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The concordance and heritability of Type 2 Diabetes in 34,166 twin pairs from international twin registers: The Discordant Twin (DISCOTWIN) Consortium.

The concordance and heritability of Type 2 Diabetes in 34,166 twin pairs from international twin registers: The Discordant Twin (DISCOTWIN) Consortium.
The concordance and heritability of Type 2 Diabetes in 34,166 twin pairs from international twin registers: The Discordant Twin (DISCOTWIN) Consortium.
Twin pairs discordant for disease may help elucidate the epigenetic mechanisms and causal environmental factors in disease development and progression. To obtain the numbers of pairs, especially monozygotic (MZ) twin pairs, necessary for in-depth studies while also allowing for replication, twin studies worldwide need to pool their resources. The Discordant Twin (DISCOTWIN) consortium was established for this goal. Here, we describe the DISCOTWIN Consortium and present an analysis of type 2 diabetes (T2D) data in nearly 35,000 twin pairs. Seven twin cohorts from Europe (Denmark, Finland, Norway, the Netherlands, Spain, Sweden, and the United Kingdom) and one from Australia investigated the rate of discordance for T2D in same-sex twin pairs aged 45 years and older. Data were available for 34,166 same-sex twin pairs, of which 13,970 were MZ, with T2D diagnosis based on self-reported diagnosis and medication use, fasting glucose and insulin measures, or medical records. The prevalence of T2D ranged from 2.6% to 12.3% across the cohorts depending on age, body mass index (BMI), and national diabetes prevalence. T2D discordance rate was lower for MZ (5.1%, range 2.9-11.2%) than for same-sex dizygotic (DZ) (8.0%, range 4.9-13.5%) pairs. Across DISCOTWIN, 720 discordant MZ pairs were identified. Except for the oldest of the Danish cohorts (mean age 79), heritability estimates based on contingency tables were moderate to high (0.47-0.77). From a meta-analysis of all data, the heritability was estimated at 72% (95% confidence interval 61-78%). This study demonstrated high T2D prevalence and high heritability for T2D liability across twin cohorts. Therefore, the number of discordant MZ pairs for T2D is limited. By combining national resources, the DISCOTWIN Consortium maximizes the number of discordant MZ pairs needed for in-depth genotyping, multi-omics, and phenotyping studies, which may provide unique insights into the pathways linking genes to the development of many diseases.
1832-4274
762-771
Willemsen, Gonneke
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Ward, Kirsten J.
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Bell, Christopher G.
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Christensen, Kaare
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Bowden, Jocelyn
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Dalgård, Christine
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Harris, Jennifer R.
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Kaprio, Jaakko
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Lyle, Robert
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Magnusson, Patrik K.E.
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Mather, Karen A.
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Ordoňana, Juan R.
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Perez-Riquelme, Francisco
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Pedersen, Nancy L.
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Pietiläinen, Kirsi H.
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Sachdev, Perminder S.
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Boomsma, Dorret I.
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Spector, Tim
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Willemsen, Gonneke
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Ward, Kirsten J.
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Bell, Christopher G.
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Christensen, Kaare
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Bowden, Jocelyn
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Dalgård, Christine
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Harris, Jennifer R.
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Kaprio, Jaakko
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Lyle, Robert
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Magnusson, Patrik K.E.
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Mather, Karen A.
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Ordoňana, Juan R.
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Perez-Riquelme, Francisco
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Pedersen, Nancy L.
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Pietiläinen, Kirsi H.
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Sachdev, Perminder S.
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Boomsma, Dorret I.
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Spector, Tim
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Willemsen, Gonneke, Ward, Kirsten J., Bell, Christopher G., Christensen, Kaare, Bowden, Jocelyn, Dalgård, Christine, Harris, Jennifer R., Kaprio, Jaakko, Lyle, Robert, Magnusson, Patrik K.E., Mather, Karen A., Ordoňana, Juan R., Perez-Riquelme, Francisco, Pedersen, Nancy L., Pietiläinen, Kirsi H., Sachdev, Perminder S., Boomsma, Dorret I. and Spector, Tim (2015) The concordance and heritability of Type 2 Diabetes in 34,166 twin pairs from international twin registers: The Discordant Twin (DISCOTWIN) Consortium. Twin Research and Human Genetics, 18 (6), 762-771. (doi:10.1017/thg.2015.83). (PMID:26678054)

Record type: Article

Abstract

Twin pairs discordant for disease may help elucidate the epigenetic mechanisms and causal environmental factors in disease development and progression. To obtain the numbers of pairs, especially monozygotic (MZ) twin pairs, necessary for in-depth studies while also allowing for replication, twin studies worldwide need to pool their resources. The Discordant Twin (DISCOTWIN) consortium was established for this goal. Here, we describe the DISCOTWIN Consortium and present an analysis of type 2 diabetes (T2D) data in nearly 35,000 twin pairs. Seven twin cohorts from Europe (Denmark, Finland, Norway, the Netherlands, Spain, Sweden, and the United Kingdom) and one from Australia investigated the rate of discordance for T2D in same-sex twin pairs aged 45 years and older. Data were available for 34,166 same-sex twin pairs, of which 13,970 were MZ, with T2D diagnosis based on self-reported diagnosis and medication use, fasting glucose and insulin measures, or medical records. The prevalence of T2D ranged from 2.6% to 12.3% across the cohorts depending on age, body mass index (BMI), and national diabetes prevalence. T2D discordance rate was lower for MZ (5.1%, range 2.9-11.2%) than for same-sex dizygotic (DZ) (8.0%, range 4.9-13.5%) pairs. Across DISCOTWIN, 720 discordant MZ pairs were identified. Except for the oldest of the Danish cohorts (mean age 79), heritability estimates based on contingency tables were moderate to high (0.47-0.77). From a meta-analysis of all data, the heritability was estimated at 72% (95% confidence interval 61-78%). This study demonstrated high T2D prevalence and high heritability for T2D liability across twin cohorts. Therefore, the number of discordant MZ pairs for T2D is limited. By combining national resources, the DISCOTWIN Consortium maximizes the number of discordant MZ pairs needed for in-depth genotyping, multi-omics, and phenotyping studies, which may provide unique insights into the pathways linking genes to the development of many diseases.

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e-pub ahead of print date: 18 December 2015
Published date: December 2015
Organisations: Human Development & Health, Centre for Biological Sciences, MRC Life-Course Epidemiology Unit

Identifiers

Local EPrints ID: 400980
URI: http://eprints.soton.ac.uk/id/eprint/400980
ISSN: 1832-4274
PURE UUID: 1b80ddef-6aaa-40de-81d6-b1fae2845fb3
ORCID for Christopher G. Bell: ORCID iD orcid.org/0000-0003-4601-1242

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Date deposited: 03 Oct 2016 09:00
Last modified: 15 Mar 2024 02:35

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Contributors

Author: Gonneke Willemsen
Author: Kirsten J. Ward
Author: Christopher G. Bell ORCID iD
Author: Kaare Christensen
Author: Jocelyn Bowden
Author: Christine Dalgård
Author: Jennifer R. Harris
Author: Jaakko Kaprio
Author: Robert Lyle
Author: Patrik K.E. Magnusson
Author: Karen A. Mather
Author: Juan R. Ordoňana
Author: Francisco Perez-Riquelme
Author: Nancy L. Pedersen
Author: Kirsi H. Pietiläinen
Author: Perminder S. Sachdev
Author: Dorret I. Boomsma
Author: Tim Spector

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