BACKGROUND: The contribution of hereditary and environmental factors to the development of abdominal aortic aneurysms (AAAs) is still partly unknown. The aim of this study was to analyze the role of these factors in a large population-based sample of twins. METHODS: The Swedish Twin Registry, containing data on twins born in the country since 1886, was cross-linked with the Inpatient Registry, providing national coverage of discharge diagnoses coded according to the International Classification of Diseases (ICD). All twins with an infrarenal AAA were identified. Concordance rates and tetrachoric correlations were calculated for monozygotic (MZ) and dizygotic (DZ) twins. Tetrachoric correlations were calculated assuming an underlying normal distribution of liability, with multiple factors contributing additively and a threshold value that discriminates between AAA and no AAA. Higher concordance rates and correlations of liability in MZ twins than in DZ twins suggest that genetic factors influence disease development. Structural equation modeling techniques, Mx-analyses, were used to estimate the contributions of genetic effects as well as shared and nonshared environmental factors for development of AAA. RESULTS: There were 172,890 twins registered at the time of the study including 265 twins (81% men; mean age 72 years; range, 48-94) with AAA. There were 7 MZ and 5 DZ concordant pairs as well as 44 MZ and 197 DZ discordant pairs with AAA. The probandwise concordance rates for MZ and DZ pairs were 24% and 4.8%, respectively. The tetrachoric correlations were 0.71 in MZ pairs and 0.31 in DZ pairs. The odds ratio (OR) was 71 (95% confidence interval [CI] 27-183) for MZ twins and 7.6 (95% CI 3.0-19) for DZ twins. In the structural equation models, genetic effects accounted for 70% (95% CI 0.33-0.83), shared environmental effects for 0% (95% CI 0-0.27), and nonshared environmental effects for 30% (95% CI 0.17-0.46) of the phenotypic variance among twins. CONCLUSION: These data provide robust epidemiologic evidence that heritability contributes to aneurysm formation. Concordances and correlations were higher in MZ compared with DZ twins, indicating genetic effects. There was a 24% probability that an MZ twin of a person with AAA will have the disease. The twin of an MZ twin with AAA had a risk of AAA that was 71 times that of the MZ twin of a person without AAA. A heritability of 70% of the total trait variance was estimated. The remaining variance was explained by nonshared environmental factors with no support for a role of shared environmental influences. Copyright 2010 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.
BACKGROUND: The contribution of hereditary and environmental factors to the development of abdominal aortic aneurysms (AAAs) is still partly unknown. The aim of this study was to analyze the role of these factors in a large population-based sample of twins. METHODS: The Swedish Twin Registry, containing data on twins born in the country since 1886, was cross-linked with the Inpatient Registry, providing national coverage of discharge diagnoses coded according to the International Classification of Diseases (ICD). All twins with an infrarenal AAA were identified. Concordance rates and tetrachoric correlations were calculated for monozygotic (MZ) and dizygotic (DZ) twins. Tetrachoric correlations were calculated assuming an underlying normal distribution of liability, with multiple factors contributing additively and a threshold value that discriminates between AAA and no AAA. Higher concordance rates and correlations of liability in MZ twins than in DZ twins suggest that genetic factors influence disease development. Structural equation modeling techniques, Mx-analyses, were used to estimate the contributions of genetic effects as well as shared and nonshared environmental factors for development of AAA. RESULTS: There were 172,890 twins registered at the time of the study including 265 twins (81% men; mean age 72 years; range, 48-94) with AAA. There were 7 MZ and 5 DZ concordant pairs as well as 44 MZ and 197 DZ discordant pairs with AAA. The probandwise concordance rates for MZ and DZ pairs were 24% and 4.8%, respectively. The tetrachoric correlations were 0.71 in MZ pairs and 0.31 in DZ pairs. The odds ratio (OR) was 71 (95% confidence interval [CI] 27-183) for MZ twins and 7.6 (95% CI 3.0-19) for DZ twins. In the structural equation models, genetic effects accounted for 70% (95% CI 0.33-0.83), shared environmental effects for 0% (95% CI 0-0.27), and nonshared environmental effects for 30% (95% CI 0.17-0.46) of the phenotypic variance among twins. CONCLUSION: These data provide robust epidemiologic evidence that heritability contributes to aneurysm formation. Concordances and correlations were higher in MZ compared with DZ twins, indicating genetic effects. There was a 24% probability that an MZ twin of a person with AAA will have the disease. The twin of an MZ twin with AAA had a risk of AAA that was 71 times that of the MZ twin of a person without AAA. A heritability of 70% of the total trait variance was estimated. The remaining variance was explained by nonshared environmental factors with no support for a role of shared environmental influences. Copyright 2010 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.
