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全基因组关联研究中数量性状的选择性基因分型效能

Power of selective genotyping in genome-wide association studies of quantitative traits.

作者信息

Xing Chao, Xing Guan

机构信息

Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.

出版信息

BMC Proc. 2009 Dec 15;3 Suppl 7(Suppl 7):S23. doi: 10.1186/1753-6561-3-s7-s23.

Abstract

The selective genotyping approach in quantitative genetics means genotyping only individuals with extreme phenotypes. This approach is considered an efficient way to perform gene mapping, and can be applied in both linkage and association studies. Selective genotyping in association mapping of quantitative trait loci was proposed to increase the power of detecting rare alleles of large effect. However, using this approach, only common variants have been detected. Studies on selective genotyping have been limited to single-locus scenarios. In this study we aim to investigate the power of selective genotyping in a genome-wide association study scenario, and we specifically study the impact of minor allele frequency of variants on the power of this approach. We use the Genetic Analysis Workshop 16 rheumatoid arthritis whole-genome data from the North American Rheumatoid Arthritis Consortium. Two quantitative traits, anti-cyclic citrullinated peptide and rheumatoid factor immunoglobulin M, and one binary trait, rheumatoid arthritis affection status, are used in the analysis. The power of selective genotyping is explored as a function of three parameters: sampling proportion, minor allele frequency of single-nucleotide polymorphism, and test level. The results show that the selective genotyping approach is more efficient in detecting common variants than detecting rare variants, and it is efficient only when the level of declaring significance is not stringent. In summary, the selective genotyping approach is most suitable for detecting common variants in candidate gene-based studies.

摘要

数量遗传学中的选择性基因分型方法是指仅对具有极端表型的个体进行基因分型。这种方法被认为是进行基因定位的有效途径,可应用于连锁研究和关联研究。数量性状位点关联图谱中的选择性基因分型旨在提高检测具有大效应的罕见等位基因的效能。然而,使用这种方法仅检测到了常见变异。关于选择性基因分型的研究一直局限于单基因座情况。在本研究中,我们旨在调查全基因组关联研究情况下选择性基因分型的效能,并且我们专门研究变异的次要等位基因频率对该方法效能的影响。我们使用了来自北美类风湿关节炎联盟的遗传分析研讨会16的类风湿关节炎全基因组数据。分析中使用了两个数量性状,即抗环瓜氨酸肽和类风湿因子免疫球蛋白M,以及一个二元性状,即类风湿关节炎患病状态。选择性基因分型的效能作为三个参数的函数进行探索:抽样比例、单核苷酸多态性的次要等位基因频率和检验水平。结果表明,选择性基因分型方法在检测常见变异方面比检测罕见变异更有效,并且仅在显著性声明水平不严格时才有效。总之,选择性基因分型方法最适合在基于候选基因的研究中检测常见变异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55ca/2795920/d0e120ae4842/1753-6561-3-S7-S23-1.jpg

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