High Heritability of Abdominal Aortic Aneurysms – A Population-based Twin-study

Abstract

Introduction: It is well known that there is an increased risk of developing abdominal aneurysms (AAA) among first-degree relatives of AAA-patients; however, it is still uncertain how great a role genetics generally play in the development of the disease. In twin studies the influence of genetic and environmental factors can be assessed by comparing concordance rates between monozygotic (MZ) and dizygotic (DZ) twins. Higher phenotypic similarity between MZ than DZ twins indicates a genetic attribution to the etiology. The primary aim of this study was to investigate the heritability of AAA among Danish twins using concordance rates and heritability estimates. Secondary aims were to investigate possible differences between gender regarding age at diagnosis and prevalence. Methods: We identified all Danish twins with AAA using three different population-based registries: the National Hospital Patient Registry, the Registry of Cause of Death and the Danish Twin Registry, which were linked together using the Danish Civil Registration System. We calculated age at diagnosis and prevalence for both men and women, and proband-wise concordance rates. Heritability was estimated using tetrachoric correlations and structural ADCE-modelling. Results: We included 65 –820 twins (32 –910 pairs). We identified 414 twins with AAA; 69.8 % (289/414) were men and 30.2 % (125/414) women. Mean age at diagnosis was 69.7 years with no significant difference between men and women (69.6 vs. 70.0 years, p = 0.64). The prevalence across all zygosities was 0.87% in men and 0.39% in women. The proband-wise concordance rate in MZ twins was 30.6% (95% CI (confidence interval):20.3;43.3%) compared with 12.2% (95%CI:7.0;20.1%) in DZ twins. In the analysis of heritability 77% (95%CI:67;85%) of the total variance could be explained by additive genetic components. The rest of the variance could be explained by non-shared environmental factors, whereas genetic dominance and shared environmental factors were not needed to account for the observed variance. Conclusion: In this study we found more than a two times higher concordance rate in MZ twins compared with DZ twins, which indicates a genetic component in the development of AAA. Furthermore we found an overall heritability of 77 % meaning genetic variance accounts for more than ¾ of the total phenotypic variance. Prevalences were generally low with women accounting for about a third of the AAA-cases and we found no difference between genders regarding age at diagnosis.