Beyond genome-wide association studies: genetic heterogeneity and individual predisposition to cancer.
Beyond genome-wide association studies: genetic heterogeneity and individual predisposition to cancer.
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DOI：
10.1016/j.tig.2009.12.008
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发表时间：
2010-03
影响因子：
11.4
通讯作者：
Dragani, Tommaso A.
中科院分区：
文献类型：
--
作者：
Galvan, Antonella;Ioannidis, John P. A.;Dragani, Tommaso A.
使用基于人群的设计的全基因组关联研究（GWAS）已经确定了许多与一系列复杂疾病（包括癌症）风险相关的遗传位点；然而，每个位点的影响都非常小，并且大多数遗传性仍然无法解释。基于家族的谱系研究还表明，与癌症风险增加相关的暂定位点，通常具有谱系特异性。然而，人口研究结果与家庭研究结果之间的比较显示出很少的一致性。对这种未知的癌症遗传“暗物质”的解释包括表型确定问题、有限的功效、基因-基因和基因-环境相互作用、群体异质性、亲本特异性效应、罕见和未经探索的变异。其中许多原因都集中在遗传异质性的概念上，这可能涉及数百种遗传变异在调节癌症风险方面的作用。剖析暗物质是一项具有挑战性的任务。可以从人口关联和谱系研究中获得进一步的见解。
Genome-wide association studies (GWAS) using population-based designs have identified many genetic loci associated with risk of a range of complex diseases including cancer; however, each locus exerts a very small effect and most heritability remains unexplained. Family-based pedigree studies have also suggested tentative loci linked to increased cancer risk, often characterized by pedigree-specificity. However, a comparison between the results of population-and those of family-based studies shows little concordance. Explanations for this unidentified genetic ‘dark matter’ of cancer include phenotype ascertainment issues, limited power, gene-gene and gene-environment interactions, population heterogeneity, parent-of-origin-specific effects, rare and unexplored variants. Many of these reasons converge towards the concept of genetic heterogeneity that might implicate hundreds of genetic variants in regulating cancer risk. Dissecting the dark matter is a challenging task. Further insights can be gained from both population association and pedigree studies.
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通讯作者：
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