Department of Pathology, Leiden University Medical Center, Bldg.1, L1-Q, PO Box 9600, 2300 RC, Leiden, The Netherlands,
Clin Exp Nephrol. 2014 Apr;18(2):197-200. doi: 10.1007/s10157-013-0874-9. Epub 2013 Oct 16.
Diabetic nephropathy is a complex disease, caused by both environmental and genetic factors. As in most complex diseases, genetic association studies in diabetic nephropathy showed inconsistent results. In retrospect, studies with small sample sizes, given what are now known to be small odds ratios, were partially responsible for this poor replication record. Furthermore, the low prior probability in complex genetics and multiple testing played a role. Results become more consistent when one only considers those that were replicated. In a large meta-analysis study including only replicated associated genetic variants, 24 genetic variants in 16 genes were found to be associated with diabetic nephropathy. These genetic variants may provide novel biological insight. In particular, rare variants with a large effect found by hypothesis-free approaches (genome-wide association scans, next-generation sequencing) may open new avenues of discovery.
糖尿病肾病是一种复杂的疾病，由环境和遗传因素共同导致。与大多数复杂疾病一样，糖尿病肾病的遗传关联研究结果并不一致。回想起来，研究样本量小，而现在已知的优势比很小，这在一定程度上导致了这种较差的复制记录。此外，复杂遗传学和多次测试中的低先验概率也起了作用。当只考虑那些被复制的结果时，结果变得更加一致。在一项仅包括复制相关遗传变异的大型荟萃分析研究中，在 16 个基因中发现了 24 个与糖尿病肾病相关的遗传变异。这些遗传变异可能提供新的生物学见解。特别是通过无假设方法（全基因组关联扫描、下一代测序）发现的具有大效应的罕见变异可能开辟新的发现途径。
