title: Genetic and environmental relationships of metabolic and weight phenotypes to metabolic syndrome and diabetes: the healthy twin study.
abstract: BACKGROUND
  We aimed to examine the relationships, including genetic and environmental correlations, between metabolic and weight phenotypes and factors related to diabetes and metabolic syndrome.
  
  
  METHODS
  Participants of the Healthy Twin Study without diabetes (n=2687; 895 monozygotic and 204 dizygotic twins, and 1588 nontwin family members; mean age, 42.5±13.1 years) were stratified according to body mass index (BMI) (<25 vs. ≥25 kg/m(2)) and metabolic syndrome categories at baseline. The metabolic traits, namely diabetes and metabolic syndrome, metabolic syndrome components, glycated hemoglobin (HbA1c) level, and homeostasis model assessment of insulin resistance (HOMA-IR), were assessed after 2.5±2.1 years.
  
  
  RESULTS
  In a multivariate-adjusted model, those who had metabolic syndrome or overweight phenotypes at baseline were more likely to have higher HbA1C and HOMA-IR levels and abnormal metabolic syndrome components at follow-up as compared to the metabolically healthy normal weight subgroup. The incidence of diabetes was 4.4-fold higher in the metabolically unhealthy but normal weight individuals and 3.3-fold higher in the metabolically unhealthy and overweight individuals as compared with the metabolically healthy normal weight individuals. The heritability of the metabolic syndrome/weight phenotypes was 0.40±0.03. Significant genetic and environmental correlations were observed between the metabolic syndrome/weight phenotypes at baseline and the metabolic traits at follow-up, except for incident diabetes, which only had a significant common genetic sharing with the baseline phenotypes.
  
  
  CONCLUSIONS
  The genetic and environmental relationships between the metabolic and weight phenotypes at baseline and the metabolic traits at follow-up suggest pleiotropic genetic mechanisms and the crucial role of lifestyle and behavioral factors.
authors.affiliation: 1 Department of Family Medicine, Samsung Medical Center and Center for Clinical Research, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine , Seoul, South Korea .
authors.forename: Yun-Mi
authors.initials: YM
authors.lastname: Song
authors.forename: Joohon
authors.initials: J
authors.lastname: Sung
authors.forename: Kayoung
authors.initials: K
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001835:Body Weight / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism*; D004200:Diseases in Twins / Q000235:genetics / Q000378:metabolism; D005260:Female; D059647:Gene-Environment Interaction; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D010641:Phenotype; D014427:Twins; D055815:Young Adult