Epigenome-wide association studies for common human diseases.

Epigenome-wide association studies for common human diseases.
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DOI:
10.1038/nrg3000
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发表时间:
2011-07-12
期刊:
Nature reviews. Genetics
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尽管全基因组关联研究(GWAS)在确定与常见疾病相关的基因座方面取得了成功,但仍有相当一部分因果关系无法解释。基因组技术的最新进展使我们能够启动人类疾病相关表观遗传变异的大规模研究,特别是DNA甲基化(DNAm)的变异。这种表观基因组关联研究(EWAS)提供了新的机会,但也创造了GWAS中没有遇到的新挑战。我们讨论了EWAS研究设计、队列和样本选择、统计学显著性和把握度、混杂因素和随访研究。我们还讨论了如何整合EWAS与GWAS可以帮助解剖复杂的GWAS单倍型的功能分析。
Despite the success of genome-wide association studies (GWAS) in identifying loci associated with common diseases, a significant proportion of the causality remains unexplained. Recent advances in genomic technologies have placed us in a position to initiate large-scale studies of human disease-associated epigenetic variation, specifically variation in DNA methylation (DNAm). Such Epigenome-Wide Association Studies (EWAS) present novel opportunities but also create new challenges that are not encountered in GWAS. We discuss EWAS study design, cohort and sample selections, statistical significance and power, confounding factors, and follow-up studies. We also discuss how integration of EWAS with GWAS can help to dissect complex GWAS haplotypes for functional analysis.
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