Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
| العنوان: | Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging |
|---|---|
| المؤلفون: | Jacob K. Kresovich, Jerome I. Rotter, James S. Pankow, Laura M. Raffield, André G. Uitterlinden, Hemant K. Tiwari, Dorret I. Boomsma, Marguerite R. Irvin, Kaare Christensen, Lili Milani, Jonas Mengel-From, Scott M. Ratliff, Peter Durda, James G. Wilson, Xiaochuan Wang, Rui Xia, Jordana T. Bell, Jenny van Dongen, Pamela R. Matias-Garcia, Alexander P. Reiner, Andrew M. McIntosh, Toshiko Tanaka, Sharon L.R. Kardia, Rebecca C Richmond, Konstantin Strauch, Rosie M. Walker, Dale P. Sandler, Amit Patki, Teemu Palviainen, Wei Chen, Pei-Chien Tsai, Medea Imboden, Stefania Bandinelli, Mika Kähönen, Xiuqing Guo, Stephen S. Rich, Oliver Robinson, Riccardo E. Marioni, Jie Yao, Debbie A Lawlor, Pierre Antoine Dugué, Roger L. Milne, Yunzhang Wang, Jennifer A. Smith, Nancy L. Pedersen, Matthijs D. van der Zee, Pashupati P. Mishra, Pei-Lun Kuo, Steve Horvath, Miina Ollikainen, Massimo Mangino, Melissa C. Southey, Ayoung Jeong, Linda Broer, Dianjianyi Sun, Tom G. Richardson, David Van Den Berg, Jack A. Taylor, Beate Ritz, Jeesun Jung, Caroline L Relton, Sarah E. Harris, Josine L. Min, Caroline Hayward, Eric Boerwinkle, Jaakko Kaprio, Melanie Waldenberger, David J. Porteous, Seyma Katrinli, Gibran Hemani, Olli T. Raitakari, Paolo Vineis, Silvia Polidoro, Karen N. Conneely, Christian Gieger, Donna K. Arnett, Marianne Nygaard, Maria K. Sobczyk, Therese Tillin, Falk W. Lohoff, Adolfo Correa, Wei Zhao, Elina Sillanpää, Zongli Xu, Joanne M. Murabito, John Wright, Gail Davies, Sara Hägg, Mette Soerensen, Alexandra M. Binder, Ann Zenobia Moore, Eco J. C. de Geus, Terho Lehtimäki, Dan Mason, Daniel L. McCartney, Myriam Fornage, Ian J. Deary, Alicia K. Smith, Joyce B. J. van Meurs, Ake T. Lu, Hannah R Elliott, Annette Peters, Silva Kasela, Idil Yet, Luigi Ferrucci, Shengxu Li, Nicole Probst-Hensch, Paul Elliott, Kathryn L. Lunetta |
| المساهمون: | Tampere University, Department of Clinical Chemistry, Clinical Medicine, Department of Clinical Physiology and Nuclear Medicine, Institute for Molecular Medicine Finland, Genetic Epidemiology, Helsinki Institute of Life Science HiLIFE, Department of Public Health, Medical Research Council (MRC), Home Office, Imperial College Healthcare NHS Trust- BRC Funding, Internal Medicine, Epidemiology, Biological Psychology, APH - Mental Health, APH - Personalized Medicine, APH - Methodology |
| المصدر: | Genome Biology, Vol 22, Iss 1, Pp 1-25 (2021) Genome Biology Mccartney, D L, Min, J L, Richmond, R C, Lu, A T, Sobczyk, M K, Davies, G, Broer, L, Guo, X, Jeong, A, Jung, J, Kasela, S, Katrinli, S, Kuo, P, Matias-garcia, P R, Mishra, P P, Nygaard, M, Palviainen, T, Patki, A, Raffield, L M, Ratliff, S M, Richardson, T G, Robinson, O, Soerensen, M, Sun, D, Tsai, P, Van Der Zee, M D, Walker, R M, Wang, X, Wang, Y, Xia, R, Xu, Z, Yao, J, Zhao, W, Correa, A, Boerwinkle, E, Dugué, P, Durda, P, Elliott, H R, Gieger, C, De Geus, E J C, Harris, S E, Hemani, G, Imboden, M, Kähönen, M, Kardia, S L R, Kresovich, J K, Li, S, Lunetta, K L, Mangino, M, Mason, D, Mcintosh, A M, Mengel-from, J, Moore, A Z, Murabito, J M, Ollikainen, M, Pankow, J S, Pedersen, N L, Peters, A, Polidoro, S, Porteous, D J, Raitakari, O, Rich, S S, Sandler, D P, Sillanpää, E, Smith, A K, Southey, M C, Strauch, K, Tiwari, H, Tanaka, T, Tillin, T, Uitterlinden, A G, Van Den Berg, D J, Van Dongen, J, Wilson, J G, Wright, J, Yet, I, Arnett, D, Bandinelli, S, Bell, J T, Binder, A M, Boomsma, D I, Chen, W, Christensen, K, Conneely, K N, Elliott, P, Ferrucci, L, Fornage, M, Hägg, S, Hayward, C, Irvin, M, Kaprio, J, Lawlor, D A, Lehtimäki, T, Lohoff, F W, Milani, L, Milne, R L, Probst-hensch, N, Reiner, A P, Ritz, B, Rotter, J I, Smith, J A, Taylor, J A, Van Meurs, J B J, Vineis, P, Waldenberger, M, Deary, I J, Relton, C L, Horvath, S & Marioni, R E 2021, ' Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging ', Genome Biology, vol. 22, no. 1 . https://doi.org/10.1186/s13059-021-02398-9Test McCartney, D L, Min, J L, Richmond, R C, Lu, A T, Sobczyk, M K, Davies, G, Broer, L, Guo, X, Jeong, A, Jung, J, Kasela, S, Katrinli, S, Kuo, P L, Matias-Garcia, P R, Mishra, P P, Nygaard, M, Palviainen, T, Patki, A, Raffield, L M, Ratliff, S M, Richardson, T G, Robinson, O, Soerensen, M, Sun, D, Tsai, P C, van der Zee, M D, Walker, R M, Wang, X, Wang, Y, Xia, R, Xu, Z, Yao, J, Zhao, W, Correa, A, Boerwinkle, E, Dugué, P A, Durda, P, Elliott, H R, Gieger, C, de Geus, E J C, Harris, S E, Hemani, G, Imboden, M, Kähönen, M, Kardia, S L R, Kresovich, J K, Li, S, Lunetta, K L, Mengel-From, J, Christensen, K, The Genetics of DNA Methylation Consortium & NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium 2021, ' Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging ', Genome Biology, vol. 22, 194 . https://doi.org/10.1186/s13059-021-02398-9Test McCartney, D L, van der Zee, M D, de Geus, E J C, van Dongen, J, Boomsma, D I, Marioni, R E, The Genetics of DNA Methylation Consortium & NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium 2021, ' Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging ', Genome Biology, vol. 22, no. 1, 194, pp. 1-25 . https://doi.org/10.1186/s13059-021-02398-9Test Genome Biol. 22:194 (2021) McCartney, D L, Min, J L, Richmond, R C, Lu, A T, Sobczyk, M K, Davies, G, Broer, L, Guo, X, Jeong, A, Jung, J, Kasela, S, Katrinli, S, Kuo, P-L, Matias-Garcia, P R, Mishra, P P, Nygaard, M, Palviainen, T, Patki, A, Raffield, L M, Ratliff, S M, Richardson, T G, Robinson, O, Soerensen, M, Sun, D, Tsai, P-C, van der Zee, M D, Walker, R M, Wang, X, Wang, Y, Xia, R, Xu, Z, Yao, J, Zhao, W, Correa, A, Boerwinkle, E, Dugué, P-A, Durda, P, Elliott, H R, Gieger, C, de Geus, E J C, Harris, S E, Hemani, G, Smith, A K, Wright, J, Lawlor, D A, Relton, C L, Horvath, S & Marioni, R E & et, A 2021, ' Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging ', Genome Biology, vol. 22, no. 1, 194, pp. 194 . https://doi.org/10.1186/s13059-021-02398-9Test Genome Biology, 22(1):194. BioMed Central Ltd. Genome Biology, 22(1):194, 1-25. Springer Verlag |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Aging, Multifactorial Inheritance, BLOOD, Epigenetic clock, 05 Environmental Sciences, biomarkkerit, Genome-wide association study, QH426-470, Epigenesis, Genetic, 0302 clinical medicine, Biomarkers of aging, GWAS, Biology (General), Adiposity, Genetics, 11832 Microbiology and virology, 0303 health sciences, 318 Medical biotechnology, DNA methylation, 1184 Genetics, developmental biology, physiology, genomiikka, Dna Methylation, Epigenetic Clock, Gwas, ddc, DNA-metylaatio, INSIGHTS, C-Reactive Protein, epigenetiikka, MENDELIAN RANDOMIZATION, Educational Status, ICEP, Genetic Markers, PROVIDES, SUSCEPTIBILITY LOCI, Bioinformatics, QH301-705.5, Genomics, Biology, 03 medical and health sciences, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, AGE, SDG 3 - Good Health and Well-being, Plasminogen Activator Inhibitor 1, REGRESSION, Humans, Epigenetics, Gene, METAANALYSIS, 030304 developmental biology, Genome, Human, Research, Genetics of DNA Methylation Consortium, 06 Biological Sciences, Lipid Metabolism, Human genetics, Genetic architecture, Immunity, Innate, ikääntyminen, Genetic Loci, CpG Islands, 08 Information and Computing Sciences, 3111 Biomedicine, ENRICHMENT, epigenetic clock, 030217 neurology & neurosurgery, Biomarkers, Genome-Wide Association Study, Granulocytes |
| الوصف: | Background Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Results Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. Conclusion This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity. |
| وصف الملف: | fulltext; application/pdf |
| اللغة: | English |
| تدمد: | 1474-7596 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7d4c22aaef8ad6a80ac07f88cd86c101Test https://trepo.tuni.fi/handle/10024/133417Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7d4c22aaef8ad6a80ac07f88cd86c101 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14747596 |
|---|