Body mass index drives changes in DNA methylation: A longitudinal study

Dianjianyi Sun, Tao Zhang, Shaoyong Su, Guang Hao, Tao Chen, Quan Zhen Li, Lydia Bazzano, Jiang He, Xiaoling Wang, Shengxu Li, Wei Chen

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


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 (PFDR <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.

Original languageEnglish (US)
Pages (from-to)824-833
Number of pages10
JournalCirculation research
Issue number9
StatePublished - Oct 11 2019
Externally publishedYes


  • Body mass index
  • Causality
  • DNA methylation
  • Epigenomics
  • Longitudinal studies
  • Obesity
  • Race factors

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine


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