Indication of linkage and genetic heterogeneity of asthma according to age at onset on chromosome 7q in 107 French EGEA families
Indication of linkage and genetic heterogeneity of asthma according to age at onset on chromosome 7q in 107 French EGEA families
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DOI：
10.1038/sj.ejhg.5200732
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发表时间：
2001-11-01
影响因子：
5.2
通讯作者：
Demenais, F
中科院分区：
文献类型：
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作者：
Dizier, MH;Besse-Schmittler, C;Demenais, F
一般认为，发病年龄较早与较强的遗传成分有关。我们在这里的目的是研究哮喘的连锁和遗传异质性，后者对应于根据哮喘发病年龄推测的连锁基因的不同基因型相对风险。这项分析是在107个至少有两个哮喘兄弟姐妹的法国Egea家庭中进行的，考虑到157个标记，这些标记是我们之前基因组筛查的一部分，使用TTS(三角检验统计量)已经开发出来用于检测连锁和同胞内遗传异质性。这项测试已经应用于38对哮喘发病年龄不一致的哮喘同胞。为了证实遗传异质性的存在，我们还使用了预分样本检验(PST)，比较了哮喘同胞相容(67)和不相容(38)的标记等位基因在发病年龄的IBD(下降同一性)分布。在我们的哮喘同胞样本中，用于发病年龄的截断点是4岁，发病的中位年龄。Tts(P=0.005，多项检验校正后P>；0.5)和Pst(校正后P=0.0001，校正后P=0.015)两个检验均表明位于染色体7q上的一个区域(距Pter109 cM)存在连锁和遗传异质性。这些结果表明，7q上的一个遗传因素与哮喘有关，其基因相对风险因发病年龄不同而不同。
It is generally believed that an early age at the onset: of disease is:associated with a stronger genetic component. Our aim here was to investigate both linkage and genetic heterogeneity of asthma, the latter corresponding to different genotype relative risks of a putative linked gene according to age at onset of asthma. This analysis was conducted in 107, French EGEA families with at least two asthmatic siblings, considering 157 markers that were part of our previous genome screen, using the TTS (the Triangle Test Statistic) which has been developed to detect both linkage and intra-sibpair genetic heterogeneity. This test has been applied to 38 asthmatic sib-pairs discordant for age at the onset of asthma. To confirm the existence of genetic heterogeneity, we also used the predivided sample test (PST) which compares the IBD (identity by descent) distribution of marker alleles between asthmatic sib-pairs concordant (67) and discordant (38) for the age at onset. The cutoff point used for the age at onset was 4 years, the median age at, onset in our sample of asthmatic sibs. Linkage and genetic heterogeneity for a region located on chromosome 7q (at 109 cM from pter) were indicated by both tests, TTS (P = 0.005, P > 0.5 after correction for multiple testing) and PST (P = 0.0001, 0.015 after correction). These results suggest a genetic factor on 7q involved in asthma with genotype relative risks differing according to age at: onset of disease.