全基因組關(guān)聯(lián)研究（GWAS）發(fā)現(xiàn)了數(shù)百種與復(fù)雜人類(lèi)疾病相關(guān)的基因突變,，但這些突變大部分對(duì)增加患病風(fēng)險(xiǎn)的貢獻(xiàn)都非常小。遺傳性似乎有一大部分無(wú)法被檢測(cè)到,。人們對(duì)遺傳性中未能檢測(cè)到的這一部分提出以下可能的解釋?zhuān)河绊戄^小的大量變異體尚未發(fā)現(xiàn),；存在一些當(dāng)前的基因型分析技術(shù)無(wú)法檢測(cè)到的罕見(jiàn)的結(jié)構(gòu)變異或表觀(guān)遺傳變異,；以及存在難以檢測(cè)到的基因與基因之間和基因與環(huán)境之間的相互作用。
在一篇“Review”文章中,，Teri Manolio及其同事對(duì)最有可能將這些解釋和其他可能的解釋加以區(qū)分的研究策略進(jìn)行了分析,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature 461, 747-753 (8 October 2009) | doi:10.1038/nature08494
Finding the missing heritability of complex diseases
Teri A. Manolio1, Francis S. Collins2, Nancy J. Cox3, David B. Goldstein4, Lucia A. Hindorff5, David J. Hunter6, Mark I. McCarthy7, Erin M. Ramos5, Lon R. Cardon8, Aravinda Chakravarti9, Judy H. Cho10, Alan E. Guttmacher1, Augustine Kong11, Leonid Kruglyak12, Elaine Mardis13, Charles N. Rotimi14, Montgomery Slatkin15, David Valle9, Alice S. Whittemore16, Michael Boehnke17, Andrew G. Clark18, Evan E. Eichler19, Greg Gibson20, Jonathan L. Haines21, Trudy F. C. Mackay22, Steven A. McCarroll23 & Peter M. Visscher24
Genome-wide association studies have identified hundreds of genetic variants associated with complex human diseases and traits, and have provided valuable insights into their genetic architecture. Most variants identified so far confer relatively small increments in risk, and explain only a small proportion of familial clustering, leading many to question how the remaining, 'missing' heritability can be explained. Here we examine potential sources of missing heritability and propose research strategies, including and extending beyond current genome-wide association approaches, to illuminate the genetics of complex diseases and enhance its potential to enable effective disease prevention or treatment.
