遺傳檢測公司23andMe聯(lián)合美國帕金森研究所（Parkinson's Institute）通過全基因組關(guān)聯(lián)研究（GWAS）,，鑒定出與帕金森氏癥相關(guān)的兩個新位點(diǎn),。該研究成果近日發(fā)表在《公共科學(xué)圖書館—遺傳學(xué)》（PLoS Genetics）上。
帕金森氏癥是一種慢性的中樞神經(jīng)系統(tǒng)退化性失調(diào),，它會損害患者的動作技能,、語言能力以及其他功能。歷史上有許多名人曾經(jīng)在晚年遭受到帕金森氏癥的困擾,，包括拳王阿里,、杜魯門、麥克阿瑟將軍,、凱瑟琳?赫本等,。它的病因至今仍不明，盡管有人認(rèn)為環(huán)境是帕金森氏癥的主要因素,，但近期的研究表明多個基因影響了疾病易感性,。
該研究小組的GWAS研究包括了3426名患有帕金森氏癥的個體，以及29624名未患有該病的對照個體,。利用定制的Illumina HumanHap 550+ 芯片,，研究人員對這些個體進(jìn)行基因分型。他們不僅驗(yàn)證了20個過去鑒定出的關(guān)聯(lián),，還檢測出兩個新的風(fēng)險(xiǎn)位點(diǎn),。這兩個SNP，一個落在2型溶酶體膜蛋白編碼基因SCARB2附近,，另一個則在SREBF1和RAI1基因附近,。
文章的第一作者，23andMe的科學(xué)家Chuong Do表示：“這些新的遺傳發(fā)現(xiàn)不僅很重要,，而且我們還表明,，23andMe采集的數(shù)據(jù)支持了新關(guān)聯(lián)的發(fā)現(xiàn)，以及已知關(guān)聯(lián)的重復(fù),。這項(xiàng)研究是一個嚴(yán)格的‘原理論證’研究,。”
基于目前的發(fā)現(xiàn)，研究小組預(yù)計(jì)至少1/4的帕金森氏癥風(fēng)險(xiǎn)與遺傳因素有關(guān),。下一步,，他們打算開展更多研究，來進(jìn)一步區(qū)分疾病的環(huán)境因素,。
與傳統(tǒng)研究不同,，這項(xiàng)研究的參與完全是通過網(wǎng)絡(luò)進(jìn)行的,。在一年半的時(shí)間內(nèi)，通過定向的郵件群發(fā),，招募了帕金森氏癥患者,。而對照是通過23andMe數(shù)據(jù)庫招募的。他們還通過一套在線問卷來確定病例的狀態(tài),。這些研究結(jié)果顯示了這種基于網(wǎng)絡(luò)的招募和數(shù)據(jù)采集方法對于了解疾病病因的能力,，并證明了自我報(bào)告的數(shù)據(jù)對于研究帕金森氏癥的能力和可靠性。
23andMe的總裁兼CEO Anne Wojcicki認(rèn)為：“我們相信,，這篇文章證明了我們將遺傳信息與基于網(wǎng)絡(luò)的數(shù)據(jù)結(jié)合來生成研究新發(fā)現(xiàn)的潛力,。這種方法有可能應(yīng)用在其他多種病例中。”（生物谷Bioon.com）
生物谷推薦原文出處：
PLoS Genetics doi:10.1371/journal.pgen.1002141.t001
Web-Based Genome-Wide Association Study Identifies Two Novel Loci and a Substantial Genetic Component for Parkinson's Disease
Chuong B. Do, Joyce Y. Tung, Elizabeth Dorfman, Amy K. Kiefer, Emily M. Drabant, Uta Francke1, Joanna L. Mountain, Samuel M. Goldman, Caroline M. Tanner, J. William Langston, Anne Wojcicki, Nicholas Eriksson
Although the causes of Parkinson's disease (PD) are thought to be primarily environmental, recent studies suggest that a number of genes influence susceptibility. Using targeted case recruitment and online survey instruments, we conducted the largest case-control genome-wide association study (GWAS) of PD based on a single collection of individuals to date (3,426 cases and 29,624 controls). We discovered two novel, genome-wide significant associations with PD–rs6812193 near SCARB2 (, ) and rs11868035 near SREBF1/RAI1 (, )—both replicated in an independent cohort. We also replicated 20 previously discovered genetic associations (including LRRK2, GBA, SNCA, MAPT, GAK, and the HLA region), providing support for our novel study design. Relying on a recently proposed method based on genome-wide sharing estimates between distantly related individuals, we estimated the heritability of PD to be at least 0.27. Finally, using sparse regression techniques, we constructed predictive models that account for 6%–7% of the total variance in liability and that suggest the presence of true associations just beyond genome-wide significance, as confirmed through both internal and external cross-validation. These results indicate a substantial, but by no means total, contribution of genetics underlying susceptibility to both early-onset and late-onset PD, suggesting that, despite the novel associations discovered here and elsewhere, the majority of the genetic component for Parkinson's disease remains to be discovered. Author Summary Top We conducted a large genome-wide association study (GWAS) of Parkinson's disease (PD) with over 3,400 cases and 29,000 controls (the largest single PD GWAS cohort to date). We report two novel genetic associations and replicate a total of twenty previously described associations, showing that there are now many solid genetic factors underlying PD. We also estimate that genetic factors explain at least one-fourth of the variation in PD liability, of which currently discovered factors only explain a small fraction (6%–7%). Together, these results expand the set of genetic factors discovered to date and imply that many more associations remain to be found. Unlike traditional studies, participation in this study took place completely online, using a collection of cases recruited primarily via PD mailing lists and controls derived from the customer base of the personal genetics company 23andMe. Our study thus illustrates the ability of web-based methods for enrollment and data collection to yield new scientific insights into the etiology of disease, and it demonstrates the power and reliability of self-reported data for studying the genetics of Parkinson's disease.
