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2004: Shibamura Hidenori; Olson Jane M; van Vlijmen-Van Keulen Clarissa; Buxbaum Sarah G; Dudek Doreen M; Tromp Gerard; Ogata Toru; Skunca Magdalena; Sakalihasan Natzi; Pals Gerard; Limet Raymond; MacKean Gerald L; Defawe Olivier; Verloes Alain; Arthur Claudette; Lossing Alan G; Burnett Marjorie; Sueda Taijiro; Kuivaniemi Helena
Genome scan for familial abdominal aortic aneurysm using sex and family history as covariates suggests genetic heterogeneity and identifies linkage to chromosome 19q13.
Circulation 2004;109(17):2103-8.
BACKGROUND: Abdominal aortic aneurysm (AAA) is a relatively common disease, with 1% to 2% of the population harboring aneurysms. Genetic risk factors are likely to contribute to the development of AAAs, although no such risk factors have been identified. METHODS AND RESULTS: We performed a whole-genome scan of AAA using affected-relative-pair (ARP) linkage analysis that includes covariates to allow for genetic heterogeneity. We found strong evidence of linkage (logarithm of odds [LOD] score=4.64) to a region near marker D19S433 at 51.88 centimorgans (cM) on chromosome 19 with 36 families (75 ARPs) when including sex and the number of affected first-degree relatives of the proband (N(aff)) as covariates. We then genotyped 83 additional families for the same markers and typed additional markers for all families and obtained a LOD score of 4.75 (P=0.00014) with sex, N(aff), and their interaction as covariates near marker D19S416 (58.69 cM). We also identified a region on chromosome 4 with a LOD score of 3.73 (P=0.0012) near marker D4S1644 using the same covariate model as for chromosome 19. CONCLUSIONS: Our results provide evidence for genetic heterogeneity and the presence of susceptibility loci for AAA on chromosomes 19q13 and 4q31.

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