Meta-analysis for linkage to asthma and atopy in the chromosome 5q31-33 candidate region |
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| Authors: | Palmer L J,Barnes K C,Burton P R,Chen H,Cookson W O Collaborative Study on the Genetics of Asthma,Deichmann K A,Elston R C,Holloway J W,Jacobs K B,Laitinen T,Wjst M |
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| Affiliation: | 1Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Harvard University, Boston, MA 02115, USA, 2Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA, 3Genetic Epidemiology Unit, TVW Telethon Institute for Child Health Research, Perth, Australia, 4Johns Hopkins University, Baltimore, MD, USA, 5Genetic Epidemiology Unit, Department of Epidemiology and Public Health, University of Leicester, Leicester, UK, 6Department of Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China, 7Asthma Genetics Group, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, UK, 8Terri Beaty: Johns Hopkins University, Baltimore, MD, USA; Eugene Bleecker: University of Maryland, Baltimore, MD, USA; Malcolm Blumenthal: University of Minnesota, Minneapolis, MN, USA; Carole Ober: University of Chicago, Chicago, IL, USA; Stephen Rich: Wake Forest University School of Medicine, Winston-Salem, NC, USA, 9Childrens’ Hospital, University of Freiburg, Germany, 10Asthma Genetics Group, Human Genetics Research Division, Duthie Building, Southampton General Hospital, UK, 11Department of Medical Genetics, University of Helsinki, Finland and 12German Asthma Genetics Group: Institute of Epidemiology, GSF National Research Center for Environment and Health, Neuherberg, Germany |
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| Abstract: | Asthma is a common, complex human disease. Gene discovery inasthma has been complicated by substantial etiological heterogeneity,the possibility of genes of small effect and the concomitantrequirement for large sample sizes. Linkage to asthma phenotypeshas been investigated most intensively in the 5q chromosomalregion, although results have been inconsistent across studiesand all studies have had modest sample sizes. One potentialsolution to these issues is to combine data from multiple studiesin a retrospective meta-analysis by pooling either summary statisticsor raw data. The International Consortium on Asthma Genetics combined data from 11 data sets (n = 6277 subjects) to investigateevidence for linkage of 35 markers spanning the cytokine clusteron chromosome 5q3133 to asthma dichotomyand total serum immunoglobulin E (IgE) levels. Chromosome 5qmarkers typed in different centers were integrated into a consensusmap to facilitate effective data pooling. Multipoint linkageanalyses using a new HasemanElston method were performedwith all data sets pooled together, and also separately withthe resulting linkage statistics pooled by meta-analytic methods.Our results did not provide any evidence significant at the5% level that loci conferring susceptibility to asthma or atopyare present in the 5q3133 region; however, there wassome weak evidence (empirical P = 0.077) of linkage toasthma affection. This study suggests that loci in 5q3133have at most a modest effect on susceptibility to asthma ortotal serum IgE levels, may not be detectable or present inall human populations and are difficult to detect even usingcombined linkage evidence from 24002600 full siblingpairs. + To whom correspondence should be addressed. Tel: +1 617 5250872; Fax: +1 617 525 0958; Email: reljp@channing.harvard.edu. |
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