Introduction 1 2 3 2 1 4 21 22 23 7 18 22 24 7 10 13 17 21 25 34 1 1 35 Methods Participants 36 p p Electronic Supplementary Material . n Descriptive statistical analysis df F p p 37 Twin model fitting 37 http://www.psy.vu.nl/mxbib/ H 2 5 1 5 Fig. 1 a b c M W M W g c  If for a certain trait the correlation of the opposite-sex pairs is smaller than the correlations for the like-sexed DZ pairs, it is suggested that the correlation between additive genetic factors in opposite-sex pairs is smaller than 0.5. This indicates that different genetic factors influence this trait in men and women. To test this, a full heterogeneity model (variance components free to differ across sexes, plus the correlation between the additive genetic factors in opposite-sex pairs free to be estimated between 0 and 0.5) was compared with a quantitative heterogeneity model. χ 2 χ 2 df df χ 2 p df Results Descriptive statistical analysis 1 1 Table 1 Anthropometric and metabolic characteristics of the twin population according to chorion type for men and women separately in the EFPTS Characteristic Men Women MZ MC MZ DC DZ p  MZ MC MZ DC DZ p  n 134 92 135  142 112 141  a 25.3 ± 4.5 25.0 ± 4.9 25.7 ± 4.7 0.33 25.9 ± 4.4 24.0 ± 4.8 25.7 ± 4.6 0.02 Body height (cm) 178.0 ± 5.7  178.3 ± 7.2 178.4 ± 6.5 0.92 165.0 ± 6.3 165.6 ± 6.1 166.2 ± 6.4 0.59 Body mass (kg) 70.7 ± 10.5 69.6 ± 8.4 70.9 ± 10.2 0.67 60.5 ± 9.7 60.5 ± 10.6 60.8 ± 10.2 0.98 2 22.1 ± 1.1 21.8 ± 1.1 22.1 ± 1.2 0.73 22.0 ± 1.2 21.8 ± 1.2 21.8 ± 1.2 0.86 WHR (%) 83.4 ± 5.4 83.4 ± 5.8 82.8 ± 5.5 0.84 73.4 ± 4.5 73.3 ± 4.6 72.5 ± 4.3 0.30 b 35.9 ± 1.5 34.6 ± 1.5 34.8 ± 1.5 0.89 57.1 ± 1.4 55.6 ± 1.5 53.6 ± 1.4 0.50 b 11.9 ± 1.6 11.2 ± 1.5 12.2 ± 1.5 0.33 16.9 ± 1.3 16.7 ± 1.4 16.8 ± 1.3 0.95 Lean body mass (kg) 57.7 ± 6.9 57.6 ± 6.0 57.7 ± 6.6 0.99 42.9 ± 5.1 43.1 ± 5.6 43.4 ± 6.0 0.89 b 11.0 ± 1.9 10.3 ± 1.8 11.5 ± 1.9 0.46 16.8 ± 2.0  16.6 ± 2.2 18.4 ± 2.3 0.58 b 33.5 ± 1.5  32.7 ± 1.6 32.7 ± 1.6 0.94 38.6 ± 1.5 35.8 ± 1.6 40.1 ± 1.5 0.24 b 1.2 ± 1.6 1.2 ± 1.6 1.2 ± 1.6 0.69 1.3 ± 1.5 1.2 ± 1.7 1.4 ± 1.5 0.26 Fasting glucose (mmol/l) 5.0 ± 0.5 4.9 ± 0.4 4.8 ± 0.4 0.01 4.5 ± 0.3 4.6 ± 0.4 4.6 ± 0.4 0.23 b 77.2 ± 1.5 78.2 ± 1.6 86.5 ± 1.7 0.10 135.2 ± 1.7 115.7 ± 1.6 126.7 ± 1.6 0.17 b 1.7 ± 3.0 1.4 ± 2.9 1.7 ± 3.0 0.42 11.5 ± 2.1 11.2 ± 2.2 11.5 ± 1.9 0.92 Total cholesterol (mmol/l) 4.8 ± 0.9 4.7 ± 1.0 4.9 ± 1.1 0.31 5.3 ± 0.9 4.9 ± 0.8 5.3 ± 1.0 0.006 LDL-cholesterol (mmol/l) 3.0 ± 0.9 2.9 ± 0.9 3.1 ± 1.0 0.35 3.1 ± 0.8 2.7 ± 0.8 2.9 ± 0.8 0.012 HDL-cholesterol (mmol/l) 1.3 ± 0.3 1.3 ± 0.3 1.4 ± 0.4 0.94 1.8 ± 0.4 1.8 ± 0.4 1.9 ± 0.4 0.39 b 3.6 ± 1.4 3.5 ± 1.3 3.7 ± 1.4 0.67 3.0 ± 1.3 2.8 ± 1.3 2.9 ± 1.3 0.34 b 0.9 ± 1.6 0.9 ± 1.5 0.9 ± 1.5 0.78 0.9 ± 1.5 0.9 ± 1.5 0.9 ± 1.5 0.83 NEFA (mmol/l) 0.5 ± 0.2 0.5 ± 0.2 0.5 ± 0.2 0.05 0.7 ± 0.2 0.7 ± 0.3 0.7 ± 0.2 0.81 Data are expressed as mean ± SD HOMA, homeostasis model assessment a p b 2 p 2 Table 2 Intra-pair correlations of MZ MC and MZ DC pairs, and of each sex by zygosity group before and after adjusting for covariates in the EFPTS Characteristic Monozygotic Monozygotic Dizygotic Covariates MC DC Men Women Men Women OS n 138 102 113 127 46 49 43  Body mass  0.85/0.79 0.84/0.76 0.86/0.82 0.76/0.73 0.38/0.28 0.58/0.57 0.26/0.35 Sex, age, height BMI 0.80/0.78 0.81/0.77 0.86/0.83 0.77/0.74 0.46/0.31 0.53/0.56 0.47/0.46 Age WHR 0.87/0.69 0.88/0.71 0.79/0.74 0.70/0.66 0.39/0.28 0.44/0.48 0.31/0.15 Sex, age S4SF 0.82/0.73 0.84/0.75 0.81/0.79 0.72/0.68 0.46/0.37 0.64/0.63 0.36/0.31 Sex, age Fat mass 0.85/0.78 0.85/0.75 0.85/0.82 0.73/0.69 0.46/0.36 0.43/0.46 0.42/0.35 Sex, age Lean body mass 0.93/0.81 0.93/0.79 0.86/0.82 0.79/0.78 0.43/0.39 0.65/0.58 0.25/0.39 Sex, age, height IGFBP-1 0.49/0.39 0.60/0.53 0.55/0.51 0.45/0.43 0.31/0.21 0.08/0.06 0.12/−0.05 Sex, age, BMI Fasting insulin 0.57/0.48 0.52/0.50 0.49/0.45 0.58/0.52 0.07/0.13 0.18/0.19 0.07/−0.01 Age, S4SF Insulin resistance 0.54/0.47 0.53/0.50 0.49/0.46 0.57/0.51 0.03/0.08 0.14/0.17 0.04/−0.05 Sex, age, S4SF Fasting glucose 0.74/0.66 0.73/0.67 0.65/0.65 0.70/0.69 0.28/0.24 0.57/0.60 0.31/0.32 Sex, BMI Beta cell function 0.71/0.58 0.66/0.60 0.52/0.50 0.68/0.66 0.32/0.40 0.47/0.46 0.37/0.33 Sex, age, S4SF Leptin 0.85/0.53 0.85/0.57 0.70/0.58 0.64/0.52 0.35/0.02 0.66/0.31 0.38/0.37 Sex, age, S4SF Total cholesterol 0.76/0.74 0.77/0.72 0.78/0.74 0.73/0.73 0.52/0.51 0.51/0.44 0.63/0.51 Age, S4SF LDL-cholesterol 0.78/0.79 0.81/0.74 0.81/0.79 0.77/0.75 0.52/0.51 0.59/0.52 0.68/0.58 Sex, age, S4SF HDL-cholesterol 0.78/0.71 0.84/0.77 0.75/0.76 0.74/0.74 0.31/0.30 0.44/0.44 0.52/0.52 Sex, S4SF Total cholesterol:HDL-cholesterol ratio 0.81/0.78 0.86/0.81 0.84/0.82 0.78/0.76 0.50/0.41 0.50/0.49 0.65/0.54 Age, WHR Triacylglycerol 0.58/0.56 0.67/0.60 0.59/0.54 0.63/0.60 0.29/0.41 0.34/0.34 0.16/0.17 Sex, S4SF NEFA 0.49/0.35 0.43/0.39 0.39/0.38 0.34/0.37 0.10/0.14 0.20/0.18 0.25/0.26 Sex, S4SF Values are unadjusted intra-pair correlation/adjusted intra-pair correlation. OS, opposite sex Twin model fitting 3 3 Table 3 Variance components estimates and 95% CIs of best-fitting models expressed in percentages Characteristic Unadjusted Adjusted for covariates Model Sex 2  2 2 2  2 2 S Model Sex 2  2 2 2  2 2 S Body mass  AE M 90 (86–93) – – 10 (7–14)  AE M 84 (78–88) – – 16 (12–22)  AE W 80 (73–85) – – 20 (15–27)  AE W 74 (66–80) – – 26 (20–34)  