Hagedorn Research Institute and Steno Diabetes Center, Niels Steensens Vej 1, Gentofte, Denmark.
Genes Immun. 2009 Dec;10 Suppl 1(Suppl 1):S49-53. doi: 10.1038/gene.2009.91.
To reassess earlier suggested type I diabetes (T1D) associations of the insulin receptor substrate 1 (IRS1) and the paired domain 4 gene (PAX4) genes, the Type I Diabetes Genetics Consortium (T1DGC) evaluated single-nucleotide polymorphisms (SNPs) covering the two genomic regions. Sixteen SNPs were evaluated for IRS1 and 10 for PAX4. Both genes are biological candidate genes for T1D. Genotyping was performed in 2300 T1D families on both Illumina and Sequenom genotyping platforms. Data quality and concordance between the platforms were assessed for each SNP. Transmission disequilibrium testing neither show T1D association of SNPs in the two genes, nor did haplotype analysis. In conclusion, the earlier suggested associations of IRS1 and PAX4 to T1D were not supported, suggesting that they may have been false positive results. This highlights the importance of thorough quality control, selection of tagging SNPs, more than one genotyping platform in high throughput studies, and sufficient power to draw solid conclusions in genetic studies of human complex diseases.
为了重新评估先前提出的胰岛素受体底物 1（IRS1）和配对域 4 基因（PAX4）与 1 型糖尿病（T1D）的关联，1 型糖尿病遗传学联合会（T1DGC）评估了涵盖两个基因组区域的单核苷酸多态性（SNP）。对 IRS1 进行了 16 个 SNP 的评估，对 PAX4 进行了 10 个 SNP 的评估。这两个基因都是 T1D 的生物学候选基因。在 Illumina 和 Sequenom 两种基因分型平台上，对 2300 个 T1D 家族进行了基因分型。对每个 SNP 进行了数据质量和平台间一致性的评估。传递不平衡测试既没有显示 IRS1 和 PAX4 基因的 SNPs 与 T1D 之间存在关联，也没有进行单倍型分析。总之，IRS1 和 PAX4 与 T1D 的先前关联并未得到支持，这表明它们可能是假阳性结果。这突出表明，在人类复杂疾病的遗传研究中，需要进行彻底的质量控制、选择标记 SNP、在高通量研究中使用多个基因分型平台以及具有足够的能力得出可靠的结论。
