Abstract
The genetics of asthma and atopy have been difficult to determine because these diseases are genetically heterogeneous and modified by environment. The pedigrees in our study (n=86) originate in eastern central Finland (Kainuu province). According to census records, this region had only 200 households (2,000 inhabitants) in the mid sixteenth to mid seventeenth centuries. The current population of 100,000 represents the expansion of these founders within the past 400 years. Because this population is relatively homogeneous1,2, we hypothesized that the molecular genetic mechanisms underlying asthma might also have reduced heterogeneity and therefore be easier to dissect than in mixed populations. A recent twin family study supported a strong genetic component for asthma in Finland3. We carried out a genome-wide scan for susceptibility loci in asthma in the Kainuu subpopulation. We identified two regions of suggestive linkage and studied them further with higher-density mapping. We obtained evidence for linkage in a 20-cM region of chromosome 7p14–p15 for three phenotypes: asthma, a high level of immunoglobulin E (IgE; atopy) and the combination of the phenotypes. The strongest linkage was seen for high serum IgE (non-parametric linkage (NPL) score 3.9, P=0.0001), exceeding the threshold for genome-wide significance based on simulations. We also observed linkage between this locus and asthma or atopy in two independent data sets.
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Acknowledgements
We thank H. Laitinen, J. Ignatius, L. Rajasalo, P. Pajunen and S. Lindh for help in organizing the sample collection drive in Kainuu, and S. Knaappila, M. Nissinen, C. Vestergaard, E. Brown and R. Koyoumjian for genotyping work. This study was supported in Finland by Academy of Finland, EU/BIOMED2 (BMH4-CT97-2486), Helsinki University Central Hospital Research Funds, and Sigrid Juselius Foundation; and in Canada and the USA by a research grant from Bristol-Myers Squibb, Millennium Pharmaceutical Inc. and Affymetrix. T.L. received scholarships from the Finnish Lung and Health Association, Finnish Anti-Tuberculosis Association Foundation, Academy of Finland and UCB Institute of Allergy. C.L. received a CLA/Merck Frosst fellowship from the Canadian Thoracic Society-Medical Section of the Canadian Lung Association. T.J.H. is recipient of a Clinician Scientist Award from the Medical Research Council of Canada.
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Laitinen, T., Daly, M., Rioux, J. et al. A susceptibility locus for asthma-related traits on chromosome 7 revealed by genome-wide scan in a founder population. Nat Genet 28, 87–91 (2001). https://doi.org/10.1038/ng0501-87
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DOI: https://doi.org/10.1038/ng0501-87
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