title: Genome scan for familial abdominal aortic aneurysm using sex and family history as covariates suggests genetic heterogeneity and identifies linkage to chromosome 19q13.
abstract: 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.
  
  
  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.
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Mich 48201, USA.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Shibamura
authors.forename: Jane M
authors.initials: JM
authors.lastname: Olson
authors.forename: Clarissa
authors.initials: C
authors.lastname: van Vlijmen-Van Keulen
authors.forename: Sarah G
authors.initials: SG
authors.lastname: Buxbaum
authors.forename: Doreen M
authors.initials: DM
authors.lastname: Dudek
authors.forename: Gerard
authors.initials: G
authors.lastname: Tromp
authors.forename: Toru
authors.initials: T
authors.lastname: Ogata
authors.forename: Magdalena
authors.initials: M
authors.lastname: Skunca
authors.forename: Natzi
authors.initials: N
authors.lastname: Sakalihasan
authors.forename: Gerard
authors.initials: G
authors.lastname: Pals
authors.forename: Raymond
authors.initials: R
authors.lastname: Limet
authors.forename: Gerald L
authors.initials: GL
authors.lastname: MacKean
authors.forename: Olivier
authors.initials: O
authors.lastname: Defawe
authors.forename: Alain
authors.initials: A
authors.lastname: Verloes
authors.forename: Claudette
authors.initials: C
authors.lastname: Arthur
authors.forename: Alan G
authors.initials: AG
authors.lastname: Lossing
authors.forename: Marjorie
authors.initials: M
authors.lastname: Burnett
authors.forename: Taijiro
authors.initials: T
authors.lastname: Sueda
authors.forename: Helena
authors.initials: H
authors.lastname: Kuivaniemi
mesh_terms: D000328:Adult; D000368:Aged; D017544:Aortic Aneurysm, Abdominal / Q000453:epidemiology / Q000235:genetics*; D002877:Chromosomes, Human / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D005260:Female; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D010641:Phenotype; D016133:Polymerase Chain Reaction