Genome screen for asthma and related phenotypes in the French EGEA study

被引:175
作者
Dizier, MH
Besse-Schmittler, C
Guilloud-Bataille, M
Annesi-Maesano, I
Boussaha, M
Bousquet, J
Charpin, D
Degioanni, A
Gormand, F
Grimfeld, A
Hochez, J
Hyne, G
Lockhart, A
Luillier-Lacombe, M
Matran, R
Meunier, F
Neukirch, F
Pacheco, Y
Parent, V
Paty, E
Pin, I
Pison, C
Scheinmann, P
Thobie, N
Vervloet, D
Kauffmann, F
Feingold, J
Lathrop, M
Demenais, F
机构
[1] Univ Paris 07, INSERM U155, Paris, France
[2] Hop St Louis, INSERM EPI 0006, Paris, France
[3] INSERM U472, Villejuif, France
[4] Hop Arnaud de Villeneuve, INSERM U454, Clin Malad Resp, Montpellier, France
[5] Ctr Hosp Lyon Sud, Serv Pneumol, Pierre Benite, France
[6] Hop Nord Marseille, Serv Pneumol Allergol, Marseille, France
[7] Hop Trousseau, Ctr Diagnost & Traitement Asthme, F-75571 Paris, France
[8] Wellcome Trust Ctr Human Genet, Oxford, England
[9] Hop Cochin, Serv Explorat Fonctionnelle, F-75674 Paris, France
[10] Hop Calmette, Lab Explorat Fonctionnelle, Lille, France
[11] INSERM U408, Paris, France
[12] Hop Necker Enfants Malad, Serv Pneumol Infantile, Paris, France
[13] CHU Michallon, Serv Pneumol, Grenoble, France
[14] Hop St Marguerite, Serv Pneumoallergol, Marseille, France
[15] Ctr Natl Genotypage, Evry, France
关键词
D O I
10.1164/ajrccm.162.5.2002113
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
A genome-wide search was conducted in 107 nuclear families with at least two siblings with asthma, as part of the French EGEA study. A two-stage analysis strategy was applied to the 107 families divided into two independent subsets of 46 and 61 families, where all regions detected in the first set of families were tested for replication in the second set. In addition, all regions reported by published genome scans in different populations were examined in the total sample. A total of 254 markers were typed in the first set of families and 70% of them in the second set. Linkage was investigated by model-free methods for asthma and four asthma-related phenotypes: bronchial responsiveness (BR), skin test response, total immunoglobulin E (IgE) levels, and eosinophil count. The two-stage analysis led to the detection of three regions: 11p13 for IgE, 12q24 for eosinophils, and 17q12-21 for asthma and skin tests, Among the regions reported by published genome screens, seven were found in the 107 French EGEA families: three being already detected by the two-stage analysis, 11p13 (p = 0.005), 12q24 (p = 0.0008), and 17q12-21 (p = 0.001), and four additional ones, 1p31 (p = 0.005) for asthma, 11q13 (p = 0.006) far IgE, 13q31 (p = 0.001) for eosinophils, and 19q13 (p = 0.02) for BR.
引用
收藏
页码:1812 / 1818
页数:7
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