title: Heritability and familiality of type 2 diabetes and related quantitative traits in the Botnia Study.
abstract: OBJECTIVE
  To study the heritability and familiality of type 2 diabetes and related quantitative traits in families from the Botnia Study in Finland.
  
  
  METHODS
  Heritability estimates for type 2 diabetes adjusted for sex, age and BMI are provided for different age groups of type 2 diabetes and for 34 clinical and metabolic traits in 5,810 individuals from 942 families using a variance component model (SOLAR). In addition, family means of these traits and their distribution across families are calculated.
  
  
  RESULTS
  The strongest heritability for type 2 diabetes was seen in patients with age at onset 35-60 years (h (2) = 0.69). However, including patients with onset up to 75 years dropped the h (2) estimates to 0.31. Among quantitative traits, the highest h (2) estimates in all individuals and in non-diabetic individuals were seen for lean body mass (h (2) = 0.53-0.65), HDL-cholesterol (0.52-0.61) and suppression of NEFA during OGTT (0.63-0.76) followed by measures of insulin secretion (insulinogenic index [IG(30)] = 0.41-0.50) and insulin action (insulin sensitivity index [ISI] = 0.37-0.40). In contrast, physical activity showed rather low heritability (0.16-0.18), whereas smoking showed strong heritability (0.57-0.59). Family means of these traits differed two- to fivefold between families belonging to the lowest and highest quartile of the trait (p < 0.00001).
  
  
  CONCLUSIONS
  To detect stronger genetic effects in type 2 diabetes, it seems reasonable to restrict inclusion of patients to those with age at onset 35-60 years. Sequencing of families with extreme quantitative traits could be an important next step in the dissection of the genetics of type 2 diabetes.
authors.affiliation: Department of Clinical Sciences, Diabetes and Endocrinology, CRC, Scania University Hospital Malmoe, Lund University, 20502 Malmoe, Sweden. Peter.Almgren@med.lu.se
authors.forename: P
authors.initials: P
authors.lastname: Almgren
authors.forename: M
authors.initials: M
authors.lastname: Lehtovirta
authors.forename: B
authors.initials: B
authors.lastname: Isomaa
authors.forename: L
authors.initials: L
authors.lastname: Sarelin
authors.forename: M R
authors.initials: MR
authors.lastname: Taskinen
authors.forename: V
authors.initials: V
authors.lastname: Lyssenko
authors.forename: T
authors.initials: T
authors.lastname: Tuomi
authors.forename: L
authors.initials: L
authors.lastname: Groop
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D015992:Body Mass Index; D008076:Cholesterol, HDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology*; D005192:Family Health; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005387:Finland / Q000453:epidemiology; D020022:Genetic Predisposition to Disease; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D009043:Motor Activity; D012306:Risk; D012907:Smoking / Q000235:genetics; D055815:Young Adult
chemical_list: D008076:Cholesterol, HDL; D005230:Fatty Acids, Nonesterified