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- Title
A Peripheral Blood DNA Methylation Signature of Hepatic Fat Reveals a Potential Causal Pathway for Nonalcoholic Fatty Liver Disease.
- Authors
Hennein, Rachel; Tianxiao Huan; Joehanes, Roby; Levy, Daniel; Ci Song; Mendelson, Michael M.; Jiantao Ma; Chunyu Liu; Long, Michelle T.; Liming Liang; Smith, Jennifer A.; Ratliff, Scott; Wei Zhao; Bielak, Lawrence; Kardia, Sharon L. R.; Peyser, Patricia A.; Alferink, Louise J. M.; Murad, Sarwa Darwish; Hongyan Ning; Lloyd-Jones, Donald M.
- Abstract
Nonalcoholic fatty liver disease (NAFLD) is a risk factor for type 2 diabetes (T2D). We aimed to identify the peripheral blood DNA methylation signature of hepatic fat. We conducted epigenome-wide association studies of hepatic fat in 3,400 European ancestry (EA) participants and in 401 Hispanic ancestry and 724 African ancestry participants from four population-based cohort studies. Hepatic fat was measured using computed tomography or ultrasound imaging and DNA methylation was assessed at >400,000 cytosine-guanine dinucleotides (CpGs) in whole blood or CD14+ monocytes using a commercial array. We identified 22 CpGs associated with hepatic fat in EA participants at a false discovery rate <0.05 (corresponding P = 6.9 × 10-6) with replication at Bonferroni-corrected P < 8.6 × 10-4 Mendelian randomization analyses supported the association of hypomethylation of cg08309687 (LINC00649) with NAFLD (P = 2.5 × 10-4). Hypomethylation of the same CpG was also associated with risk for new-onset T2D (P = 0.005). Our study demonstrates that a peripheral blood-derived DNA methylation signature is robustly associated with hepatic fat accumulation. The hepatic fat-associated CpGs may represent attractive biomarkers for T2D. Future studies are warranted to explore mechanisms and to examine DNA methylation signatures of NAFLD across racial/ethnic groups.
- Subjects
FATTY liver; DNA methylation; FAT; EPIGENOMICS; FALSE discovery rate; TYPE 2 diabetes; ULTRASONIC imaging
- Publication
Diabetes, 2019, Vol 68, Issue 5, p1073
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/DB18-1193