Editorial: The Fruits of the Genomic Revolution.
Editorial: The Fruits of the Genomic Revolution.
复制标题
社论：基因组革命的成果。
DOI：
10.1158/1055-9965.epi-16-0914
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Sellers,ThomasA
中科院分区：
文献类型：
--
作者：
Rebbeck,TimothyR;Sellers,ThomasA
Decades of investment into genomic science has led to a revolution in our understanding of the architecture of the human genome, genomic variation, and the biological consequences of the genome on human health and disease. Before this scientific revolution, the genomic contribution to disease was widely thought to be a function of coding region variation in genes with functions linked to biologically plausible roles in the etiology of diseases of interest. Most disease susceptibility genes were identified through studies of families with Mendelian patterns of inheritance, where cosegregation of polymorphic DNA markers with disease would reveal the chromosomal location of the underlying susceptibility gene. The number of genetic loci identified by family-based studies numbered in the dozens to hundreds before the advent of the Human Genome Project and its descendants.Thanks to the technical and methodologic advancements that enabled genome-wide association study (GWAS), our understanding of the underlying genetics of most common diseases and traits has been fundamentally changed. As of October 2016, GWASs have identified at least 33,044 genetic associations, including at least 2,888 associations with cancer and cancer-related traits according to the NHGRI-EBI Catalog of published GWASs (https://www. ebi. ac. uk/gwas/home). Consistent with the" common disease common variant" hypothesis (1) that in part motivated the GWAS era, the effects of most loci identified are small, and the risk-associated alleles are relatively common. A large fraction of disease susceptibility loci is found in noncoding regions. Associations reported in putative regulatory regions and" gene deserts" are common. Most loci that have been identified do not lie in or near the candidate genes that were hypothesized to be involved in disease etiology. Many variants associated with common diseases and traits affect only one cancer, and there are relatively few genes that have pleiotropic effects across multiple diseases. Thus, with hindsight, it is now painfully clear why the candidate gene approach to identify common disease susceptibility loci was largely unsuccessful.
