Sample reproducibility of genetic association using different multimarker TDTs in genome-wide association studies: characterization and a new approach.

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 associ...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Mara M Abad-Grau, Nuria Medina-Medina, Rosana Montes-Soldado, Fuencisla Matesanz, Vineet Bafna
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2012
Materias:
R
Q
Acceso en línea:https://doaj.org/article/f312c6bdea3947499321b410ecd71dae
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:f312c6bdea3947499321b410ecd71dae
record_format dspace
spelling oai:doaj.org-article:f312c6bdea3947499321b410ecd71dae2021-11-18T07:27:50ZSample reproducibility of genetic association using different multimarker TDTs in genome-wide association studies: characterization and a new approach.1932-620310.1371/journal.pone.0029613https://doaj.org/article/f312c6bdea3947499321b410ecd71dae2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22363405/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Multimarker 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 2-Groups TDT (mTDT(2G)), a test which under the hypothesis of no linkage, asymptotically follows a χ2 distribution with 1 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 mTDT(2G) 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, mTDT(2G) 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.Mara M Abad-GrauNuria Medina-MedinaRosana Montes-SoldadoFuencisla MatesanzVineet BafnaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 2, p e29613 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Mara M Abad-Grau
Nuria Medina-Medina
Rosana Montes-Soldado
Fuencisla Matesanz
Vineet Bafna
Sample reproducibility of genetic association using different multimarker TDTs in genome-wide association studies: characterization and a new approach.
description 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 2-Groups TDT (mTDT(2G)), a test which under the hypothesis of no linkage, asymptotically follows a χ2 distribution with 1 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 mTDT(2G) 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, mTDT(2G) 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.
format article
author Mara M Abad-Grau
Nuria Medina-Medina
Rosana Montes-Soldado
Fuencisla Matesanz
Vineet Bafna
author_facet Mara M Abad-Grau
Nuria Medina-Medina
Rosana Montes-Soldado
Fuencisla Matesanz
Vineet Bafna
author_sort Mara M Abad-Grau
title Sample reproducibility of genetic association using different multimarker TDTs in genome-wide association studies: characterization and a new approach.
title_short Sample reproducibility of genetic association using different multimarker TDTs in genome-wide association studies: characterization and a new approach.
title_full Sample reproducibility of genetic association using different multimarker TDTs in genome-wide association studies: characterization and a new approach.
title_fullStr Sample reproducibility of genetic association using different multimarker TDTs in genome-wide association studies: characterization and a new approach.
title_full_unstemmed Sample reproducibility of genetic association using different multimarker TDTs in genome-wide association studies: characterization and a new approach.
title_sort sample reproducibility of genetic association using different multimarker tdts in genome-wide association studies: characterization and a new approach.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/f312c6bdea3947499321b410ecd71dae
work_keys_str_mv AT maramabadgrau samplereproducibilityofgeneticassociationusingdifferentmultimarkertdtsingenomewideassociationstudiescharacterizationandanewapproach
AT nuriamedinamedina samplereproducibilityofgeneticassociationusingdifferentmultimarkertdtsingenomewideassociationstudiescharacterizationandanewapproach
AT rosanamontessoldado samplereproducibilityofgeneticassociationusingdifferentmultimarkertdtsingenomewideassociationstudiescharacterizationandanewapproach
AT fuencislamatesanz samplereproducibilityofgeneticassociationusingdifferentmultimarkertdtsingenomewideassociationstudiescharacterizationandanewapproach
AT vineetbafna samplereproducibilityofgeneticassociationusingdifferentmultimarkertdtsingenomewideassociationstudiescharacterizationandanewapproach
_version_ 1718423447677173760