Evidence that BMI and type 2 diabetes share only a minor fraction of genetic variance: a follow-up study of 23,585 monozygotic and dizygotic twins from the Finnish Twin Cohort Study

Abstract

Aims/hypothesis We investigated whether BMI predicts type 2 diabetes in twins and to what extent that is explained by common genetic factors. Methods This was a population-based twin cohort study. Monozygotic (n=4,076) and dizygotic (n=9,109) nondiabetic twin pairs born before 1958 answered a questionnaire in 1975, from which BMI was obtained. Information on incident cases of diabetes was obtained by linkage to nationwide registers until 2005. Results Altogether, 1,332 twins (6.3% of men, 5.1% of women) developed type 2 diabetes. The HR for type 2 diabetes increased monotonically with a mean of 1.22 (95% CI 1.20-1.24) per BMI unit and of 1.97 (95% CI 1.87-2.08) per SD of BMI. The HRs for lean, overweight, obese and morbidly obese participants were 0.59, 2.96, 6.80 and 13.64 as compared with normal weight participants. Model heritability estimates for bivariate variance due to an additive genetic component and non-shared environmental component were 75% (men) and 71% (women) for BMI, and 73% and 64%, respectively for type 2 diabetes. The correlations between genetic variance components (r g ) indicated that one fifth of the covariance of BMI and type 2 diabetes was due to shared genetic influences. Although the mean monozygotic concordance for type 2 diabetes was approximately twice the dizygotic one, age of onset of diabetes within twin pair members varied greatly, irrespective of zygosity. Conclusions/interpretation A 28-year follow-up of adult Finnish twins showed that despite high trait heritability estimates, only a fraction of covariation in BMI and incident type 2 diabetes was of genetic origin.

Leisure-time physical activity and type 2 diabetes during a 28 year follow-up in twins

“…The response rate was 89%. After excluding the participants with diagnosed diabetes at baseline, those of undefined zygosity and those who had moved abroad before 1976, the cohort consisted of 23,585 individuals with self-reported baseline data on education, social and occupational class, alcohol consumption, physical activity and BMI [19]. The final cohort for the present study included 20,487 individuals, with 8,182 complete twin pairs, who had complete physical activity information available for metabolic equivalent (MET) index calculations (see explanation below).…”

“…Diabetes assessment Type 2 diabetes information for 1976-1996 was collected from death certificates, the National Hospital Discharge Register and the Medication Register of the Social Insurance Institution by linking this information to the personal identification assigned to all residents of Finland [19]. The Social Insurance Institution of Finland (KELA) is the agency responsible for the provision of basic social security [19,29].…”

“…The Social Insurance Institution of Finland (KELA) is the agency responsible for the provision of basic social security [19,29]. KELA reimburses whole or part of the cost of necessary medications to patients who are certified by a physician as having a diagnosed severe chronic disease [30].…”

“…The date of onset of disease symptoms was determined and used in the analyses. The diabetes information for 1996-2004 was collected solely from the Medication Register and individuals were presumed to have type 2 diabetes, given their age [19]. For this period the date of being granted the right to reimbursable medication was used in the analysis as the date of disease onset.…”

“…Type 2 diabetes has been clearly shown to be an environmental disease, but it also has a genetic component [18], based on family, twin and genome-wide association studies [19]. Twin pairs nearly always share the same childhood family environment.…”