Genetic Epidemiology 5 - What makes a good genetic association study?
Genetic Epidemiology 5 - What makes a good genetic association study?
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DOI：
10.1016/s0140-6736(05)67531-9
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发表时间：
2005-10-08
期刊：
影响因子：
168.9
通讯作者：
McCarthy, MI
中科院分区：
文献类型：
--
作者：
Hattersley, AT;McCarthy, MI
基因关联研究对于识别和描述多因素疾病易感性的基因组变异至关重要。然而，对初始关联发现进行有力的重复验证已被证明是困难的。这种不一致性在很大程度上可归因于研究设计、实施和解释的不足——样本量不足是一个主要问题。还有几个其他因素会影响任何特定关联研究的质量，恰当的样本招募策略、合理的变异选择、最小的基因分型错误、相关的数据分析以及有效的解释，对于得出可靠的研究结果都至关重要。重复验证在表明所识别的关联反映的是有趣的生物学过程而非方法学上的怪异之处方面起着至关重要的作用。对于任何特定关联的支持和反对证据的无偏观点而言，研究质量而非显著性值需要起主导作用。
Genetic association studies are central to efforts to identify and characterise genomic variants underlying susceptibility to multifactorial disease. However, obtaining robust replication of initial association findings has proved difficult. Much of this inconsistency can be attributed to inadequacies in study design, implementation, and interpretation-inadequately powered sample groups are a major concern. Several additional factors affect the quality of any given association study, with appropriate sample-recruitment strategy, logical variant selection, minimum genotyping error, relevant data analysis, and valid interpretation all essential to generation of robust findings. Replication has a vital role in showing that associations that are identified reflect interesting biological processes rather than methodological quirks. For an unbiased view of the evidence for and against any particular association, study quality, rather than significance value, needs to play the dominant part.