5月29日，《歐洲人類遺傳學(xué)雜志》在線發(fā)表了上海生科院計(jì)算生物學(xué)研究所徐書華研究組的研究成果“A panel of ancestry informative markers to estimate and correct potential effects of population stratification in Han Chinese”,。該項(xiàng)工作針對(duì)復(fù)雜疾病關(guān)聯(lián)研究中由于群體遺傳結(jié)構(gòu)（或群體分層）導(dǎo)致假陽性結(jié)果的問題,，建立了一套識(shí)別漢族內(nèi)部遺傳結(jié)構(gòu)和控制復(fù)雜疾病關(guān)聯(lián)分析中群體分層的遺傳標(biāo)記,。這套標(biāo)記尤其適用于“post-GWAS”時(shí)代的基于候選基因策略的關(guān)聯(lián)研究,。
關(guān)聯(lián)分析是研究復(fù)雜疾病遺傳影響因素并建立“表型-基因型”聯(lián)系的重要手段,。基于人群樣本設(shè)計(jì)的關(guān)聯(lián)研究,，尤其是基于“病例-對(duì)照”設(shè)計(jì)的關(guān)聯(lián)研究,，經(jīng)常面臨的一個(gè)困難是人群遺傳結(jié)構(gòu)或群體分層作為一種嚴(yán)重的混雜因素導(dǎo)致的假陽性結(jié)果。漢族的歷史悠久,、起源復(fù)雜，加之幾千年的不同程度的基因交流和民族融合,，使得漢族遺傳成分極其復(fù)雜。在徐書華前期研究中,，已經(jīng)發(fā)現(xiàn)漢族人群內(nèi)部的遺傳結(jié)構(gòu)，并往往導(dǎo)致漢族人群關(guān)聯(lián)分析中的假陽性結(jié)果,。因此，如何識(shí)別并控制人群遺傳結(jié)構(gòu)對(duì)關(guān)聯(lián)分析結(jié)果的影響,，成為復(fù)雜疾病基因定位研究中不可回避的問題。
該項(xiàng)研究通過在5500例漢族個(gè)體的全基因組數(shù)據(jù)中篩選,，建立起可以高度識(shí)別漢族人群遺傳結(jié)構(gòu)的DNA標(biāo)記,，并進(jìn)一步通過實(shí)驗(yàn)數(shù)據(jù)和計(jì)算機(jī)仿真評(píng)估了這套標(biāo)記的效能。研究成果對(duì)今后在漢族人群中從事關(guān)聯(lián)分析的研究具有實(shí)際應(yīng)用價(jià)值,。通過這套標(biāo)記，直接依據(jù)DNA信息對(duì)遺傳結(jié)構(gòu)進(jìn)行識(shí)別,、對(duì)樣本進(jìn)行客觀分類和篩選，是關(guān)聯(lián)分析合理實(shí)驗(yàn)設(shè)計(jì)的前提,，也是保證關(guān)聯(lián)分析結(jié)果可靠性的必要條件,。
該工作由計(jì)算生物學(xué)所徐書華研究員與上海交通大學(xué)師詠勇教授以及復(fù)旦大學(xué)金力教授合作完成,。計(jì)算生物學(xué)所博士生秦鵬飛等實(shí)施了具體分析工作,。該研究工作得到了國家自然科學(xué)基金、中國科學(xué)院,、上海市科委,、德國馬普學(xué)會(huì)、香港王寬誠教育基金會(huì)等基金的資助,。(生物谷Bioon.com)
生物谷推薦英文摘要：
European Journal of Human Genetics doi:10.1038/ejhg.2013.111
A panel of ancestry informative markers to estimate and correct potential effects of population stratification in Han Chinese
Population stratification acts as a confounding factor in genetic association studies and may lead to false-positive or false-negative results. Previous studies have analyzed the genetic substructures in Han Chinese population, the largest ethnic group in the world comprising ~20% of the global human population. In this study, we examined 5540 Han Chinese individuals with about 1 million single-nucleotide polymorphisms (SNPs) and screened a panel of ancestry informative markers (AIMs) to facilitate the discerning and controlling of population structure in future association studies on Han Chinese. Based on genome-wide data, we first confirmed our previous observation of the north–south differentiation in Han Chinese population. Second, we developed a panel of 150 validated SNP AIMs to determine the northern or southern origin of each Han Chinese individual. We further evaluated the performance of our AIMs panel in association studies in simulation analysis. Our results showed that this AIMs panel had sufficient power to discern and control population stratification in Han Chinese, which could significantly reduce false-positive rates in both genome-wide association studies (GWAS) and candidate gene association studies (CGAS). We suggest this AIMs panel be genotyped and used to control and correct population stratification in the study design or data analysis of future association studies, especially in CGAS which is the most popular approach to validate previous reports on genetic associations of diseases in post-GWAS era.
