Editor's Choice - High Heritability of Liability to Abdominal Aortic Aneurysms: A Population Based Twin Study.

OBJECTIVE: First degree relatives of patients with abdominal aortic aneurysm (AAA) have an increased risk of developing AAA; however, despite intensive investigation, the specific genetic factors involved in the development of the disease are still largely unknown. 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 objective of this study was to investigate the heritability of AAA among Danish twins using concordance rates and heritability estimates. METHODS: The Danish Twin Registry was used to identify all Danish twin pairs (born 1880-1971) where both twins were alive on January 1, 1977. AAA cases were then identified using the National Patient Registry and the Registry of Cause of Death. Probandwise concordance rates were calculated and heritability estimated using structural equation modeling. RESULTS: The study identified 414 twins with AAA; 69.8% (289/414) were men and 30.2% (125/414) women. The probandwise concordance rate in MZ twins was 30% (95% CI 20.3-43.3%) compared with 12% (95% CI 7.0-20.1%) in DZ twins. In the heritability analysis 77% (95% CI 67-85%) of the total variance was explained by additive genetic components and 23% (95% CI 15-33%) was explained by non-shared environmental factors. CONCLUSIONS: The probandwise concordance rate was found to be 2.5 times higher in MZ compared with DZ twins. An overall heritability of 77% was determined.

Abdominal aortic diameter is increased in males with a family history of abdominal aortic aneurysms: results from the Danish VIVA-trial.

OBJECTIVE: To investigate, at a population level, whether a family history of abdominal aortic aneurysm (AAA) is independently related to increased aortic diameter and prevalence of AAA in men, and to elucidate whether the mean aortic diameter and the prevalence of AAA are different between participants with male and female relatives with AAA. DESIGN: Observational population-based cross-sectional study. MATERIALS: 18,614 male participants screened for AAA in the VIVA-trial 2008-2011 with information on both family history of AAA and maximal aortic diameter. METHODS: Standardized ultrasound scan measurement of maximum antero-posterior aortic diameter. Family history obtained by questionnaire. Multivariate regression analysis was used to test for confounders: age, sex, smoking, comorbidity and medication. RESULTS: From the screened cohort, 569 participants had at least one first degree relative diagnosed with AAA, and 38 had AAA. Participants with a family history of AAA (+FH) had a significantly larger mean maximum aortic diameter (20.50 mm) compared with participants without family history of AAA (-FH) (19.07 mm, p < .0001), and +FH with female relatives with AAA had significantly larger mean maximum aortic diameter (21.8 mm) than +FH with male relatives (19.9 mm, p = .007). Furthermore the prevalence of AAA was significantly higher among +FH (6.7%) compared with -FH (3.0%) with an odds ratio (OR) of 2.2 (95% CI: 1.6 to 3.2, p < .001) and +FH with female relatives with AAA had a more than two and a half times increased prevalence of AAA compared with +FH with male relatives with AAA with an OR of 2.65. CONCLUSIONS: First-degree male relatives of AAA patients have wider aortas and a twofold higher prevalence of AAA compared with the age adjusted background population. The prevalence of AAA was markedly higher in participants related to female, rather than male, patients with AAA.