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A genome-wide association scan for asthma in a general Australian population

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Abstract

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.

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Acknowledgments

This work was supported by a Grant-in-Aid for Science Research from the Japanese Ministry of Education and by Tokai University of Medicine, Japan. J. Hui is supported by a post-doctoral fellowship from Japan Society for the Promotion of Science (JSPS), Tokai University of Medicine and the Western Australia Institute for Medical Research. The author would like to thank the Busselton Population Medical Research Foundation and the Busselton community for their participation in the study. We also thank Euzebiusz Jamrozik and Mark Divitini for statistical advices and Kaori Yamaguchi, Hiromi Kamura, Erika Matsushita and Hiromi Takase at the Department of Molecular Life Science, Tokai University School of Medicine, for technical assistance in the genome-wide screens.

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Authors and Affiliations

  1. 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

    J. Hui & L. J. Palmer

  2. Department of Molecular Life Science, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa, 259-1193, Japan

    J. Hui, A. Oka & H. Inoko

  3. Western Australian Sleep Disorders Research Institute, Sir Charles Gairdner Hospital, Nedlands, WA, 6009, Australia

    A. James

  4. Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, WA, 6009, Australia

    A. W. Musk

  5. Clinical Biochemistry, PathWest Laboratory Medicine Western Australia, QEII Medical site Nedlands, Australia School of Surgery and Pathology, University of Western Australia, Nedlands, WA, 6009, Australia

    J. Beilby

  6. School of Surgery and Pathology, University of Western Australia, Nedlands, WA, 6009, Australia

    J. Beilby

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  1. J. Hui
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Correspondence to J. Hui.

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Hui, J., Oka, A., James, A. et al. A genome-wide association scan for asthma in a general Australian population. Hum Genet 123, 297–306 (2008). https://doi.org/10.1007/s00439-008-0477-9

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