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Meta-analysis for linkage to asthma and atopy in the chromosome 5q31-33 candidate region.

Meta-analysis for linkage to asthma and atopy in the chromosome 5q31-33 candidate region.
Meta-analysis for linkage to asthma and atopy in the chromosome 5q31-33 candidate region.
Asthma is a common, complex human disease. Gene discovery in asthma has been complicated by substantial etiological heterogeneity, the possibility of genes of small effect and the concomitant requirement for large sample sizes. Linkage to asthma phenotypes has been investigated most intensively in the 5q chromosomal region, although results have been inconsistent across studies and all studies have had modest sample sizes. One potential solution to these issues is to combine data from multiple studies in a retrospective meta-analysis by pooling either summary statistics or raw data. The International Consortium on Asthma Genetics combined data from 11 data sets (n = 6277 subjects) to investigate evidence for linkage of 35 markers spanning the cytokine cluster on chromosome 5q31–33 to 'asthma' dichotomy and total serum immunoglobulin E (IgE) levels. Chromosome 5q markers typed in different centers were integrated into a consensus map to facilitate effective data pooling. Multipoint linkage analyses using a new Haseman–Elston method were performed with all data sets pooled together, and also separately with the resulting linkage statistics pooled by meta-analytic methods. Our results did not provide any evidence significant at the 5% level that loci conferring susceptibility to asthma or atopy are present in the 5q31–33 region; however, there was some weak evidence (empirical P = 0.077) of linkage to asthma affection. This study suggests that loci in 5q31–33 have at most a modest effect on susceptibility to asthma or total serum IgE levels, may not be detectable or present in all human populations and are difficult to detect even using combined linkage evidence from 2400–2600 full sibling pairs.
891-99
Palmer, Lyle J.
089fb1c1-12e1-4ece-9bfa-7b404cee4772
Barnes, Kathleen C.
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Burton, Paul R.
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Chen, Hong
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Cookson, William O.C.M.
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Deichmann, Klaus A.
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Elston, Robert C.
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Holloway, John W.
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Jacobs, Kevin B.
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Laitinen, Tarja
b1182047-4f8f-4d6b-8d90-b6cf13009f5a
Wjst, Matthias
bb5da074-3243-4e82-a36b-197a4df5a2b8
Collaborative Study on the Genetics of Asthma
Palmer, Lyle J.
089fb1c1-12e1-4ece-9bfa-7b404cee4772
Barnes, Kathleen C.
0bb71f7a-f286-4622-af49-bac7b2ec108f
Burton, Paul R.
14b36fad-9036-4002-8427-c53e9d6dc781
Chen, Hong
408a190d-f7b1-4668-a856-9a2afbcd95c3
Cookson, William O.C.M.
f25b485f-af7a-499d-b522-169e5c991f18
Deichmann, Klaus A.
21e0265b-7bdc-4fff-b596-d9f7e3a1d0a1
Elston, Robert C.
751e7349-2331-49c5-aab1-9f8e61e475a8
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Jacobs, Kevin B.
88f573f4-96e6-40fb-aa6a-65969de0247f
Laitinen, Tarja
b1182047-4f8f-4d6b-8d90-b6cf13009f5a
Wjst, Matthias
bb5da074-3243-4e82-a36b-197a4df5a2b8

Palmer, Lyle J., Barnes, Kathleen C., Burton, Paul R., Chen, Hong, Cookson, William O.C.M., Deichmann, Klaus A., Elston, Robert C., Holloway, John W., Jacobs, Kevin B., Laitinen, Tarja and Wjst, Matthias , Collaborative Study on the Genetics of Asthma (2001) Meta-analysis for linkage to asthma and atopy in the chromosome 5q31-33 candidate region. Human Molecular Genetics, 10 (8), 891-99. (doi:10.1093/hmg/10.8.891). (PMID:21523954)

Record type: Article

Abstract

Asthma is a common, complex human disease. Gene discovery in asthma has been complicated by substantial etiological heterogeneity, the possibility of genes of small effect and the concomitant requirement for large sample sizes. Linkage to asthma phenotypes has been investigated most intensively in the 5q chromosomal region, although results have been inconsistent across studies and all studies have had modest sample sizes. One potential solution to these issues is to combine data from multiple studies in a retrospective meta-analysis by pooling either summary statistics or raw data. The International Consortium on Asthma Genetics combined data from 11 data sets (n = 6277 subjects) to investigate evidence for linkage of 35 markers spanning the cytokine cluster on chromosome 5q31–33 to 'asthma' dichotomy and total serum immunoglobulin E (IgE) levels. Chromosome 5q markers typed in different centers were integrated into a consensus map to facilitate effective data pooling. Multipoint linkage analyses using a new Haseman–Elston method were performed with all data sets pooled together, and also separately with the resulting linkage statistics pooled by meta-analytic methods. Our results did not provide any evidence significant at the 5% level that loci conferring susceptibility to asthma or atopy are present in the 5q31–33 region; however, there was some weak evidence (empirical P = 0.077) of linkage to asthma affection. This study suggests that loci in 5q31–33 have at most a modest effect on susceptibility to asthma or total serum IgE levels, may not be detectable or present in all human populations and are difficult to detect even using combined linkage evidence from 2400–2600 full sibling pairs.

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Published date: 1 April 2001

Identifiers

Local EPrints ID: 192085
URI: http://eprints.soton.ac.uk/id/eprint/192085
PURE UUID: c16bfd0c-0cd1-48db-a730-81756fd6e9b3
ORCID for John W. Holloway: ORCID iD orcid.org/0000-0001-9998-0464

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Date deposited: 29 Jun 2011 13:55
Last modified: 15 Mar 2024 02:56

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Contributors

Author: Lyle J. Palmer
Author: Kathleen C. Barnes
Author: Paul R. Burton
Author: Hong Chen
Author: William O.C.M. Cookson
Author: Klaus A. Deichmann
Author: Robert C. Elston
Author: Kevin B. Jacobs
Author: Tarja Laitinen
Author: Matthias Wjst
Corporate Author: Collaborative Study on the Genetics of Asthma

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