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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

Lehtovirta, M.; Pietilainen, K. H.; Levalahti, E.; Heikkila, K.; Groop, Leif LU ; Silventoinen, K.; Koskenvuo, M. and Kaprio, J. (2010) In Diabetologia 53(7). p.1314-1321
Abstract
We investigated whether BMI predicts type 2 diabetes in twins and to what extent that is explained by common genetic factors. This was a population-based twin cohort study. Monozygotic (n = 4,076) and dizygotic (n = 9,109) non-diabetic 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. 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... (More)
We investigated whether BMI predicts type 2 diabetes in twins and to what extent that is explained by common genetic factors. This was a population-based twin cohort study. Monozygotic (n = 4,076) and dizygotic (n = 9,109) non-diabetic 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. 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. 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Proportional hazards models, Body mass index, Follow-up studies, Twins, Type 2 diabetes mellitus
in
Diabetologia
volume
53
issue
7
pages
1314 - 1321
publisher
Springer Verlag
external identifiers
  • wos:000278118700009
  • scopus:77955665767
ISSN
1432-0428
DOI
10.1007/s00125-010-1746-4
language
English
LU publication?
yes
id
93d8b2df-11ec-4223-80f0-1fe1112379ed (old id 1616825)
date added to LUP
2010-06-22 13:19:38
date last changed
2018-05-29 09:20:53
@article{93d8b2df-11ec-4223-80f0-1fe1112379ed,
  abstract     = {We investigated whether BMI predicts type 2 diabetes in twins and to what extent that is explained by common genetic factors. This was a population-based twin cohort study. Monozygotic (n = 4,076) and dizygotic (n = 9,109) non-diabetic 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. 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. 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.},
  author       = {Lehtovirta, M. and Pietilainen, K. H. and Levalahti, E. and Heikkila, K. and Groop, Leif and Silventoinen, K. and Koskenvuo, M. and Kaprio, J.},
  issn         = {1432-0428},
  keyword      = {Proportional hazards models,Body mass index,Follow-up studies,Twins,Type 2 diabetes mellitus},
  language     = {eng},
  number       = {7},
  pages        = {1314--1321},
  publisher    = {Springer Verlag},
  series       = {Diabetologia},
  title        = {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},
  url          = {http://dx.doi.org/10.1007/s00125-010-1746-4},
  volume       = {53},
  year         = {2010},
}