Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
Ollikainen Miina; Hemani Gibran; Rotter Jerome I.; Sillanpaa Elina; Arnett Donna; Uitterlinden Andre G.; Peters Annette; Relton Caroline L.; Matias-Garcia Pamela R.; Walker Rosie M.; Kardia Sharon L. R.; Yao Jie; Zhao Wei; Kaprio Jaakko; Reiner Alex P.; Tsai Pei-Chien; van der Zee Matthijs D.; Moore Ann Zenobia; Murabito Joanne M.; Taylor Jack A.; Deary Ian J.; Lohoff Falk W.; Milne Roger L.; van den Berg David J.; Jeong Ayoung; McCartney Daniel L.; Sun Dianjianyi; Patki Amit; Katrinli Seyma; Soerensen Mette; Kresovich Jacob K.; Gieger Christian; Kuo Pei-Lun; Pedersen Nancy L.; Yet Idil; Palviainen Teemu; Min Josine L.; Wright John; Lawlor Deborah A.; Ferrucci Luigi; Smith Jennifer A.; Southey Melissa C.; Hagg Sara; Waldenberger Melanie; Lu Ake T.; Raffield Laura M.; Xu Zongli; Fornage Myriam; Lehtimaki Terho; Polidoro Silvia; Nygaard Marianne; Porteous David J.; Mangino Massimo; van Meurs Joyce B. J.; Richmond Rebecca C.; Bandinelli Stefania; Correa Adolfo; Horvath Steve; Bell Jordana T.; Davies Gail; de Geus Eco J. C.; Guo Xiuqing; Kahonen Mika; Li Shengxu; Mason Dan; Mishra Pashupati P.; Richardson Tom G.; Raitakari Olli; Christensen Kaare; Mengel-From Jonas; Sobczyk Maria K.; Elliott Hannah R.; McIntosh Andrew M.; Robinson Oliver; Imboden Medea; Tiwari Hemant; van Dongen Jenny; Strauch Konstantin; Ritz Beate; Elliott Paul; Rich Stephen S.; Xia Rui; Conneely Karen N.; Boomsma Dorret I.; Kasela Silva; Sandler Dale P.; Wang Xiaochuan; Marioni Riccardo E.; Irvin Marguerite; Wilson James G.; Milani Lili; Jung Jeesun; Tanaka Toshiko; Broer Linda; Wang Yunzhang; Probst-Hensch Nicole; Hayward Caroline; Harris Sarah E.; Durda Peter; Smith Alicia K.; Boerwinkle Eric; Chen Wei; Lunetta Kathryn L.; Tillin Therese; Ratliff Scott M.; Binder Alexandra M.; Vineis Paolo; Dugue Pierre-Antoine; Pankow James S.
https://urn.fi/URN:NBN:fi-fe2021093048172
Tiivistelmä
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.
Kokoelmat
- Rinnakkaistallenteet [19207]