OBJECTIVE One of four American cancer patients dies of lung cancer. Environmental factors such as tobacco smoking are known to affect lung cancer risk. However, there is a genetic factor to lung cancer risk as well. Here, we perform parametric linkage analysis on family-based genotype data in an effort to find genetic loci linked to the disease. METHODS 197 individuals from families with a high-risk history of lung cancer were recruited and genotyped using an Illumina array. Parametric linkage analyses were performed using an affected-only phenotype model with an autosomal dominant inheritance using a disease allele frequency of 0.01. Three types of analyses were performed: single variant two-point, collapsed haplotype pattern variant two-point, and multipoint analysis. RESULTS Five novel genome-wide significant loci were identified at 18p11.23, 2p22.2, 14q13.1, 16p13, and 20q13.11. The families most informative for linkage were also determined. CONCLUSIONS The 5 novel signals are good candidate regions, containing genes that have been implicated as having somatic changes in lung cancer or other cancers (though not in germ line cells). Targeted sequencing on the significant loci is planned to determine the causal variants at these loci.

中文翻译：

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参数连锁分析确定了家族性肺癌的五个新的全基因组显着位点。

目标四名美国癌症患者中有一名死于肺癌。众所周知，吸烟等环境因素会影响肺癌风险。然而，肺癌风险也有遗传因素。在这里，我们对基于家族的基因型数据进行参数连锁分析，以寻找与疾病相关的基因位点。方法 招募了来自有肺癌高危家族史的 197 个人，并使用 Illumina 阵列进行基因分型。使用具有常染色体显性遗传的仅受影响的表型模型进行参数连锁分析，使用疾病等位基因频率为 0.01。进行了三种类型的分析：单变体两点分析、折叠单倍型模式变体两点分析和多点分析。结果 在 18p11.23 处鉴定了五个新的全基因组显着位点，2p22.2、14q13.1、16p13 和 20q13.11。还确定了关联信息最丰富的家族。结论 这 5 个新信号是很好的候选区域，其中包含在肺癌或其他癌症（尽管不是在生殖系细胞中）具有体细胞变化的基因。计划对重要基因座进行靶向测序以确定这些基因座的因果变异。