Author
Listed:
- Mara M Abad-Grau
- Nuria Medina-Medina
- Rosana Montes-Soldado
- Fuencisla Matesanz
- Vineet Bafna
Abstract
Multimarker Transmission/Disequilibrium Tests (TDTs) are very robust association tests to population admixture and structure which may be used to identify susceptibility loci in genome-wide association studies. Multimarker TDTs using several markers may increase power by capturing high-degree associations. However, there is also a risk of spurious associations and power reduction due to the increase in degrees of freedom. In this study we show that associations found by tests built on simple null hypotheses are highly reproducible in a second independent data set regardless the number of markers. As a test exhibiting this feature to its maximum, we introduce the multimarker -Groups TDT (), a test which under the hypothesis of no linkage, asymptotically follows a distribution with degree of freedom regardless the number of markers. The statistic requires the division of parental haplotypes into two groups: disease susceptibility and disease protective haplotype groups. We assessed the test behavior by performing an extensive simulation study as well as a real-data study using several data sets of two complex diseases. We show that test is highly efficient and it achieves the highest power among all the tests used, even when the null hypothesis is tested in a second independent data set. Therefore, turns out to be a very promising multimarker TDT to perform genome-wide searches for disease susceptibility loci that may be used as a preprocessing step in the construction of more accurate genetic models to predict individual susceptibility to complex diseases.
Suggested Citation
Mara M Abad-Grau & Nuria Medina-Medina & Rosana Montes-Soldado & Fuencisla Matesanz & Vineet Bafna, 2012.
"Sample Reproducibility of Genetic Association Using Different Multimarker TDTs in Genome-Wide Association Studies: Characterization and a New Approach,"
PLOS ONE, Public Library of Science, vol. 7(2), pages 1-14, February.
Handle:
RePEc:plo:pone00:0029613
DOI: 10.1371/journal.pone.0029613
Download full text from publisher
Corrections
All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:plo:pone00:0029613. See general information about how to correct material in RePEc.
If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.
We have no bibliographic references for this item. You can help adding them by using this form .
If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.
For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: plosone (email available below). General contact details of provider: https://journals.plos.org/plosone/ .
Please note that corrections may take a couple of weeks to filter through
the various RePEc services.