PMID- 35799271 OWN - NLM STAT- MEDLINE DCOM- 20220711 LR - 20220727 IS - 1868-7083 (Electronic) IS - 1868-7075 (Print) IS - 1868-7075 (Linking) VI - 14 IP - 1 DP - 2022 Jul 7 TI - Relative contributions of six lifestyle- and health-related exposures to epigenetic aging: the Coronary Artery Risk Development in Young Adults (CARDIA) Study. PG - 85 LID - 10.1186/s13148-022-01304-9 [doi] LID - 85 AB - BACKGROUND: DNA methylation-based GrimAge acceleration (GrimAA) is associated with a wide range of age-related health outcomes including cardiovascular disease. Since DNA methylation is modifiable by external and behavioral exposures, it is important to identify which of these exposures may have the strongest contributions to differences in GrimAA, to help guide potential intervention strategies. Here, we assessed the relative contributions of lifestyle- and health-related components, as well as their collective association, to GrimAA. RESULTS: We included 744 participants (391 men and 353 women) from the Coronary Artery Risk Development in Young Adults (CARDIA) study with blood DNA methylation information at CARDIA Exam Year (Y) 20 (2005-2006, mean age 45.9 years). Six cumulative exposures by Y20 were included in the analysis: total packs of cigarettes, total alcohol consumption, education years, healthy diet score, sleep hours, and physical activity. We used quantile-based g-computation (QGC) and Bayesian kernel machine regression (BKMR) methods to assess the relative contribution of each exposure to a single overall association with GrimAA. We also assessed the collective association of the six components combined with GrimAA. Smoking showed the greatest positive contribution to GrimAA, accounting for 83.5% of overall positive associations of the six exposures with GrimAA (QGC weight = 0.835). The posterior inclusion probability (PIP) of smoking also achieved the highest score of 1.0 from BKMR analysis. Healthy diet and education years showed inverse contributions to GrimAA. We observed a U-shaped pattern in the contribution of alcohol consumption to GrimAA. While smoking was the greatest contributor across sex and race subgroups, the relative contributions of other components varied by subgroups. CONCLUSIONS: Smoking, alcohol consumption, and education showed the highest contributions to GrimAA in our study. Higher amounts of smoking and alcohol consumption were likely to contribute to greater GrimAA, whereas achieved education was likely to contribute to lower GrimAA. Identifying pertinent lifestyle- and health-related exposures in a context of collective components can provide direction for intervention strategies and suggests which components should be the primary focus for promoting younger GrimAA. CI - (c) 2022. The Author(s). FAU - Kim, Kyeezu AU - Kim K AD - Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, 680 Lake Shore Drive, Suite 1400, Chicago, IL, 60611, USA. FAU - Zheng, Yinan AU - Zheng Y AD - Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, 680 Lake Shore Drive, Suite 1400, Chicago, IL, 60611, USA. FAU - Joyce, Brian T AU - Joyce BT AD - Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, 680 Lake Shore Drive, Suite 1400, Chicago, IL, 60611, USA. FAU - Jiang, Hongmei AU - Jiang H AD - Department of Statistics, Northwestern University, Evanston, IL, USA. FAU - Greenland, Philip AU - Greenland P AD - Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, 680 Lake Shore Drive, Suite 1400, Chicago, IL, 60611, USA. FAU - Jacobs, David R Jr AU - Jacobs DR Jr AD - Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN, USA. FAU - Zhang, Kai AU - Zhang K AD - Department of Environmental Health Sciences, University at Albany, State University of New York, Rensselaer, NY, USA. FAU - Liu, Lei AU - Liu L AD - Division of Biostatistics, Washington University in St. Louis, St. Louis, MO, USA. FAU - Allen, Norrina B AU - Allen NB AD - Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, 680 Lake Shore Drive, Suite 1400, Chicago, IL, 60611, USA. FAU - Wilkins, John T AU - Wilkins JT AD - Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, 680 Lake Shore Drive, Suite 1400, Chicago, IL, 60611, USA. FAU - Forrester, Sarah N AU - Forrester SN AD - Department of Population and Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, MA, USA. FAU - Lloyd-Jones, Donald M AU - Lloyd-Jones DM AD - Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, 680 Lake Shore Drive, Suite 1400, Chicago, IL, 60611, USA. FAU - Hou, Lifang AU - Hou L AD - Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, 680 Lake Shore Drive, Suite 1400, Chicago, IL, 60611, USA. l-hou@northwestern.edu. LA - eng GR - R21 AG068955/AG/NIA NIH HHS/United States GR - HHSN268201800005I/HL/NHLBI NIH HHS/United States GR - HHSN268201800007I/HL/NHLBI NIH HHS/United States GR - HHSN268201800003I/HL/NHLBI NIH HHS/United States GR - HHSN268201800006I/HL/NHLBI NIH HHS/United States GR - HHSN268201800004I/HL/NHLBI NIH HHS/United States GR - R01 DK106201/DK/NIDDK NIH HHS/United States GR - R21 AG068955/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, N.I.H., Intramural PT - Research Support, Non-U.S. Gov't DEP - 20220707 PL - Germany TA - Clin Epigenetics JT - Clinical epigenetics JID - 101516977 SB - IM MH - Aging MH - Bayes Theorem MH - *Coronary Vessels MH - *DNA Methylation MH - Epigenesis, Genetic MH - Female MH - Humans MH - Life Style MH - Male MH - Middle Aged MH - Risk Factors MH - Young Adult PMC - PMC9264709 OTO - NOTNLM OT - Accelerated epigenetic age OT - DNA methylation OT - Epigenetic aging OT - Lifestyle- and health-related components COIS- The authors declare no competing interests. EDAT- 2022/07/08 06:00 MHDA- 2022/07/12 06:00 PMCR- 2022/07/07 CRDT- 2022/07/07 23:51 PHST- 2022/03/24 00:00 [received] PHST- 2022/06/21 00:00 [accepted] PHST- 2022/07/07 23:51 [entrez] PHST- 2022/07/08 06:00 [pubmed] PHST- 2022/07/12 06:00 [medline] PHST- 2022/07/07 00:00 [pmc-release] AID - 10.1186/s13148-022-01304-9 [pii] AID - 1304 [pii] AID - 10.1186/s13148-022-01304-9 [doi] PST - epublish SO - Clin Epigenetics. 2022 Jul 7;14(1):85. doi: 10.1186/s13148-022-01304-9.