The role of protective genetic variants in modulating epigenetic aging
<p dir="ltr">Several progeroid syndromes’ causative mutations have been linked to epigenetic age acceleration as measured via several epigenetic clocks. At the same time, several protective variants have also been discovered that can reduce the risk of developing certain age-related...
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2025
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| _version_ | 1864513538110783488 |
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| author | Yosra Bejaoui (8552574) |
| author2 | Luma Srour (22254409) Abeer Qannan (14779192) Junko Oshima (1626) Chadi Saad (5369351) Steve Horvath (28847) Hamdi Mbarek (134997) Nady El Hajj (686554) |
| author2_role | author author author author author author author |
| author_facet | Yosra Bejaoui (8552574) Luma Srour (22254409) Abeer Qannan (14779192) Junko Oshima (1626) Chadi Saad (5369351) Steve Horvath (28847) Hamdi Mbarek (134997) Nady El Hajj (686554) |
| author_role | author |
| dc.creator.none.fl_str_mv | Yosra Bejaoui (8552574) Luma Srour (22254409) Abeer Qannan (14779192) Junko Oshima (1626) Chadi Saad (5369351) Steve Horvath (28847) Hamdi Mbarek (134997) Nady El Hajj (686554) |
| dc.date.none.fl_str_mv | 2025-02-10T09:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1007/s11357-025-01548-2 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/The_role_of_protective_genetic_variants_in_modulating_epigenetic_aging/30233944 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Genetics Unimodal antigeroid syndromes Epigenetic aging Protective variants APOE PCSK9 Progeroid syndromes |
| dc.title.none.fl_str_mv | The role of protective genetic variants in modulating epigenetic aging |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Several progeroid syndromes’ causative mutations have been linked to epigenetic age acceleration as measured via several epigenetic clocks. At the same time, several protective variants have also been discovered that can reduce the risk of developing certain age-related disorders. However, the impact of these protective variants on epigenetic aging has not been well elucidated. Our research, which involved screening over 14,669 healthy individuals enrolled in the Qatar BioBank (QBB) and sequenced by the Qatar Genome Project (QGP), identified individuals carrying protective variants against age-related disorders, including Alzheimer’s disease (AD), type 2 diabetes (T2D), and atherosclerosis. In this study, we measured methylation levels in blood DNA using the EPIC v2 arrays. In addition, epigenetic age was calculated using various epigenetic clocks. Our analysis revealed that the APOE*E2 protective variant reduces the rate of GrimAge epigenetic aging when compared to individuals with the APOE4 AD risk allele. Furthermore, our differential DNA methylation analysis discovered the association of the <i>PCSK9</i> protective variant with specific biological processes related to immune function and the cardiovascular system. In conclusion, APOE*E2 protective variants have a positive impact on epigenetic aging, while <i>PCSK9</i> protective variants have a significant effect on DNA methylation signatures. Further studies are needed to better understand the underlying mechanisms by which protective variants influence epigenetic aging, particularly the role of APOE*E2 protective variants in biological aging. Furthermore, additional research is required to fully uncover the processes that might enable specific targeted therapies to mimic the effects of beneficial mutations, such as LOF variants in <i>PCSK9</i>, in reducing the risk of geriatric disorders.</p><h2>Other Information</h2><p dir="ltr">Published in: GeroScience<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1007/s11357-025-01548-2" target="_blank">https://dx.doi.org/10.1007/s11357-025-01548-2</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_983b753b6c130cd453bd09cbc1d1ca75 |
| identifier_str_mv | 10.1007/s11357-025-01548-2 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/30233944 |
| publishDate | 2025 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | The role of protective genetic variants in modulating epigenetic agingYosra Bejaoui (8552574)Luma Srour (22254409)Abeer Qannan (14779192)Junko Oshima (1626)Chadi Saad (5369351)Steve Horvath (28847)Hamdi Mbarek (134997)Nady El Hajj (686554)Biological sciencesGeneticsUnimodal antigeroid syndromesEpigenetic agingProtective variantsAPOEPCSK9Progeroid syndromes<p dir="ltr">Several progeroid syndromes’ causative mutations have been linked to epigenetic age acceleration as measured via several epigenetic clocks. At the same time, several protective variants have also been discovered that can reduce the risk of developing certain age-related disorders. However, the impact of these protective variants on epigenetic aging has not been well elucidated. Our research, which involved screening over 14,669 healthy individuals enrolled in the Qatar BioBank (QBB) and sequenced by the Qatar Genome Project (QGP), identified individuals carrying protective variants against age-related disorders, including Alzheimer’s disease (AD), type 2 diabetes (T2D), and atherosclerosis. In this study, we measured methylation levels in blood DNA using the EPIC v2 arrays. In addition, epigenetic age was calculated using various epigenetic clocks. Our analysis revealed that the APOE*E2 protective variant reduces the rate of GrimAge epigenetic aging when compared to individuals with the APOE4 AD risk allele. Furthermore, our differential DNA methylation analysis discovered the association of the <i>PCSK9</i> protective variant with specific biological processes related to immune function and the cardiovascular system. In conclusion, APOE*E2 protective variants have a positive impact on epigenetic aging, while <i>PCSK9</i> protective variants have a significant effect on DNA methylation signatures. Further studies are needed to better understand the underlying mechanisms by which protective variants influence epigenetic aging, particularly the role of APOE*E2 protective variants in biological aging. Furthermore, additional research is required to fully uncover the processes that might enable specific targeted therapies to mimic the effects of beneficial mutations, such as LOF variants in <i>PCSK9</i>, in reducing the risk of geriatric disorders.</p><h2>Other Information</h2><p dir="ltr">Published in: GeroScience<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1007/s11357-025-01548-2" target="_blank">https://dx.doi.org/10.1007/s11357-025-01548-2</a></p>2025-02-10T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1007/s11357-025-01548-2https://figshare.com/articles/journal_contribution/The_role_of_protective_genetic_variants_in_modulating_epigenetic_aging/30233944CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/302339442025-02-10T09:00:00Z |
| spellingShingle | The role of protective genetic variants in modulating epigenetic aging Yosra Bejaoui (8552574) Biological sciences Genetics Unimodal antigeroid syndromes Epigenetic aging Protective variants APOE PCSK9 Progeroid syndromes |
| status_str | publishedVersion |
| title | The role of protective genetic variants in modulating epigenetic aging |
| title_full | The role of protective genetic variants in modulating epigenetic aging |
| title_fullStr | The role of protective genetic variants in modulating epigenetic aging |
| title_full_unstemmed | The role of protective genetic variants in modulating epigenetic aging |
| title_short | The role of protective genetic variants in modulating epigenetic aging |
| title_sort | The role of protective genetic variants in modulating epigenetic aging |
| topic | Biological sciences Genetics Unimodal antigeroid syndromes Epigenetic aging Protective variants APOE PCSK9 Progeroid syndromes |