IRCCS Casa Sollievo della Sofferenza, Mendel Laboratory, San Giovanni Rotondo, Italy.
Nutr Metab Cardiovasc Dis. 2012 Nov;22(11):929-36. doi: 10.1016/j.numecd.2012.04.010. Epub 2012 Jul 21.
Genome-wide association studies (GWAS) have identified several loci associated with many common, multifactorial diseases which have been recently used to market genetic testing directly to the consumers. We here addressed the clinical utility of such GWAS-derived genetic information in predicting type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) in diabetic patients. In addition, the development of new statistical approaches, novel technologies of genome sequencing and ethical, legal and social aspects related to genetic testing have been also addressed. Available data clearly show that, similarly to what reported for most common diseases, genetic testing offered today by commercial companies cannot be used as predicting tools for T2DM and CAD. Further studies taking into account the complex interaction between genes as well as between genetic and non-genetic factors, including age, obesity and glycemic control which seem to modify genetic effects on the risk of T2DM and CAD, might mitigate such negative conclusions. Also, addressing the role of relatively rare variants by next generation sequencing may help identify novel and strong genetic markers with an important role in genetic prediction. Finally, statistical tools concentrated on reclassifying patients might be a useful application of genetic information for predicting many common diseases. By now, prediction of such diseases, including those of interest for the clinical diabetologist, have to be pursued by using traditional clinical markers which perform well and are not costly.
全基因组关联研究(GWAS)已经确定了几个与许多常见的、多因素疾病相关的位点,这些位点最近被用于直接向消费者销售基因检测。我们在这里探讨了这些 GWAS 衍生的遗传信息在预测 2 型糖尿病(T2DM)和糖尿病患者的冠状动脉疾病(CAD)方面的临床应用。此外,还涉及了新的统计方法的发展、基因组测序的新技术以及与基因检测相关的伦理、法律和社会方面。现有数据清楚地表明,与大多数常见疾病的报告类似,商业公司目前提供的基因检测不能作为 T2DM 和 CAD 的预测工具。进一步的研究需要考虑基因之间以及遗传和非遗传因素之间的复杂相互作用,包括年龄、肥胖和血糖控制,这些因素似乎可以改变遗传因素对 T2DM 和 CAD 风险的影响,可能会减轻这些负面结论。此外,通过下一代测序来研究相对罕见的变异体,可能有助于识别在遗传预测中具有重要作用的新型和强遗传标记。最后,集中于重新分类患者的统计工具可能是遗传信息在预测许多常见疾病方面的一种有用应用。到目前为止,包括临床糖尿病学家感兴趣的疾病在内的这些疾病的预测仍需使用性能良好且成本低廉的传统临床标志物来进行。