全基因组关联研究
计算生物学
基因组学
鉴定(生物学)
遗传关联
生物
功能基因组学
遗传学
候选基因
个性化医疗
基因组
基因
单核苷酸多态性
基因型
植物
作者
Helen Le-Niculescu,Sagar P. Patel,MA Bhat,Ronald Kuczenski,Stephen V. Faraone,Ming T. Tsuang,Francis J. McMahon,Nicholas J. Schork,John I. Nürnberger,A B Niculescu
摘要
Given the mounting convergent evidence implicating many more genes in complex disorders such as bipolar disorder than the small number identified unambiguously by the first-generation Genome-Wide Association studies (GWAS) to date, there is a strong need for improvements in methodology. One strategy is to include in the next generation GWAS larger numbers of subjects, and/or to pool independent studies into meta-analyses. We propose and provide proof of principle for the use of a complementary approach, convergent functional genomics (CFG), as a way of mining the existing GWAS datasets for signals that are there already, but did not reach significance using a genetics-only approach. With the CFG approach, the integration of genetics with genomics, of human and animal model data, and of multiple independent lines of evidence converging on the same genes offers a way of extracting signal from noise and prioritizing candidates. In essence our analysis is the most comprehensive integration of genetics and functional genomics to date in the field of bipolar disorder, yielding a series of novel (such as Klf12, Aldh1a1, A2bp1, Ak3l1, Rorb, Rora) and previously known (such as Bdnf, Arntl, Gsk3b, Disc1, Nrg1, Htr2a) candidate genes, blood biomarkers, as well as a comprehensive identification of pathways and mechanisms. These become prime targets for hypothesis driven follow-up studies, new drug development and personalized medicine approaches.
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