Dizier M H, 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
INSERM U155, Université Paris 7, Paris, France; INSERM EPI 00-06, H opital St Louis, Paris, France.
Am J Respir Crit Care Med. 2000 Nov;162(5):1812-8. doi: 10.1164/ajrccm.162.5.2002113.
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.
作为法国EGEA研究的一部分，对107个核心家庭进行了全基因组搜索，这些家庭中至少有两个患哮喘的兄弟姐妹。采用两阶段分析策略，将107个家庭分为两个独立的子集，分别为46个家庭和61个家庭，在第一组家庭中检测到的所有区域都在第二组中进行复制测试。此外，在总样本中检查了不同人群已发表的基因组扫描报告的所有区域。在第一组家庭中总共检测了254个标记，第二组检测了其中的70%。通过无模型方法研究哮喘及四种与哮喘相关的表型的连锁关系：支气管反应性（BR）、皮肤试验反应、总免疫球蛋白E（IgE）水平和嗜酸性粒细胞计数。两阶段分析检测到三个区域：与IgE相关的11p13、与嗜酸性粒细胞相关的12q24以及与哮喘和皮肤试验相关的17q12 - 21。在已发表的基因组筛查报告的区域中，在107个法国EGEA家庭中发现了七个：三个已通过两阶段分析检测到，分别是11p13（p = 0.005）、12q24（p = 0.0008）和17q12 - 21（p = 0.001），另外四个是：与哮喘相关的1p31（p = 0.005）、与IgE相关的11q13（p = 0.006）、与嗜酸性粒细胞相关的13q31（p = 0.001）以及与BR相关的19q13（p = 0.02）。
