title: CPT1A methylation is associated with plasma adiponectin.
abstract: OBJECTIVE
  Adiponectin, an adipose-secreted protein that has been linked to insulin sensitivity, plasma lipids, and inflammatory patterns, is an established biomarker for metabolic health. Despite clinical relevance and high heritability, the determinants of plasma adiponectin levels remain poorly understood.
  
  
  RESULTS
  We conducted the first epigenome-wide cross-sectional study of adiponectin levels using methylation data on 368,051 cytosine-phosphate-guanine (CpG) sites in CD4+ T-cells from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN, n = 991). We fit linear mixed models, adjusting for age, sex, study site, T-cell purity, and family. We have identified a positive association (regression coefficient ± SE = 0.01 ± 0.001, P = 3.4 × 10-13) between plasma adiponectin levels and methylation of a CpG site in CPT1A, a key player in fatty acid metabolism. The association was replicated (n = 474, P = 0.0009) in whole blood samples from the Amish participants of the Heredity and Phenotype Intervention (HAPI) Heart Study as well as White (n = 592, P = 0.0005) but not Black (n = 243, P = 0.18) participants of the Bogalusa Heart Study (BHS). The association remained significant upon adjusting for BMI and smoking in GOLDN and HAPI but not BHS. We also identified associations between methylation loci in RNF145 and UFM1 and plasma adiponectin in GOLDN and White BHS participants, although the association was not robust to adjustment for BMI or smoking.
  
  
  CONCLUSIONS
  We have identified and replicated associations between several biologically plausible loci and plasma adiponectin. These findings support the importance of epigenetic processes in metabolic traits, laying the groundwork for future translational applications.
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, USA. Electronic address: saslibek@uab.edu.
authors.forename: S
authors.initials: S
authors.lastname: Aslibekyan
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, USA.
authors.forename: A N
authors.initials: AN
authors.lastname: Do
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, USA.
authors.forename: H
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, USA.
authors.forename: S
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Irvin
authors.affiliation: Department of Biostatistics, University of Alabama at Birmingham, USA.
authors.forename: D
authors.initials: D
authors.lastname: Zhi
authors.affiliation: Department of Biostatistics, University of Alabama at Birmingham, USA.
authors.forename: H K
authors.initials: HK
authors.lastname: Tiwari
authors.affiliation: HudsonAlpha Institute for Biotechnology, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Absher
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Shuldiner
authors.affiliation: Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, USA.
authors.forename: T
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, USA.
authors.forename: W
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, USA.
authors.forename: K
authors.initials: K
authors.lastname: Tanner
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, USA.
authors.forename: C
authors.initials: C
authors.lastname: Hong
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, USA; Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, Baltimore, MD, USA.
authors.forename: B D
authors.initials: BD
authors.lastname: Mitchell
authors.affiliation: Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, USA.
authors.forename: G
authors.initials: G
authors.lastname: Berenson
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, USA.
authors.forename: D K
authors.initials: DK
authors.lastname: Arnett
mesh_terms: D052242:Adiponectin / Q000097:blood*; D000328:Adult; D001741:Black or African American / Q000235:genetics; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics*; D018899:CpG Islands; D003430:Cross-Sectional Studies; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D057890:Epigenomics / Q000379:methods; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011506:Proteins / Q000235:genetics; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D011506:Proteins; C502094:UFM1 protein, human; C577474:CPT1A protein, human; D002334:Carnitine O-Palmitoyltransferase
keywords: Adiponectin; Epidemiology; Epigenetics; Methylation