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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
- Gonneke Willemsen, Kirsten J. Ward, Christopher G. Bell, Kaare Christensen, Jocelyn Bowden, Christine Dalgård, Jennifer R. Harris, Jaakko Kaprio, Robert Lyle, Patrik K.E. Magnusson, Karen A. Mather, Juan R. Ordoňana, Francisco Perez-Riquelme, Nancy L. Pedersen, Kirsi H. Pietiläinen, Perminder S. Sachdev, Dorret I. Boomsma, Tim Spector
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- Journal:
- Twin Research and Human Genetics / Volume 18 / Issue 6 / December 2015
- Published online by Cambridge University Press:
- 18 December 2015, pp. 762-771
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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.
Zygosity Differences in Height and Body Mass Index of Twins From Infancy to Old Age: A Study of the CODATwins Project
- Aline Jelenkovic, Yoshie Yokoyama, Reijo Sund, Chika Honda, Leonie H Bogl, Sari Aaltonen, Fuling Ji, Feng Ning, Zengchang Pang, Juan R. Ordoñana, Juan F. Sánchez-Romera, Lucia Colodro-Conde, S. Alexandra Burt, Kelly L. Klump, Sarah E. Medland, Grant W. Montgomery, Christian Kandler, Tom A. McAdams, Thalia C. Eley, Alice M. Gregory, Kimberly J. Saudino, Lise Dubois, Michel Boivin, Adam D. Tarnoki, David L. Tarnoki, Claire M. A. Haworth, Robert Plomin, Sevgi Y. Öncel, Fazil Aliev, Maria A. Stazi, Corrado Fagnani, Cristina D’Ippolito, Jeffrey M. Craig, Richard Saffery, Sisira H. Siribaddana, Matthew Hotopf, Athula Sumathipala, Fruhling Rijsdijk, Timothy Spector, Massimo Mangino, Genevieve Lachance, Margaret Gatz, David A. Butler, Gombojav Bayasgalan, Danshiitsoodol Narandalai, Duarte L Freitas, José Antonio Maia, K. Paige Harden, Elliot M. Tucker-Drob, Bia Kim, Youngsook Chong, Changhee Hong, Hyun Jung Shin, Kaare Christensen, Axel Skytthe, Kirsten O. Kyvik, Catherine A. Derom, Robert F. Vlietinck, Ruth J. F. Loos, Wendy Cozen, Amie E. Hwang, Thomas M. Mack, Mingguang He, Xiaohu Ding, Billy Chang, Judy L. Silberg, Lindon J. Eaves, Hermine H. Maes, Tessa L. Cutler, John L. Hopper, Kelly Aujard, Patrik K. E. Magnusson, Nancy L. Pedersen, Anna K. Dahl Aslan, Yun-Mi Song, Sarah Yang, Kayoung Lee, Laura A. Baker, Catherine Tuvblad, Morten Bjerregaard-Andersen, Henning Beck-Nielsen, Morten Sodemann, Kauko Heikkilä, Qihua Tan, Dongfeng Zhang, Gary E. Swan, Ruth Krasnow, Kerry L. Jang, Ariel Knafo-Noam, David Mankuta, Lior Abramson, Paul Lichtenstein, Robert F. Krueger, Matt McGue, Shandell Pahlen, Per Tynelius, Glen E. Duncan, Dedra Buchwald, Robin P. Corley, Brooke M. Huibregtse, Tracy L. Nelson, Keith E. Whitfield, Carol E. Franz, William S. Kremen, Michael J. Lyons, Syuichi Ooki, Ingunn Brandt, Thomas Sevenius Nilsen, Fujio Inui, Mikio Watanabe, Meike Bartels, Toos C. E. M. van Beijsterveldt, Jane Wardle, Clare H. Llewellyn, Abigail Fisher, Esther Rebato, Nicholas G. Martin, Yoshinori Iwatani, Kazuo Hayakawa, Joohon Sung, Jennifer R. Harris, Gonneke Willemsen, Andreas Busjahn, Jack H. Goldberg, Finn Rasmussen, Yoon-Mi Hur, Dorret I. Boomsma, Thorkild I. A. Sørensen, Jaakko Kaprio, Karri Silventoinen
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- Journal:
- Twin Research and Human Genetics / Volume 18 / Issue 5 / October 2015
- Published online by Cambridge University Press:
- 04 September 2015, pp. 557-570
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A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
In the Endemic Setting, Clostridium difficile Ribotype 027 Is Virulent But Not Hypervirulent
- Samuel L. Aitken, M. Jahangir Alam, Mohammed Khaleduzzuman, Seth T. Walk, William L. Musick, Vy P. Pham, Jennifer L. Christensen, Robert L. Atmar, Yang Xie, Kevin W. Garey
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- Journal:
- Infection Control & Hospital Epidemiology / Volume 36 / Issue 11 / November 2015
- Published online by Cambridge University Press:
- 20 August 2015, pp. 1318-1323
- Print publication:
- November 2015
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BACKGROUND
Conflicting reports have been published on the association between Clostridium difficile ribotypes and severe disease outcomes in patients with C. difficile infection (CDI); several so-called hypervirulent ribotypes have been described. We performed a multicenter study to assess severe disease presentation and severe outcomes among CDI patients infected with different ribotypes.
