https://scholars.lib.ntu.edu.tw/handle/123456789/521815
Title: | Improving power of genome-wide association studies with weighted false discovery rate control and prioritized subset analysis | Authors: | WAN-YU LIN WEN-CHUNG LEE |
Issue Date: | 2012 | Journal Volume: | 7 | Journal Issue: | 4 | Source: | PLoS ONE | Abstract: | The issue of large-scale testing has caught much attention with the advent of high-throughput technologies. In genomic studies, researchers are often confronted with a large number of tests. To make simultaneous inference for the many tests, the false discovery rate (FDR) control provides a practical balance between the number of true positives and the number of false positives. However, when few hypotheses are truly non-null, controlling the FDR may not provide additional advantages over controlling the family-wise error rate (e.g., the Bonferroni correction). To facilitate discoveries from a study, weighting tests according to prior information is a promising strategy. A 'weighted FDR control' (WEI) and a 'prioritized subset analysis' (PSA) have caught much attention. In this work, we compare the two weighting schemes with systematic simulation studies and demonstrate their use with a genome-wide association study (GWAS) on type 1 diabetes provided by the Wellcome Trust Case Control Consortium. The PSA and the WEI both can increase power when the prior is informative. With accurate and precise prioritization, the PSA can especially create substantial power improvements over the commonly-used whole-genome single-step FDR adjustment (i.e., the traditional un-weighted FDR control). When the prior is uninformative (true disease susceptibility regions are not prioritized), the power loss of the PSA and the WEI is almost negligible. However, a caution is that the overall FDR of the PSA can be slightly inflated if the prioritization is not accurate and precise. Our study highlights the merits of using information from mounting genetic studies, and provides insights to choose an appropriate weighting scheme to FDR control on GWAS. ? 2012 Lin, Lee. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84859502317&doi=10.1371%2fjournal.pone.0033716&partnerID=40&md5=7c7ef33d1d48d43b3579e8ee96777efd https://scholars.lib.ntu.edu.tw/handle/123456789/521815 |
ISSN: | 1932-6203 | DOI: | 10.1371/journal.pone.0033716 | SDG/Keyword: | accuracy; article; disease predisposition; gene frequency; genetic association; human; insulin dependent diabetes mellitus; prioritized subset analysis; simulation; single nucleotide polymorphism; statistical analysis; weighted false discovery rate control; biological model; case control study; comparative study; computer simulation; genetic predisposition; genetics; genomics; human genome; insulin dependent diabetes mellitus; laboratory diagnosis; methodology; Case-Control Studies; Computer Simulation; Diabetes Mellitus, Type 1; False Positive Reactions; Genetic Predisposition to Disease; Genome, Human; Genome-Wide Association Study; Genomics; Humans; Models, Genetic; Polymorphism, Single Nucleotide |
Appears in Collections: | 流行病學與預防醫學研究所 |
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