BMI  AE M 87 (82–90) – – 13 (10–18)  AE M 85 (79–89) – – 15 (11–21)  AE W 76 (68–82) – – 24 (18–32)  AE W 75 (67–81) – – 25 (19–33)  WHR AE M 94 (92–96) – – 6 (4–8)  AE  70 (63–75) – – 30 (25–37) M>W AE W 70 (59–77) – – 30 (23–41)         S4SF AE M 88 (83–91) – – 12 (9–17)  AE  74 (68–79) – – 26 (21–32) M>W AE W 75 (67–81) – – 25 (19–33)         Fat mass  AE M 88 (84–92) – – 12 (8–16)  AE M 81 (74–86) – – 19 (14–26)  AE W 74 (65–80) – – 26 (20–35)  AE W 70 (60–77) – – 30 (23–40)  Lean body mass  AE M 97 (96–98) – – 3 (2–4)  AE  81 (76–84) – – 19 (16–24) M>W AE W 82 (76–87) – – 18 (13–24)         IGFBP-1  DE  – – 56 (47–64) 44 (36–53) W>M DE  – – 47 (36–56) 53 (44–64) W>M Fasting insulin  DE  – – 54 (45–62) 46 (38–55)  DE  – – 49 (39–58) 51 (42–61)  Insulin resistance DE  – – 52 (42–60) 48 (40–58)  DE  – – 48 (38–57) 52 (43–62)  Fasting glucose  AE  72 (66–77) – – 28 (23–34) M>W AE  67 (60–73) – – 33 (27–40) M>W Beta cell function  AE  69 (63–75) – – 31 (25–37)  AE  62 (54–69) – – 38 (31–46)  Leptin  AE M 92 (88–94) – – 8 (6–12)  AE  53 (44–61) – – 47 (39–56) M>W AE  W 63 (52–72) – – 37 (28–48)         Total cholesterol  ACE  49 (28–74) 29 (4–48) – 22 (18–28)  AE  75 (69–79) – – 25 (21–31)  LDL-cholesterol  ACE  43 (24–67) 37 (14–54) – 20 (16–25) M>W AE  78 (73–82) – – 22 (18–27)  HDL-cholesterol  AE   82 (78–86) – – 18 (14–22) W>M AE  76 (70–81) – – 24 (19–30) W>M Total cholesterol:HDL-cholesterol ratio AE M 88 (83–91) – – 12 (9–17)  AE  79 (74–83) – – 21 (17–26) M>W AE W 79 (72–85) – – 21 (15–28)         Triacylglycerol AE  61 (52–68) – – 39 (32–48)  AE  58 (49–66) – – 42 (34–51)  NEFA AE  46 (36–54) – – 54 (46–64) W>M AE  37 (25–47) – – 63 (53–75) W>M Values are variance components estimates (95% CI) 2 2 2 2 2 3 3 3 3 2 p 3 3 Discussion 36 38 1 7 15 18 39 4 6 9 20 40 1 1 41 42 H 2 1 42 43 H 2 H 2 H 2 H 2 1 44 45 46 35 H 2 41 47 7 18 22 24 41 43 18 41 43 36 48 49 1 4 50 36 5 12 16 3 In conclusion, this study is the first large study to give a comprehensive overview of the heritabilities of multiple risk factors related to type 2 diabetes within the same twin sample. The variation of traits related to obesity, glucose intolerance/insulin resistance and dyslipidaemia in this Belgian twin sample is in general highly explained by genetic factors. These high heritabilities are very promising for follow-up to this research, in which, in order to explain some of the genetic variance observed, sib-pair linkage analyses will be performed using microsatellite markers located in the close vicinity of selected candidate genes. Electronic supplementary material Below is the link to the electronic supplementary material.
 ESM 1 (PDF 64 kb)