Joint ancestry and association testing in admixed individuals.

For samples of admixed individuals, it is possible to test for both ancestry effects via admixture mapping and genotype effects via association mapping. Here, we describe a joint test called BMIX that combines admixture and association statistics at single markers. We first perform high-density admi...

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Autores principales:	Daniel Shriner, Adebowale Adeyemo, Charles N Rotimi
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/88d7c791fcf04cf9aa8500c0a2e2838f
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spelling	oai:doaj.org-article:88d7c791fcf04cf9aa8500c0a2e2838f2021-11-18T05:51:42ZJoint ancestry and association testing in admixed individuals.1553-734X1553-735810.1371/journal.pcbi.1002325https://doaj.org/article/88d7c791fcf04cf9aa8500c0a2e2838f2011-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22216000/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358For samples of admixed individuals, it is possible to test for both ancestry effects via admixture mapping and genotype effects via association mapping. Here, we describe a joint test called BMIX that combines admixture and association statistics at single markers. We first perform high-density admixture mapping using local ancestry. We then perform association mapping using stratified regression, wherein for each marker genotypes are stratified by local ancestry. In both stages, we use generalized linear models, providing the advantage that the joint test can be used with any phenotype distribution with an appropriate link function. To define the alternative densities for admixture mapping and association mapping, we describe a method based on autocorrelation to empirically estimate the testing burdens of admixture mapping and association mapping. We then describe a joint test that uses the posterior probabilities from admixture mapping as prior probabilities for association mapping, capitalizing on the reduced testing burden of admixture mapping relative to association mapping. By simulation, we show that BMIX is potentially orders-of-magnitude more powerful than the MIX score, which is currently the most powerful frequentist joint test. We illustrate the gain in power through analysis of fasting plasma glucose among 922 unrelated, non-diabetic, admixed African Americans from the Howard University Family Study. We detected loci at 1q24 and 6q26 as genome-wide significant via admixture mapping; both loci have been independently reported from linkage analysis. Using the association data, we resolved the 1q24 signal into two regions. One region, upstream of the gene FAM78B, contains three binding sites for the transcription factor PPARG and two binding sites for HNF1A, both previously implicated in the pathology of type 2 diabetes. The fact that both loci showed ancestry effects may provide novel insight into the genetic architecture of fasting plasma glucose in individuals of African ancestry.Daniel ShrinerAdebowale AdeyemoCharles N RotimiPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 7, Iss 12, p e1002325 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Daniel Shriner Adebowale Adeyemo Charles N Rotimi Joint ancestry and association testing in admixed individuals.
description	For samples of admixed individuals, it is possible to test for both ancestry effects via admixture mapping and genotype effects via association mapping. Here, we describe a joint test called BMIX that combines admixture and association statistics at single markers. We first perform high-density admixture mapping using local ancestry. We then perform association mapping using stratified regression, wherein for each marker genotypes are stratified by local ancestry. In both stages, we use generalized linear models, providing the advantage that the joint test can be used with any phenotype distribution with an appropriate link function. To define the alternative densities for admixture mapping and association mapping, we describe a method based on autocorrelation to empirically estimate the testing burdens of admixture mapping and association mapping. We then describe a joint test that uses the posterior probabilities from admixture mapping as prior probabilities for association mapping, capitalizing on the reduced testing burden of admixture mapping relative to association mapping. By simulation, we show that BMIX is potentially orders-of-magnitude more powerful than the MIX score, which is currently the most powerful frequentist joint test. We illustrate the gain in power through analysis of fasting plasma glucose among 922 unrelated, non-diabetic, admixed African Americans from the Howard University Family Study. We detected loci at 1q24 and 6q26 as genome-wide significant via admixture mapping; both loci have been independently reported from linkage analysis. Using the association data, we resolved the 1q24 signal into two regions. One region, upstream of the gene FAM78B, contains three binding sites for the transcription factor PPARG and two binding sites for HNF1A, both previously implicated in the pathology of type 2 diabetes. The fact that both loci showed ancestry effects may provide novel insight into the genetic architecture of fasting plasma glucose in individuals of African ancestry.
format	article
author	Daniel Shriner Adebowale Adeyemo Charles N Rotimi
author_facet	Daniel Shriner Adebowale Adeyemo Charles N Rotimi
author_sort	Daniel Shriner
title	Joint ancestry and association testing in admixed individuals.
title_short	Joint ancestry and association testing in admixed individuals.
title_full	Joint ancestry and association testing in admixed individuals.
title_fullStr	Joint ancestry and association testing in admixed individuals.
title_full_unstemmed	Joint ancestry and association testing in admixed individuals.
title_sort	joint ancestry and association testing in admixed individuals.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/88d7c791fcf04cf9aa8500c0a2e2838f
work_keys_str_mv	AT danielshriner jointancestryandassociationtestinginadmixedindividuals AT adebowaleadeyemo jointancestryandassociationtestinginadmixedindividuals AT charlesnrotimi jointancestryandassociationtestinginadmixedindividuals
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Joint ancestry and association testing in admixed individuals.

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