Type 1 diabetes mellitus (TIDM) has a multifactorial etiology, with major genetic-susceptibility determinants located in the HLA and insulin-gene (INS) regions. Linkage data implicating other disease-susceptibility loci are conflicting. This is likely due to (1) the limited power for detection of contributions of additional susceptibility loci, given the limited number of informative families available for study, (2) factors such as genetic heterogeneity between populations, and (3) potential gene-gene and gene-environment interactions. To circumvent some of these problems, we have conducted a genomewide linkage analysis for T1DM-susceptibility loci in 408 multiplex families from Scandinavia, a population expected to be homogeneous for genetic and environmental factors. In addition to verifying the HLA and INS susceptibility loci, the study provides confirmation of IDDM15 on chromosome 6q21. Suggestive evidence of additional susceptibility loci was found on chromosomes 2p, 5q, and 16p. For some loci, the support for linkage increased substantially when families were stratified on the basis of HLA or INS genotypes, with statistically significant heterogeneity between the stratified subgroups. Our data support both the existence of non-HLA genes of significance for T1DM and interaction between HLA and non-HLA loci in the determination of the T1DM phenotype.

中文翻译：

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斯堪的纳维亚家庭对1型糖尿病易感性的全基因组扫描：鉴定具有相互作用证据的新基因座。

1型糖尿病（TIDM）具有多种病因，主要的遗传易感性决定因素位于HLA和胰岛素基因（INS）地区。暗示其他疾病易感基因座的连锁数据存在冲突。这可能是由于（1）鉴于可供研究的信息性家庭数量有限，检测其他易感基因座的贡献的能力有限；（2）群体之间的遗传异质性等因素；（3）潜在的基因基因和基因-环境相互作用。为了避免这些问题，我们对来自斯堪的纳维亚半岛的408个多重家族中的T1DM易感性基因座进行了全基因组连锁分析，该群体的遗传和环境因素预计是同质的。除了验证HLA和INS易感性基因座外，这项研究证实了在染色体6q21上IDDM15。在2p，5q和16p染色体上发现了其他易感基因座的暗示性证据。对于某些基因座，当根据HLA或INS基因型对家庭进行分层时，对链接的支持大大增加，并且在分层亚组之间具有统计上的显着异质性。我们的数据支持确定T1DM表型的非HLA基因对于T1DM的存在以及HLA和非HLA基因座之间的相互作用。在分层亚组之间具有统计上的显着异质性。我们的数据支持确定T1DM表型的非HLA基因对于T1DM的存在以及HLA和非HLA基因座之间的相互作用。在分层亚组之间具有统计上的显着异质性。我们的数据支持确定T1DM表型的非HLA基因对于T1DM的存在以及HLA与非HLA基因座之间的相互作用。