genome-wide association study heterogeneous cohort homogenization via subject weight knock-down全基因组关联研究异构群体同质化通过重量压倒一切的主题.pdfVIP

Genome-Wide Association Study Heterogeneous Cohort Homogenization via Subject Weight Knock-Down ´ 1,2,3 4 5 5 4 Andre X. C. N. Valente *, Joseph Zischkau , Joo Heon Shin , Yuan Gao , Abhijit Sarkar 1 Systems Biology Group, Biocant – Biotechnology Innovation Center, Cantanhede, Portugal, 2 Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal, 3 Center for the Study of Biocomplexity, Virginia Commonwealth University, Richmond, Virginia, United States of America, 4 Physics Department and Vitreous State Laboratory, Catholic University of America, Washington DC, United States of America, 5 Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, United States of America Abstract Population structure can be a source of both false-positive and false-negative findings in a genome-wide association study. This article proposes an approach that helps to reduce the false-positives. It consists of homogenizing the diseased/healthy phenotype ratio across the cohort, by decreasing the statistical weight of selected individuals. After homogenization, the cohort is statistically handled as if originating from a single well-mixed population. The method was applied to homogenize a Parkinson’s disease genome-wide association study cohort. Citation: Valente AXCN, Zischkau J, Shin JH, Gao Y, Sarkar A (2012) Genome-Wide Association Study Heterogeneous Cohort Homogenization via Subject Weight Knock-Down. PLoS ONE 7(10): e48653. doi:10.1371/journal.pone.0048653 Editor: Frank Emmert-Streib, Queen’s University Belfast, United Kingdom Received March 13, 2012; Accepted September 28, 2012; Published October 29, 2012 Copyright: 2012 Valente et al. This is an open-access article distributed under the terms of