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Am. J. Respir. Crit. Care Med., Volume 162, Number 5, November 2000, 1812-1818

Genome Screen for Asthma and Related Phenotypes in the French EGEA Study

MARIE-HÉLÈNE DIZIER, CÉLINE BESSE-SCHMITTLER, MICHEL GUILLOUD-BATAILLE, ISABELLA ANNESI-MAESANO, MEKKI BOUSSAHA, JEAN BOUSQUET, DENIS CHARPIN, ANNA DEGIOANNI, FRÉDÉRIC GORMAND, ALAIN GRIMFELD, JOËLLE HOCHEZ, GINA HYNE, ALAIN LOCKHART, MICHÈLE LUILLIER-LACOMBE, RÉGIS MATRAN, FLAVIE MEUNIER, FRANÇOISE NEUKIRCH, YVES PACHECO, VÉRONIQUE PARENT, EVELYNE PATY, ISABELLE PIN, CHRISTOPHE PISON, PIERRE SCHEINMANN, NICOLE THOBIE, DANIEL VERVLOET, FRANCINE KAUFFMANN, JOSUÉ FEINGOLD, MARK LATHROP, and FLORENCE DEMENAIS

INSERM U155, Université Paris 7, Paris, France; INSERM EPI 00-06, Hôpital St Louis, Paris, France; INSERM U472, Villejuif, France; Clinique des Maladies Respiratoires, INSERM U454, Hôpital Arnaud de Villeneuve, Montpellier, France; Service de Pneumologie,-Allergologie, Hôpital Nord, Marseille, France; Service de Pneumologie, Centre Hospitalier Lyon-Sud, Pierre Benite, France; Centre de Diagnostic et Traitement de l'Asthme, Hôpital Trousseau, Paris, France; Wellcome Trust Center of Human Genetics, Oxford, United Kingdom; Service d'Exploration Fonctionnelle, Hôpital Cochin, Paris, France; Laboratoire d'Exploration Fonctionnelle, Hôpital Calmette, Lille, France; INSERM U408, Paris, France; Service de Pneumologie Infantile, Hôpital Necker, Paris, France; Service Pneumologie, CHU Michallon, Grenoble, France; Service de Pneumo-Allergologie, Hôpital Ste Marguerite, Marseille, France; and Centre National de Génotypage, Evry, France

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) for IgE, 13q31 (p = 0.001) for eosinophils, and 19q13 (p = 0.02) for BR.




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