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Using the longest significance run to estimate region-specific p-values in genetic association mapping studies
- Source :
- BMC Bioinformatics, Vol 9, Iss 1, p 246 (2008), BMC Bioinformatics
- Publication Year :
- 2008
- Publisher :
- BMC, 2008.
-
Abstract
- Background Association testing is a powerful tool for identifying disease susceptibility genes underlying complex diseases. Technological advances have yielded a dramatic increase in the density of available genetic markers, necessitating an increase in the number of association tests required for the analysis of disease susceptibility genes. As such, multiple-tests corrections have become a critical issue. However the conventional statistical corrections on locus-specific multiple tests usually result in lower power as the number of markers increases. Alternatively, we propose here the application of the longest significant run (LSR) method to estimate a region-specific p-value to provide an index for the most likely candidate region. Results An advantage of the LSR method relative to procedures based on genotypic data is that only p-value data are needed and hence can be applied extensively to different study designs. In this study the proposed LSR method was compared with commonly used methods such as Bonferroni's method and FDR controlling method. We found that while all methods provide good control over false positive rate, LSR has much better power and false discovery rate. In the authentic analysis on psoriasis and asthma disease data, the LSR method successfully identified important candidate regions and replicated the results of previous association studies. Conclusion The proposed LSR method provides an efficient exploratory tool for the analysis of sequences of dense genetic markers. Our results show that the LSR method has better power and lower false discovery rate comparing with the locus-specific multiple tests.
- Subjects :
- False discovery rate
Genetic Markers
Linkage disequilibrium
Biology
lcsh:Computer applications to medicine. Medical informatics
01 natural sciences
Biochemistry
Linkage Disequilibrium
010104 statistics & probability
03 medical and health sciences
symbols.namesake
Gene Frequency
Structural Biology
Predictive Value of Tests
Reference Values
Sequence Homology, Nucleic Acid
Statistics
medicine
Confidence Intervals
Humans
Psoriasis
Genetic Predisposition to Disease
Genetic Testing
0101 mathematics
Molecular Biology
lcsh:QH301-705.5
030304 developmental biology
Genetic association
Genetic testing
Genetics
0303 health sciences
Likelihood Functions
Chi-Square Distribution
medicine.diagnostic_test
Genome, Human
Applied Mathematics
Methodology Article
Uncertainty
Transmission disequilibrium test
DNA
Confidence interval
Computer Science Applications
Bonferroni correction
Logistic Models
Haplotypes
lcsh:Biology (General)
symbols
lcsh:R858-859.7
False positive rate
Subjects
Details
- Language :
- English
- ISSN :
- 14712105
- Volume :
- 9
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- BMC Bioinformatics
- Accession number :
- edsair.doi.dedup.....ef64f8a469f4a4117b594fb75125ce2a