Authors: Helena Kuivaniemi; Natzi Sakalihasan; Frank A Lederle; Gregory T Jones; Jean-Olivier Defraigne; Nicos Labropoulos; Victor Legrand; Jean-Baptiste Michel; Christoph Nienaber; Marc A Radermecker; John A Elefteriades Journal: Aorta (Stamford) Date: 2013-06-01
Authors: Solveig Gretarsdottir; Annette F Baas; Gudmar Thorleifsson; Hilma Holm; Martin den Heijer; Jean-Paul P M de Vries; Steef E Kranendonk; Clark J A M Zeebregts; Steven M van Sterkenburg; Robert H Geelkerken; Andre M van Rij; Michael J A Williams; Albert P M Boll; Jelena P Kostic; Adalbjorg Jonasdottir; Aslaug Jonasdottir; G Bragi Walters; Gisli Masson; Patrick Sulem; Jona Saemundsdottir; Magali Mouy; Kristinn P Magnusson; Gerard Tromp; James R Elmore; Natzi Sakalihasan; Raymond Limet; Jean-Olivier Defraigne; Robert E Ferrell; Antti Ronkainen; Ynte M Ruigrok; Cisca Wijmenga; Diederick E Grobbee; Svati H Shah; Christopher B Granger; Arshed A Quyyumi; Viola Vaccarino; Riyaz S Patel; A Maziar Zafari; Allan I Levey; Harland Austin; Domenico Girelli; Pier Franco Pignatti; Oliviero Olivieri; Nicola Martinelli; Giovanni Malerba; Elisabetta Trabetti; Lewis C Becker; Diane M Becker; Muredach P Reilly; Daniel J Rader; Thomas Mueller; Benjamin Dieplinger; Meinhard Haltmayer; Sigitas Urbonavicius; Bengt Lindblad; Anders Gottsäter; Eleonora Gaetani; Roberto Pola; Philip Wells; Marc Rodger; Melissa Forgie; Nicole Langlois; Javier Corral; Vicente Vicente; Jordi Fontcuberta; Francisco España; Niels Grarup; Torben Jørgensen; Daniel R Witte; Torben Hansen; Oluf Pedersen; Katja K Aben; Jacqueline de Graaf; Suzanne Holewijn; Lasse Folkersen; Anders Franco-Cereceda; Per Eriksson; David A Collier; Hreinn Stefansson; Valgerdur Steinthorsdottir; Thorunn Rafnar; Einar M Valdimarsson; Hulda B Magnadottir; Sigurlaug Sveinbjornsdottir; Isleifur Olafsson; Magnus Karl Magnusson; Robert Palmason; Vilhelmina Haraldsdottir; Karl Andersen; Pall T Onundarson; Gudmundur Thorgeirsson; Lambertus A Kiemeney; Janet T Powell; David J Carey; Helena Kuivaniemi; Jes S Lindholt; Gregory T Jones; Augustine Kong; Jan D Blankensteijn; Stefan E Matthiasson; Unnur Thorsteinsdottir; Kari Stefansson Journal: Nat Genet Date: 2010-07-11 Impact factor: 38.330
Authors: Weihong Tang; Athanasios Saratzis; Jack Pattee; Jacqueline Smith; Nathan Pankratz; Olivia C Leavy; Weihua Guan; Frank Dudbridge; James S Pankow; George D Kitas; Pamela L Lutsey; Matthew J Bown Journal: Eur J Vasc Endovasc Surg Date: 2019-11-01 Impact factor: 7.069