Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
Semin Nephrol. 2010 Mar;30(2):141-9. doi: 10.1016/j.semnephrol.2010.01.005.
Diabetic nephropathy is a classic complex trait, whose development in a given individual reflects contributions from multiple genes and whose expression is modulated by environmental factors. Numerous genetic strategies have been used to identify common disease risk loci and genes, including candidate gene analyses, linkage analysis, transmission disequilibrium testing (a family based association test to identify linkage between a genetic marker and a biological trait or disease), and admixture mapping (also referred to as mapping by admixture linkage disequilibrium). Choosing the best genetic strategy to identify susceptibility genes in a disease is dependent on knowing whether the disorder is monogenic (the result of one gene), oligogenic (the result of a few genes), or polygenic (the result of many genes). The likelihood of finding risk loci for a disease with a putative genetic contribution is in part owing to the disease recurrence risk ratio (the risk of expressing the disease phenotype in siblings of the proband divided by the risk observed in the general population), the genotypic risk ratio (the risk of expressing the phenotype if the gene is present divided by the risk if the gene is not present), the number of susceptibility genes, how the susceptibility genes interact, how much of the disease risk is contributed by environmental factors, and the disease penetrance (the likelihood that the phenotype will be expressed if the gene is present).
糖尿病肾病是一种典型的复杂性状，其在个体中的发生既反映了多个基因的贡献，又受到环境因素的调节。为了鉴定常见疾病风险基因座和基因，人们已经采用了多种遗传策略，包括候选基因分析、连锁分析、传递不平衡检验（一种基于家系的关联检验，用于鉴定遗传标记与生物性状或疾病之间的连锁），以及混合连锁分析（也称为混合连锁不平衡作图）。选择用于鉴定疾病易感性基因的最佳遗传策略取决于是否明确该疾病是单基因疾病（一种基因的结果）、寡基因疾病（少数几个基因的结果）还是多基因疾病（多个基因的结果）。对于具有潜在遗传贡献的疾病，发现风险基因座的可能性部分取决于疾病复发风险比（先证者的兄弟姐妹表达疾病表型的风险除以一般人群中观察到的风险）、基因型风险比（如果存在基因则表达表型的风险除以如果不存在基因则表达表型的风险）、易感性基因的数量、易感性基因的相互作用方式、环境因素对疾病风险的贡献程度以及疾病外显率（如果存在基因，则表达表型的可能性）。
