A genome-wide association scan for asthma in a general Australian population.
To date, almost every chromosome has been implicated in genetic susceptibility to asthma to some degree. When compared with single nucleotide polymorphism, microsatellite markers exhibit high levels of heterozygosity and therefore provide higher statistical power in association. The objective of this study was to perform a genome-wide association study using 23,465 in-house microsatellite markers to detect asthma susceptibility regions in the Busselton population. In this study, three separate pooled DNA screenings yielded 18 markers with significantly different estimated frequencies in the three separate "case and control" pools: each pool consisting of 60 males and 60 females. These markers were evaluated by individual typing in 360 cases and 360 controls. Two markers showed significant differences between cases and controls (P = 0.001 and P = 0.003). Regions surrounding the two markers were subjected to high-density association mapping with a total of 14 additional markers. We were able to confirm and fine map the association in these two regions by typing 14 additional microsatellite markers (1805A09 (D18S0325i), P = 0.002; 1806D05 (D18S0181i), P = 0.001). Each region contains a predicted gene that showed strong associations with asthma. Further studies are underway to characterize the novel candidate asthma susceptibility genes identified in this genome-wide study.
Hui
J
J
Western Australian Institute for Medical Research and UWA Centre for Medical Research, B Block, QEII Medical Centre, The University of Western Australia, Nedlands, WA, 6009, Australia. jhui@cyllene.uwa.edu.au
Oka
A
A
James
A
A
Palmer
L J
LJ
Musk
A W
AW
Beilby
J
J
Inoko
H
H
D000328:Adult; D001249:Asthma / Q000453:epidemiology / Q000235:genetics*; D001315:Australia / Q000453:epidemiology; D016022:Case-Control Studies; D002874:Chromosome Mapping; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D003430:Cross-Sectional Studies; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D008040:Genetic Linkage / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D005838:Genotype; D006306:Health Surveys; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
D017931:DNA Primers