摘要
关联研究广泛应用于阐述心血管疾病、2型糖尿病、原发性高血压和肥胖等人类复杂疾病的遗传学基础。文中就关联研究中混杂的识别与控制、候选基因的选择、中间表型的应用、单体型分析方法的应用 ,以及结果的判定等问题进行了讨论。人群分层是关联研究混杂的主要来源之一。选择患者亲属做对照、基因组对照和选择遗传背景较为一致的隔离人群都可以减少混杂。候选基因的选择可以基于与疾病间的生物学联系或是该基因与疾病某已知相关基因的同源性。适当的应用中间表型和单体型分析方法可以增加关联研究有意义发现的机会。本文认为 ,优化研究设计、足够的样本含量、正确选择对照 ,结合先进的数据分析方法 ,关联研究必将为困扰人类的常见疾病的易感性研究发挥更大的作用。
Association study is widely used in elucidating genetic basis of complex diseases such as cardiovascular diseases,type 2 diabetes,essential hypertension and obesity.Some issues were discussed in the review,which include defining and controlling of confounding effects,selection of candidate genes and single nucleotide polymorphisms (SNPs),application of intermediate phenotype and haplotype analyses as well as judgement of the result in association studies.Population stratification is one of the major causes of confounding in association studies.It could be reduced by selecting relatives of affected patients as control,genome control and by using isolated populations which have higher homogeneity in genetic background.A candidate gene could be selected because of its’biological association with some disease or being congenerous to a known gene related to the disease.Appropriate application of intermediate phenotype of diseases and haplotype analyses may increase the opportunity to obtain meaningful findings in association studies.An optimal study design,sufficient sample size and proper controls,in conjunction of modern statistic analyses,association analyses would exert its effect on studies on susceptibility of human common diseases.
