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Type I and type II errors for Multiple Simultaneous Hypothesis Testing

Gene-based bin-analysis of genome-wide association studied

author: Nicolas Omont, Serono, biotech and beyond

Description

With the improvement of genotyping technologies and the exponentially growing number of available markers, case-control genome-wide association studies promise to be a key tool for investigation of complex diseases. However new analytical methods have to be developed to face the problems induced by this data scale-up, such as statistical multiple testing, data quality control, biological interpretation and computational tractability. We present a novel method to analyze genome-wide association studies results. The algorithm is based on a Bayesian model that integrates genotyping errors and genomic structure dependencies. Probability values are assigned to genomic regions termed bins, which are defined from a gene-biased partitioning of the genome, and the false-discovery rate is estimated. We have applied this algorithm to data coming from three genome-wide association studies of Multiple Sclerosis. The method practically overcomes the scale-up problems and permits to identify new putative regions statistically associated with the disease.

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Slides
0:01 Bin analysis of genome-wide association study
1:14 Bin analysis of genome-wide study
1:40 Data – Biological Primer
1:43 Nucleus of a dividing cell (x1000)
2:03 Human male karyotype
2:24 DDNA stores information
2:54 Browse the genome!
3:11 Browse the genome!_1
3:37 Each cell hold 2 copies of DNA
4:37 Transmission and recombination
6:32 Haplotype blocks (HB)
7:52 Questions?
7:58 Data – association study
8:03 Genetic disease
8:57 Genetic disease_1
9:55 Association study: example
12:48 Association Study : cost problem
14:08 Single Nucleotide Polymorphism
16:25 Association study: example
16:47 Association study: example
18:21 The Serono association study
19:55 Questions?
20:05 Analysis
20:23 The ideal vision
21:19 Multiple testing problem_1
23:25 Method
25:23 Bin definition
26:22 Bin definition_1
28:33 Bin definition : Loss of power example
29:32 Bin definition : Loss of power example_1
30:46 Statistical test:
32:36 Estimation
38:12 Estimation: control of error
40:09 FDR estimation (no control)
41:55 Questions?
42:03 Results
42:05 Results: bins
44:02 P-value distribution
44:45 FDR: FDR vs p-value
49:23 Number of bins selected
51:45 FDR overestimation
53:31 Conclusion
59:12 Conclusion_1
60:05 Bin analysis of genome-wide association study

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