|Title||Novel associations between blood DNA methylation and body mass index in middle-aged and older adults.|
|Publication Type||Journal Article|
|Year of Publication||2018|
|Authors||Geurts YM, Dugué P-A, Joo JE, Makalic E, Jung C-H, Guan W, Nguyen S, Grove ML, Wong EM, Hodge AM, Bassett JK, FitzGerald LM, Tsimiklis H, Baglietto L, Severi G, Schmidt DF, Buchanan DD, MacInnis RJ, Hopper JL, Pankow JS, Demerath EW, Southey MC, Giles GG, English DR|
|Secondary Authors||Milne RL|
|Journal||Int J Obes (Lond)|
|Date Published||2018 04|
|Keywords||Adult, Aged, Australia, Body Mass Index, Cross-Sectional Studies, DNA, DNA Methylation, Female, Gene Regulatory Networks, Genome-Wide Association Study, Humans, Male, Middle Aged, Neoplasms|
BACKGROUND/OBJECTIVES: There is increasing evidence of a relationship between blood DNA methylation and body mass index (BMI). We aimed to assess associations of BMI with individual methylation measures (CpGs) through a cross-sectional genome-wide DNA methylation association study and a longitudinal analysis of repeated measurements over time.
SUBJECTS/METHODS: Using the Illumina Infinium HumanMethylation450 BeadChip, DNA methylation measures were determined in baseline peripheral blood samples from 5361 adults recruited to the Melbourne Collaborative Cohort Study (MCCS) and selected for nested case-control studies, 2586 because they were subsequently diagnosed with cancer (cases) and 2775 as controls. For a subset of 1088 controls, these measures were repeated using blood samples collected at wave 2 follow-up, a median of 11 years later; weight was measured at both time points. Associations between BMI and blood DNA methylation were assessed using linear mixed-effects regression models adjusted for batch effects and potential confounders. These were applied to cases and controls separately, with results combined through fixed-effects meta-analysis.
RESULTS: Cross-sectional analysis identified 310 CpGs associated with BMI with P
CONCLUSIONS: Together, these findings suggest that BMI is associated with blood DNA methylation at a large number of CpGs across the genome, several of which are located in or near genes involved in ATP-binding cassette transportation, tumour necrosis factor signalling, insulin resistance and lipid metabolism.
|Alternate Journal||Int J Obes (Lond)|
|Grant List||HHSN268201700001I / HL / NHLBI NIH HHS / United States |
HHSN268201700002I / HL / NHLBI NIH HHS / United States
HHSN268201700003I / HL / NHLBI NIH HHS / United States
HHSN268201700004I / HL / NHLBI NIH HHS / United States
HHSN268201700005I / HL / NHLBI NIH HHS / United States
RC2 HL102419 / HL / NHLBI NIH HHS / United States
/ RA / ARRA NIH HHS / United States