Identical and Nonidentical Twins: Risk and Factors Involved in Development of Islet Autoimmunity and Type 1 Diabetes
Article Figures & Tables
Figures
- Figure 1
Development of autoantibodies by sibling status: development of GADA (A), development of IA-2A (B), and development of IAA (C). FS, full siblings; IT, identical twins; NT, nonidentical twins.
- Figure 2
Development of type 1 diabetes (T1D) by initial autoantibody status: autoantibody negative (A), single autoantibody positive (B), and multiple autoantibody positive (C). FS, full siblings; IT, identical twins; NT, nonidentical twins.
Tables
- Table 1
Prevalence and autoantibody outcomes at screening by sibling status (N = 48,026)
IT (%) NT (%) FS (%) IT vs. NT OR (95% CI) P value (IT vs. NT) NT vs. FS OR (95% CI) P value (NT vs. FS) GADA 20.2 5.6 4.7 4.31 (2.76–6.73) <0.0001 0.84 (0.59–1.18) 0.302 IA-2A 9.4 3.3 2.2 3.01 (1.67–5.42) 0.0001 1.52 (0.98–2.36) 0.06 IAA 11.9 4.6 2.5 2.78 (1.66–4.67) <0.0001 1.92 (1.32–2.81) 0.0005 ≥1 positive Ab 23.3 8.3 6.2 3.39 (2.28–5.02) <0.0001 1.36 (1.02–1.80) 0.0365 ≥2 positive Ab 12.9 4.0 2.4 3.58 (2.11–6.08) <0.0001 1.72 (1.15–2.58) 0.0079 Both IA-2A and IAA positive 5.9 2.1 0.9 2.99 (1.43–6.24) 0.0023 2.23 (1.28–3.89) 0.0038 Ab, islet autoantibody; FS, full siblings; IT, identical twins; NT, nonidentical twins.
- Table 2
Effects of genetic and environmental factors on autoantibody outcomes (N = 47,729)
Covariate OR (95% CI) P value GADA as outcome Age 1.00 (0.995–1.005) 0.9664 Genetic factors (G) 33.89 (11.54–99.48) <0.0001 Environmental factors (E) 0.922 (0.614–1.385) 0.697 Sex (female) 0.97 (0.89–1.05) 0.453 IA-2A as outcome Age 0.97 (0.96–0.98) <0.0001 Genetic factors (G) 16.82 (4.10–69.72) 0.0001 Environmental factors (E) 1.19 (0.71–2.00) 0.521 Sex (female) 0.79 (0.70–0.89) 0.0001 IAA as outcome Age 0.95 (0.94–0.96) <0.0001 Genetic factors (G) 15.28 (4.37–53.49) <0.0001 Environmental factors (E) 1.48 (0.95–2.32) 0.085 Sex (female) 0.75 (0.67–0.84) <0.0001 ≥1 positive autoantibody as outcome Age 1.00 (0.99–1.00) 0.033 Genetic factors (G) 19.78 (7.64–51.21) <0.0001 Environmental factors (E) 1.07 (0.77–1.51) 0.681 Sex (female) 0.89 (0.83–0.96) 0.002 ≥2 positive autoantibodies as outcome Age 0.96 (0.95–0.97) <0.0001 Genetic factors (G) 26.68 (7.43–95.84) <0.0001 Environmental factors (E) 1.28 (0.80–2.07) 0.307 Sex (female) 0.82 (0.73–0.92) 0.0008 Both IA-2A and IAA positive as outcome Age 0.92 (0.91–0.94) <0.0001 Genetic factors (G) 19.61 (3.29–116.87) 0.0011 Environmental factors (E) 1.67 (0.86–3.23) 0.1286 Sex (female) 0.67 (0.57–0.83) <0.0001 Logistic regression models testing the association of autoantibody outcomes, G (average fraction of genes shared identical by descent with affected proband), and E (environmental factors unique to twins [i.e., shared uterine environment]) adjusted for age and sex.
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