METHODSStool samples that tested positive for C. difficile toxin were collected and cultured from patients who presented to any of 7 different hospitals in Houston, Texas (2011–2013). C. difficile was characterized using a fluorescent PCR ribotyping method. Medical records were reviewed to determine clinical characteristics and ribotype association with severe CDI presentation (ie, leukocytosis and/or hypoalbuminemia) and severe CDI outcomes (ie, ICU admission, ileus, toxic megacolon, colectomy, and/or in-hospital death).
RESULTSOur study included 715 patients aged 61±18 years (female: 63%; median Charlson comorbidity index: 2.5±2.4; hospital-onset CDI: 45%; severe CDI: 36.7%; severe CDI outcomes: 12.3%). The most common ribotypes were 027, 014-020, FP311, 002, 078-126, and 001. Ribotype 027 was a significant independent predictor of severe disease (adjusted odds ratio [aOR], 2.24; 95% confidence interval [CI], 1.53–3.29; P<.001) and severe CDI outcomes (aOR, 1.71; 95% CI, 1.02–2.85; P=.041) compared with all other ribotypes in aggregate. However, in an analysis using all common ribotypes as individual variables, ribotype 027 was not associated with severe CDI outcomes more often than other ribotypes.
CONCLUSIONRibotype 027 showed virulence equal to that of other ribotypes identified in this endemic setting. Clinical severity markers of CDI may be more predictive of severe CDI outcomes than a particular ribotype.
Infect. Control Hosp. Epidemiol. 2015;36(11):1318–1323
The CODATwins Project: The Cohort Description of Collaborative Project of Development of Anthropometrical Measures in Twins to Study Macro-Environmental Variation in Genetic and Environmental Effects on Anthropometric Traits
- Karri Silventoinen, Aline Jelenkovic, Reijo Sund, Chika Honda, Sari Aaltonen, Yoshie Yokoyama, Adam D. Tarnoki, David L. Tarnoki, Feng Ning, Fuling Ji, Zengchang Pang, Juan R. Ordoñana, Juan F. Sánchez-Romera, Lucia Colodro-Conde, S. Alexandra Burt, Kelly L. Klump, Sarah E. Medland, Grant W. Montgomery, Christian Kandler, Tom A. McAdams, Thalia C. Eley, Alice M. Gregory, Kimberly J. Saudino, Lise Dubois, Michel Boivin, Claire M. A. Haworth, Robert Plomin, Sevgi Y. Öncel, Fazil Aliev, Maria A. Stazi, Corrado Fagnani, Cristina D’Ippolito, Jeffrey M. Craig, Richard Saffery, Sisira H. Siribaddana, Matthew Hotopf, Athula Sumathipala, Timothy Spector, Massimo Mangino, Genevieve Lachance, Margaret Gatz, David A. Butler, Gombojav Bayasgalan, Danshiitsoodol Narandalai, Duarte L. Freitas, José Antonio Maia, K. Paige Harden, Elliot M. Tucker-Drob, Kaare Christensen, Axel Skytthe, Kirsten O. Kyvik, Changhee Hong, Youngsook Chong, Catherine A. Derom, Robert F. Vlietinck, Ruth J. F. Loos, Wendy Cozen, Amie E. Hwang, Thomas M. Mack, Mingguang He, Xiaohu Ding, Billy Chang, Judy L. Silberg, Lindon J. Eaves, Hermine H. Maes, Tessa L. Cutler, John L. Hopper, Kelly Aujard, Patrik K. E. Magnusson, Nancy L. Pedersen, Anna K. Dahl Aslan, Yun-Mi Song, Sarah Yang, Kayoung Lee, Laura A. Baker, Catherine Tuvblad, Morten Bjerregaard-Andersen, Henning Beck-Nielsen, Morten Sodemann, Kauko Heikkilä, Qihua Tan, Dongfeng Zhang, Gary E. Swan, Ruth Krasnow, Kerry L. Jang, Ariel Knafo-Noam, David Mankuta, Lior Abramson, Paul Lichtenstein, Robert F. Krueger, Matt McGue, Shandell Pahlen, Per Tynelius, Glen E. Duncan, Dedra Buchwald, Robin P. Corley, Brooke M. Huibregtse, Tracy L. Nelson, Keith E. Whitfield, Carol E. Franz, William S. Kremen, Michael J. Lyons, Syuichi Ooki, Ingunn Brandt, Thomas Sevenius Nilsen, Fujio Inui, Mikio Watanabe, Meike Bartels, Toos C. E. M. van Beijsterveldt, Jane Wardle, Clare H. Llewellyn, Abigail Fisher, Esther Rebato, Nicholas G. Martin, Yoshinori Iwatani, Kazuo Hayakawa, Finn Rasmussen, Joohon Sung, Jennifer R. Harris, Gonneke Willemsen, Andreas Busjahn, Jack H. Goldberg, Dorret I. Boomsma, Yoon-Mi Hur, Thorkild I. A. Sørensen, Jaakko Kaprio
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- Journal:
- Twin Research and Human Genetics / Volume 18 / Issue 4 / August 2015
- Published online by Cambridge University Press:
- 27 May 2015, pp. 348-360
