The genetics of asthma and atopy have been difficult to determine because these diseases are genetically heterogeneous and modified by environment. The pedigrees in our study (n=86) originate in eastern central Finland (Kainuu province). According to census records, this region had only 200 households (2,000 inhabitants) in the mid sixteenth to mid seventeenth centuries. The current population of 100,000 represents the expansion of these founders within the past 400 years. Because this population is relatively homogeneous, we hypothesized that the molecular genetic mechanisms underlying asthma might also have reduced heterogeneity and therefore be easier to dissect than in mixed populations. A recent twin family study supported a strong genetic component for asthma in Finland. We carried out a genome-wide scan for susceptibility loci in asthma in the Kainuu subpopulation. We identified two regions of suggestive linkage and studied them further with higher-density mapping. We obtained evidence for linkage in a 20-cM region of chromosome 7p14-p15 for three phenotypes: asthma, a high level of immunoglobulin E (IgE; atopy) and the combination of the phenotypes. The strongest linkage was seen for high serum IgE (non-parametric linkage (NPL) score 3.9, P=0.0001), exceeding the threshold for genome-wide significance based on simulations. We also observed linkage between this locus and asthma or atopy in two independent data sets.

中文翻译：

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在全基因组人群中通过全基因组扫描揭示了7号染色体上哮喘相关性状的易感性基因座。

哮喘和特应性病的遗传学很难确定，因为这些疾病在遗传上是异质的，并且受到环境的影响。我们研究的谱系（n = 86）起源于芬兰中东部（Kainuu省）。根据人口普查记录，该地区在16世纪中叶到17世纪中叶只有200户家庭（2,000名居民）。目前的100,000人口代表了这些创始人在过去400年中的扩展。由于该人群相对同质，我们假设哮喘的分子遗传机制可能也降低了异质性，因此比混合人群更容易进行解剖。一项最新的双胞胎家庭研究支持了芬兰哮喘的强大遗传成分。我们对Kainuu亚群中的哮喘易感基因座进行了全基因组扫描。我们确定了提示链接的两个区域，并通过更高密度的映射对其进行了进一步研究。我们获得了在7p14-p15染色体的20-cM区域连锁的三种表型的证据：哮喘，高水平的免疫球蛋白E（IgE；特应性）和这些表型的组合。对于高血清IgE，观察到最强的连锁（非参数连锁（NPL）得分3.9，P = 0.0001），超过了基于模拟的全基因组意义的阈值。我们还在两个独立的数据集中观察到了该基因座与哮喘或特应性之间的联系。我们获得了在7p14-p15染色体的20-cM区域连锁的三种表型的证据：哮喘，高水平的免疫球蛋白E（IgE；特应性）和这些表型的组合。对于高血清IgE，观察到最强的连锁（非参数连锁（NPL）得分3.9，P = 0.0001），超过了基于模拟的全基因组意义的阈值。我们还在两个独立的数据集中观察到了该基因座与哮喘或特应性之间的联系。我们获得了在7p14-p15染色体的20-cM区域连锁的三种表型的证据：哮喘，高水平的免疫球蛋白E（IgE；特应性）和这些表型的组合。对于高血清IgE，观察到最强的连锁（非参数连锁（NPL）得分3.9，P = 0.0001），超过了基于模拟的全基因组意义的阈值。我们还在两个独立的数据集中观察到了该基因座与哮喘或特应性之间的联系。