Loss of Cardio-Protective Effects at the CDH13 Locus Due to Gene-Sleep Interaction: The BCAMS Study

EBioMedicine. 2018 Jun:32:164-171. doi: 10.1016/j.ebiom.2018.05.033. Epub 2018 Jun 12.

Abstract

Left ventricular mass index (LVMI) provides a metric for cardiovascular disease risk. We aimed to assess the association of adiponectin-related genetic variants resulting from GWAS in East Asians (loci in/near CDH13, ADIPOQ, WDR11FGF, CMIP and PEPD) with LVMI, and to examine whether sleep duration modified these genetic associations in youth. The 559 subjects aged 15-28 years were recruited from the Beijing Child and Adolescent Metabolic Syndrome study. Among the six loci, CDH13 rs4783244 was significantly correlated with adiponectin levels (p = 8.07 × 10-7). The adiponectin-rising allele in rs4783244 locus was significantly associated with decreased LVMI (p = 6.99 × 10-4) after adjusting for classical cardiovascular risk factors, and further for adiponectin levels, while no significant association was found between the other loci and LVMI. Moreover, we observed a significant interaction effect between rs4783244 and sleep duration (p = .005) for LVMI; the genetic association was more evident in long sleep duration while lost in short sleep duration. Similar interaction was found in the subgroup analysis using longitudinal data (p = .025 for interaction). In this young Chinese population, CDH13 rs4783244 represents a key locus for cardiac structure, and confers stronger cardio-protection in longer sleep duration when contrasted with short sleep duration.

Keywords: Adiponectin; Adiponectin-associated locus; CDH13; Left ventricular mass index; Sleep time.

MeSH terms

  • Adolescent
  • Adult
  • Cadherins / genetics*
  • Cardiovascular Diseases / genetics*
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / pathology
  • Female
  • Genetic Association Studies
  • Heart Ventricles / anatomy & histology
  • Heart Ventricles / metabolism*
  • Humans
  • Male
  • Metabolic Syndrome / genetics*
  • Metabolic Syndrome / metabolism
  • Metabolic Syndrome / pathology
  • Risk Factors
  • Sleep / genetics
  • Young Adult

Substances

  • Cadherins
  • H-cadherin