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