Journal
CIRCULATION
Volume 109, Issue 17, Pages 2103-2108Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.CIR.0000127857.77161.A1
Keywords
aorta; aneurysm; genetics; mapping
Funding
- NCRR NIH HHS [RR03655] Funding Source: Medline
- NHGRI NIH HHS [HG01577] Funding Source: Medline
- NHLBI NIH HHS [R01 HL064310, HL64310] Funding Source: Medline
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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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