Genome scan for familial abdominal aortic aneurysm using sex and family history as covariates suggests genetic heterogeneity and identifies linkage to chromosome 19q13.
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.
Shibamura
Hidenori
H
Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Mich 48201, USA.
Olson
Jane M
JM
van Vlijmen-Van Keulen
Clarissa
C
Buxbaum
Sarah G
SG
Dudek
Doreen M
DM
Tromp
Gerard
G
Ogata
Toru
T
Skunca
Magdalena
M
Sakalihasan
Natzi
N
Pals
Gerard
G
Limet
Raymond
R
MacKean
Gerald L
GL
Defawe
Olivier
O
Verloes
Alain
A
Arthur
Claudette
C
Lossing
Alan G
AG
Burnett
Marjorie
M
Sueda
Taijiro
T
Kuivaniemi
Helena
H
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