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Genetic and environmental contributions to abdominal aortic aneurysm development in a twin population.
J Vasc Surg 2010; 51(1):3-7; discussion 7JV

Abstract

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.

Authors+Show Affiliations

Department of Vascular Surgery, Karolinska University Hospital, Stockholm, Sweden. carl.wahlgren@karolinska.seNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Twin Study

Language

eng

PubMed ID

19939604

Citation

Wahlgren, Carl Magnus, et al. "Genetic and Environmental Contributions to Abdominal Aortic Aneurysm Development in a Twin Population." Journal of Vascular Surgery, vol. 51, no. 1, 2010, pp. 3-7; discussion 7.
Wahlgren CM, Larsson E, Magnusson PK, et al. Genetic and environmental contributions to abdominal aortic aneurysm development in a twin population. J Vasc Surg. 2010;51(1):3-7; discussion 7.
Wahlgren, C. M., Larsson, E., Magnusson, P. K., Hultgren, R., & Swedenborg, J. (2010). Genetic and environmental contributions to abdominal aortic aneurysm development in a twin population. Journal of Vascular Surgery, 51(1), pp. 3-7; discussion 7. doi:10.1016/j.jvs.2009.08.036.
Wahlgren CM, et al. Genetic and Environmental Contributions to Abdominal Aortic Aneurysm Development in a Twin Population. J Vasc Surg. 2010;51(1):3-7; discussion 7. PubMed PMID: 19939604.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetic and environmental contributions to abdominal aortic aneurysm development in a twin population. AU - Wahlgren,Carl Magnus, AU - Larsson,Emma, AU - Magnusson,Patrik K E, AU - Hultgren,Rebecka, AU - Swedenborg,Jesper, Y1 - 2009/11/24/ PY - 2009/06/02/received PY - 2009/08/05/revised PY - 2009/08/15/accepted PY - 2009/11/27/entrez PY - 2009/11/27/pubmed PY - 2010/2/24/medline SP - 3-7; discussion 7 JF - Journal of vascular surgery JO - J. Vasc. Surg. VL - 51 IS - 1 N2 - 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. SN - 1097-6809 UR - https://www.unboundmedicine.com/medline/citation/19939604/Genetic_and_environmental_contributions_to_abdominal_aortic_aneurysm_development_in_a_twin_population_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0741-5214(09)01678-4 DB - PRIME DP - Unbound Medicine ER -