association with puberty. Furthermore, genes with PDS- or PA-associated CpGs were consistently linked to various developmental processes and diseases such as breast, prostate and ovarian cancer, while methylation quantitative trait loci of associated CpG sites were enriched in immune pathways developing during puberty. Conclusions By identifying puberty-associated DNA methylation sites and examining the effects of sex, environment and genetics, we shed light on the intricate interplay between environment and genetics in the context of puberty. Through our comprehensive analysis, we not only deepen the understanding of the significance of both genetic and environmental factors in the complex processes of puberty and its timing, but also gain insights into potential links with disease risks. |
| first_indexed | 2024-03-11T11:03:23Z |
| format | Article |
| id | doaj.art-949276e0bcc442a4ba07dbf843133046 |
| institution | Directory Open Access Journal |
| issn | 1868-7083 |
| language | English |
| last_indexed | 2024-03-11T11:03:23Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Clinical Epigenetics |
| spelling | doaj.art-949276e0bcc442a4ba07dbf8431330462023-11-12T12:21:14ZengBMCClinical Epigenetics1868-70832023-11-0115111710.1186/s13148-023-01594-7DNA methylation sites in early adulthood characterised by pubertal timing and development: a twin studyEmir Sehovic0Stephanie M. Zellers1Markus K. Youssef2Aino Heikkinen3Jaakko Kaprio4Miina Ollikainen5Department of Life Sciences and Systems Biology, University of TurinInstitute for Molecular Medicine Finland, University of HelsinkiLaboratory for Topology and Neuroscience, Brain Mind Institute, EPFLInstitute for Molecular Medicine Finland, University of HelsinkiInstitute for Molecular Medicine Finland, University of HelsinkiInstitute for Molecular Medicine Finland, University of HelsinkiAbstract Background Puberty is a highly heritable and variable trait, with environmental factors having a role in its eventual timing and development. Early and late pubertal onset are both associated with various diseases developing later in life, and epigenetic characterisation of pubertal timing and development could lead to important insights. Blood DNA methylation, reacting to both genotype and environment, has been associated with puberty; however, such studies are relatively scarce. We investigated peripheral blood DNA methylation profiles (using Illumina 450 K and EPIC platforms) of 1539 young adult Finnish twins associated with pubertal development scale (PDS) at ages 12 and 14 as well as pubertal age (PA). Results Fixed effect meta-analysis of the two platforms on 347,521 CpGs in common identified 58 CpG sites associated (p < 1 × 10−5) with either PDS or PA. All four CpGs associated with PA and 45 CpGs associated with PDS were sex-specific. Thirteen CpGs had a high heritability (h2: 0.51–0.98), while one CpG site (mapped to GET4) had a high shared environmental component accounting for 68% of the overall variance in methylation at the site. Utilising twin discordance analysis, we found 6 CpG sites (5 associated with PDS and 1 with PA) that had an environmentally driven association with puberty. Furthermore, genes with PDS- or PA-associated CpGs were consistently linked to various developmental processes and diseases such as breast, prostate and ovarian cancer, while methylation quantitative trait loci of associated CpG sites were enriched in immune pathways developing during puberty. Conclusions By identifying puberty-associated DNA methylation sites and examining the effects of sex, environment and genetics, we shed light on the intricate interplay between environment and genetics in the context of puberty. Through our comprehensive analysis, we not only deepen the understanding of the significance of both genetic and environmental factors in the complex processes of puberty and its timing, but also gain insights into potential links with disease risks.https://doi.org/10.1186/s13148-023-01594-7PubertyTwinsDNA methylationmeQTLHeritabilityYoung adults |
| spellingShingle | Emir Sehovic Stephanie M. Zellers Markus K. Youssef Aino Heikkinen Jaakko Kaprio Miina Ollikainen DNA methylation sites in early adulthood characterised by pubertal timing and development: a twin study Clinical Epigenetics Puberty Twins DNA methylation meQTL Heritability Young adults |
| title | DNA methylation sites in early adulthood characterised by pubertal timing and development: a twin study |
| title_full | DNA methylation sites in early adulthood characterised by pubertal timing and development: a twin study |
| title_fullStr | DNA methylation sites in early adulthood characterised by pubertal timing and development: a twin study |
| title_full_unstemmed | DNA methylation sites in early adulthood characterised by pubertal timing and development: a twin study |
| title_short | DNA methylation sites in early adulthood characterised by pubertal timing and development: a twin study |
| title_sort | dna methylation sites in early adulthood characterised by pubertal timing and development a twin study |
| topic | Puberty Twins DNA methylation meQTL Heritability Young adults |
| url | https://doi.org/10.1186/s13148-023-01594-7 |
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