通讯作者地址：[Li, SX]Childrens Hosp & Clin Minnesota, Childrens Minnesota Res Inst, 2525 Chicago Ave,MS 40 LL08, Minneapolis, MN 55404 USA;[Chen, W]Tulane Univ, Sc 更多[Li, SX]Childrens Hosp & Clin Minnesota, Childrens Minnesota Res Inst, 2525 Chicago Ave,MS 40 LL08, Minneapolis, MN 55404 USA;[Chen, W]Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, 1440 Canal St,Room 1504G, New Orleans, LA 70112 USA. 收起
来源：CIRCULATION RESEARCH
出版年：2019
卷：125
期：9
页码：824-833
DOI：10.1161/CIRCRESAHA.119.315397
关键词：body mass index; causality; DNA methylation; epigenomics; longitudinal; studies; obesity; race factors
摘要：Rationale: Previous EWASs (Epigenome-Wide Association Studies) suggest that obesity may be the cause, not a consequence, of changes in DNA methylation (DNAm). However, longitudinal observations are lacking. Objective: To identify 5 '-cytosine-phosphate-guanine-3 ' in DNA (CpG) sites associated with body mass index (BMI) and examine the temporal relationship between dynamic changes in DNAm and BMI in a longitudinal cohort. Methods and Results: Race-specific EWASs were performed in 995 whites and 490 blacks from the Bogalusa Heart Study. Suggestive CpG sites were further replicated in 252 whites and 228 blacks from the Georgia Stress and Heart Study. Cross-lagged panel analysis was used to examine the temporal relationship between DNAm and BMI in 439 whites and 201 blacks who were examined twice 6.2 years apart. In discovery and replication samples, 349 CpG sites (266 novel) in whites and 36 (21 novel) in blacks were identified to be robustly associated with BMI, with 8 (1 novel) CpG sites overlapping between the 2 races. Cross-lagged panel analyses showed significant unidirectional paths (P-FDR <0.05) from baseline BMI to follow-up DNAm at 18 CpG sites in whites and 7 in blacks; no CpG sites showed significant paths from DNAm at baseline to BMI at follow-up. Baseline BMI was associated with a DNAm score (calculated from DNAm levels at the associated CpG sites) at follow-up (P<0.001 both in blacks and in whites). Conclusions: The findings provide strong evidence that obesity is the cause, not a consequence, of changes in DNAm over time.
