A genome-wide search for asthma susceptibility loci in ethnically diverse populations (original) (raw)
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- Published: 01 April 1997
Nature Genetics volume 15, pages 389–392 (1997)Cite this article
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Abstract
Asthma is an inflammatory airwaysdisease associated with intermittent respiratory symptoms, bronchial hyperresponsiveness (BHR) and reversible airflow obstruction and is phenotypically heterogeneous1,2. Patterns of clustering and segregation analyses in asthma families have suggested a genetic component to asthma3–6. Previous studies reported linkage of BHR and atopy to chromosomes 5q (refs 7–9), 6p (refs 10–12), 11q (refs 13–15), 14q (ref. 16), and 12q (ref. 17) using candidate gene approaches. However, the relative roles of these genes in the pathogenesis of asthma or atopy are difficult to assess outside of the context of a genome-wide search. One genome-wide search in atopic sib pairs has been reported18, however, only 12% of their subjects had asthma. We conducted a genome-wide search in 140 families with ≥2 asthmatic sibs, from three racial groups and report evidence for linkage to six novel regions: 5p15 (P= 0.0008) and 17p11.1–q11.2 (/> = 0.0015) in African Americans; 11p15 (P = 0.0089) and 19q13 (P = 0.0013) in Caucasians; 2q33 (P = 0.0005) and 21q21 (P = 0.0040) in Hispanics. Evidence for linkage was also detected in five regions previously reported to be linked to asthma-associated phenotypes: 5q23–31 (P = 0.0187), 6p21.3–23 (P = 0.0129), 12q14–24.2 (P = 0.0042), 13q21.3–qter (P = 0.0014), and 14q11.2–13 (P = 0.0062) in Caucasians and 12q14–24.2 (P = 0.0260) in Hispanics.
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22 October 2020
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References
- NHLBI. International concensus report of diagnosis and treatment of asthma: National Heart, Lung, and Blood Institute, Publication No. 92-3091, (1992).
- Sheffer, A.L. et al. Guidelines for the diagnosis and management of asthma. J. Allergy Clin. Immunol.88, 425–534 (1991).
Article Google Scholar - Duffy, D.L., Martin, N.G. & Battistutta, D. Genetics of asthma and hay fever in Australian twins. Am. Rev. Respir. Dis.142, 1351–1358 (1990).
Article CAS Google Scholar - Edfors-Lubs, M.-L. Allergy in 7000 twin pairs. Acta. Allergol.26, 249–285 (1971).
Article CAS Google Scholar - Hopp, R.J., Bewtra, A.K., Biven, R., Nair, N.M. & Townley, R.G. Bronchial reactivity pattern in nonasthmatic parents of asthmatics. Ann. Allergy61, 184–186 (1988).
CAS PubMed Google Scholar - Sibbald, B. & Turner-Warwick, M. Factors influencing the prevalence of asthma among first degree relatives of extrinsic and intrinsic asthmatics. Thorax34, 332–337 (1979).
Article CAS Google Scholar - Marsh, D.G. et al. Linkage analysis of IL4 and other chromosome 5q31.1 markers and total serum immunoglobulin E concentrations. Science264, 1152–1156 (1994).
Article CAS Google Scholar - Meyers, D.A. et al. Evidence for a locus regulating total serum IgE levels map to chromosome 5. Genomics23, 464–470 (1994).
Article CAS Google Scholar - Postma, D.S. et al. Genetic suseptibility to asthma-bronchial hyperresponsiveness coinherited with a major gene for atopy. NewEngl. J. Med.333, 894–900 (1995).
Article CAS Google Scholar - Blumenthal, M.N. et al. Extended major HLA-DR2, [HLA-B7, SC31, DR2], and [HLA-B8, SC01, DR3] naplotypes distinguish subjects with asthma from those with only rhinitis in ragweed pollen allergy.J. Immunol.148, 411–16 (1992).
CAS PubMed Google Scholar - Marsh, D.G. & Blumenthal, M.N. Genetic and Environmental Factors in Clinical Allergy (University of Minnesota Press, Minneapolis, 1990).
- Young, R.P. et al. HLA-DR and HLA-DP genotypes and immunoglobulin E responses to common major allergens.Clin. Exper. Allergy24, 431–439 (1994).
Article CAS Google Scholar - Cookson, W.O.C.M., Sharp, P.A., Faux, J.A. & Hopkin, J.M. Linkage between immunoglobulin E responses underlying asthma and rhinitis and chromosome 11q. Lancet1, 1292–1295 (1989).
Article CAS Google Scholar - Shirakawa, T. et al. Linkage between IgE responses underlying asthma and rhinitis (Atopy) and chromosome 11q in Japanese families. Cytogenet. Cell Genet.58, 1970–1971 (1991).
Google Scholar - Shirakawa, T. et al. Association between atopy and variants of the subunit of the high-affinity immunoglobulin E receptor. Nature Genet.7, 125–130 (1994).
Article CAS Google Scholar - Moffatt, M.F. et al. Genetic linkage of T-cell receptor α/δ complex to specific IgE responses. Lancet343, 1597–1600 (1994).
Article CAS Google Scholar - Barnes, K.C. et al. Linkage of asthma and total serum IgE concentration to markers on chromosome 12q: evidence from Afro-Carribean and Caucasian populations. Genomics37, 41–50 (1996).
Article CAS Google Scholar - Daniels, S.E. et al. A genome-wide search for quantitative trait loci underlying asthma. Nature383, 247–250 (1996).
Article CAS Google Scholar - Weiss, S.T. et al. Airway responsiveness in a population sample of adults and children. Am. Rev. Respir. Dis. S.T.129, 898–902 (1984).
CAS Google Scholar - Suarez, B.K., Hampe, C.L. & Van Eerdewegh, P. in Genetic Approaches to Mental Disorders (eds Gershon, E.S. & Cloninger, C.R.) 23–46 (American Psychiatric Press, Washington, D.C 1994).
Google Scholar - Lander, E. & L Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nature Genet.11, 241–247 (1995).
Article CAS Google Scholar - ATS Standardization of spirometry — 1987 update. Am. J. Respir. Crit. Care Med.153, 1285–1298 (1987).
- Lapp, N.L., Amandus, H.E., Hall, R. & Morgan, W.K. C Lung volumes and flow rates in black and white subjects. Thorax29, 185–188 (1974).
Article CAS Google Scholar - Chai, H. et al. Standardization of bronchial inhalation challenge procedures. J. Allergy Clin. Immunol.56, 323–327 (1975).
Article CAS Google Scholar - Chatham, M., Bleecker, E.R., Mason, P., Smith, P.L. & Norman, P. A screening test for airways reactivity — an abbreviated methacholine inhalation challenge.Chest82, 15–18 (1982).
Article CAS Google Scholar - Kruglyak, L., Daly, M.J., Reeve-Daly, M.P. & Lander, E.S. Parametric and nonparametric linkage analysis: a unified multipoint approach.Am. J. Hum. Genet.58, 1347–1363 (1996).
CAS PubMed PubMed Central Google Scholar
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A genome-wide search for asthma susceptibility loci in ethnically diverse populations .Nat Genet 15, 389–392 (1997). https://doi.org/10.1038/ng0497-389
- Received: 05 November 1996
- Accepted: 26 February 1997
- Issue Date: 01 April 1997
- DOI: https://doi.org/10.1038/ng0497-389