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For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
Genetic Factors in Seizures: A Population-Based Study of 47,626 US, Norwegian and Danish Twin Pairs
- Marianne J. Kjeldsen, Linda A. Corey, Marit H. Solaas, Mogens L. Friis, Jennifer R. Harris, Kirsten O. Kyvik, Kaare Christensen, John M. Pellock
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- Journal:
- Twin Research and Human Genetics / Volume 8 / Issue 2 / 01 April 2005
- Published online by Cambridge University Press:
- 21 February 2012, pp. 138-147
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The purpose of the study was to describe a large sample of twins reporting a history of seizures, to characterize seizures in the three subpopulations, and to estimate the relative importance of genetic and environmental factors in seizure occurrence. Seizure history was determined by questionnaires completed by twins in population-based twin registries in the United States, Norway and Denmark. Concordance rates were calculated for all seizure categories within and across twin populations. Of 47,626 twin pairs evaluated, 6234 reported a history of seizures in one or both twins. Concordance rates were significantly higher for monozygotic (MZ) versus dizygotic (DZ) pairs for all seizure categories within and across populations. The results of this study involving the largest unselected, population-based sample of twins with seizures assembled to date confirm the importance of genetic factors in determining risk for epilepsy, febrile seizures, other seizures and staring spells. This sample is likely to provide an important resource for studying the genetics of epilepsy subtypes and febrile seizures.
Contributors
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- By Isabella Aboderin, W. Andrew Achenbaum, Katherine R. Allen, Toni C. Antonucci, Sara Arber, Claudine Attias‐Donfut, Paul B. Baltes, Sandhi Maria Barreto, Vern L. Bengtson, Simon Biggs, Joanna Bornat, Julie B. Boron, Mike Boulton, Clive E. Bowman, Marjolein Broese van Groenou, Edna Brown, Robert N. Butler, Bill Bytheway, Neena L. Chappell, Neil Charness, Kaare Christensen, Peter G. Coleman, Ingrid Arnet Connidis, Neal E. Cutler, Sara J. Czaja, Svein Olav Daatland, Lia Susana Daichman, Adam Davey, Bleddyn Davies, Freya Dittmann‐Kohli, Glen H. Elder, Carroll L. Estes, Mike Featherstone, Amy Fiske, Alexandra Freund, Daphna Gans, Linda K. George, Roseann Giarrusso, Chris Gilleard, Jay Ginn, Edlira Gjonça, Elena L. Grigorenko, Jaber F. Gubrium, Sarah Harper, Jutta Heckhausen, Akiko Hashimoto, Jon Hendricks, Mike Hepworth, Charlotte Ikels, James S. Jackson, Yuri Jang, Bernard Jeune, Malcolm L. Johnson, Randi S. Jones, Alexandre Kalache, Robert L. Kane, Rosalie A. Kane, Ingrid Keller, Rose Anne Kenny, Thomas B. L. Kirkwood, Kees Knipscheer, Martin Kohli, Gisela Labouvie‐Vief, Kristina Larsson, Shu‐Chen Li, Charles F. Longino, Ariela Lowenstein, Erick McCarthy, Gerald E. McClearn, Brendan McCormack, Elizabeth MacKinlay, Alfons Marcoen, Michael Marmot, Tom Margrain, Victor W. Marshall, Elizabeth A. Maylor, Ruud ter Meulen, Harry R. Moody, Robert A. Neimeyer, Demi Patsios, Margaret J. Penning, Stephen A. Petrill, Chris Phillipson, Leonard W. Poon, Norella M. Putney, Jill Quadagno, Pat Rabbitt, Jennifer Reid Keene, Sandra G. Reynolds, Steven R. Sabat, Clive Seale, Merril Silverstein, Hannes B. Staehelin, Ursula M. Staudinger, Robert J. Sternberg, Debra Street, Philip Taylor, Fleur Thomése, Mats Thorslund, Jinzhou Tian, Theo van Tilburg, Fernando M. Torres‐Gil, Josy Ubachs‐Moust, Christina Victor, K. Warner Shaie, Anthony M. Warnes, James L. Werth, Sherry L. Willis, François‐Charles Wolff, Bob Woods
- Edited by Malcolm L. Johnson, University of Bristol
- Edited in association with Vern L. Bengtson, University of Southern California, Peter G. Coleman, University of Southampton, Thomas B. L. Kirkwood, University of Newcastle upon Tyne
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- Book:
- The Cambridge Handbook of Age and Ageing
- Published online:
- 05 June 2016
- Print publication:
- 01 December 2005, pp xii-xvi
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