Loss of Cardio-Protective Effects at the CDH13 Locus Due to Gene-Sleep Interaction: The BCAMS Study
Ge Li,
Dan Feng,
Yonghui Wang,
Junling Fu,
Lanwen Han,
Lujiao Li,
Struan F.A. Grant,
Mingyao Li,
Ming Li,
Shan Gao
Affiliations
Ge Li
Department of Endocrinology, Key Laboratory of Endocrinology, National Health and Family Planning Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing 100730, China
Dan Feng
Department of Endocrinology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100043, China
Yonghui Wang
Department of Endocrinology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100043, China
Junling Fu
Department of Endocrinology, Key Laboratory of Endocrinology, National Health and Family Planning Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing 100730, China
Lanwen Han
Department of Endocrinology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100043, China
Lujiao Li
Department of Endocrinology, Key Laboratory of Endocrinology, National Health and Family Planning Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing 100730, China
Struan F.A. Grant
Division of Endocrinology, The Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA; Division of Human Genetics, The Children's Hospital of Philadelphia Research Institute, Philadelphia, PA 19104, USA; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Mingyao Li
Departments of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA 19104, USA
Ming Li
Department of Endocrinology, Key Laboratory of Endocrinology, National Health and Family Planning Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing 100730, China; Corresponding authors.
Shan Gao
Department of Endocrinology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100043, China; Corresponding authors.
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-associated locus, CDH13, Adiponectin, Left ventricular mass index, Sleep time
