Genome wide association for addiction: replicated results and comparisons of two analytic approaches.

<h4>Background</h4>Vulnerabilities to dependence on addictive substances are substantially heritable complex disorders whose underlying genetic architecture is likely to be polygenic, with modest contributions from variants in many individual genes. "Nontemplate" genome wide as...

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Autores principales:	Tomas Drgon, Ping-Wu Zhang, Catherine Johnson, Donna Walther, Judith Hess, Michelle Nino, George R Uhl
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ebe9c07740c54510988fa43695fa6a07
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spelling	oai:doaj.org-article:ebe9c07740c54510988fa43695fa6a072021-11-25T06:26:30ZGenome wide association for addiction: replicated results and comparisons of two analytic approaches.1932-620310.1371/journal.pone.0008832https://doaj.org/article/ebe9c07740c54510988fa43695fa6a072010-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20098672/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Vulnerabilities to dependence on addictive substances are substantially heritable complex disorders whose underlying genetic architecture is likely to be polygenic, with modest contributions from variants in many individual genes. "Nontemplate" genome wide association (GWA) approaches can identity groups of chromosomal regions and genes that, taken together, are much more likely to contain allelic variants that alter vulnerability to substance dependence than expected by chance.<h4>Methodology/principal findings</h4>We report pooled "nontemplate" genome-wide association studies of two independent samples of substance dependent vs control research volunteers (n = 1620), one European-American and the other African-American using 1 million SNP (single nucleotide polymorphism) Affymetrix genotyping arrays. We assess convergence between results from these two samples using two related methods that seek clustering of nominally-positive results and assess significance levels with Monte Carlo and permutation approaches. Both "converge then cluster" and "cluster then converge" analyses document convergence between the results obtained from these two independent datasets in ways that are virtually never found by chance. The genes identified in this fashion are also identified by individually-genotyped dbGAP data that compare allele frequencies in cocaine dependent vs control individuals.<h4>Conclusions/significance</h4>These overlapping results identify small chromosomal regions that are also identified by genome wide data from studies of other relevant samples to extents much greater than chance. These chromosomal regions contain more genes related to "cell adhesion" processes than expected by chance. They also contain a number of genes that encode potential targets for anti-addiction pharmacotherapeutics. "Nontemplate" GWA approaches that seek chromosomal regions in which nominally-positive associations are found in multiple independent samples are likely to complement classical, "template" GWA approaches in which "genome wide" levels of significance are sought for SNP data from single case vs control comparisons.Tomas DrgonPing-Wu ZhangCatherine JohnsonDonna WaltherJudith HessMichelle NinoGeorge R UhlPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 1, p e8832 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tomas Drgon Ping-Wu Zhang Catherine Johnson Donna Walther Judith Hess Michelle Nino George R Uhl Genome wide association for addiction: replicated results and comparisons of two analytic approaches.
description	<h4>Background</h4>Vulnerabilities to dependence on addictive substances are substantially heritable complex disorders whose underlying genetic architecture is likely to be polygenic, with modest contributions from variants in many individual genes. "Nontemplate" genome wide association (GWA) approaches can identity groups of chromosomal regions and genes that, taken together, are much more likely to contain allelic variants that alter vulnerability to substance dependence than expected by chance.<h4>Methodology/principal findings</h4>We report pooled "nontemplate" genome-wide association studies of two independent samples of substance dependent vs control research volunteers (n = 1620), one European-American and the other African-American using 1 million SNP (single nucleotide polymorphism) Affymetrix genotyping arrays. We assess convergence between results from these two samples using two related methods that seek clustering of nominally-positive results and assess significance levels with Monte Carlo and permutation approaches. Both "converge then cluster" and "cluster then converge" analyses document convergence between the results obtained from these two independent datasets in ways that are virtually never found by chance. The genes identified in this fashion are also identified by individually-genotyped dbGAP data that compare allele frequencies in cocaine dependent vs control individuals.<h4>Conclusions/significance</h4>These overlapping results identify small chromosomal regions that are also identified by genome wide data from studies of other relevant samples to extents much greater than chance. These chromosomal regions contain more genes related to "cell adhesion" processes than expected by chance. They also contain a number of genes that encode potential targets for anti-addiction pharmacotherapeutics. "Nontemplate" GWA approaches that seek chromosomal regions in which nominally-positive associations are found in multiple independent samples are likely to complement classical, "template" GWA approaches in which "genome wide" levels of significance are sought for SNP data from single case vs control comparisons.
format	article
author	Tomas Drgon Ping-Wu Zhang Catherine Johnson Donna Walther Judith Hess Michelle Nino George R Uhl
author_facet	Tomas Drgon Ping-Wu Zhang Catherine Johnson Donna Walther Judith Hess Michelle Nino George R Uhl
author_sort	Tomas Drgon
title	Genome wide association for addiction: replicated results and comparisons of two analytic approaches.
title_short	Genome wide association for addiction: replicated results and comparisons of two analytic approaches.
title_full	Genome wide association for addiction: replicated results and comparisons of two analytic approaches.
title_fullStr	Genome wide association for addiction: replicated results and comparisons of two analytic approaches.
title_full_unstemmed	Genome wide association for addiction: replicated results and comparisons of two analytic approaches.
title_sort	genome wide association for addiction: replicated results and comparisons of two analytic approaches.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/ebe9c07740c54510988fa43695fa6a07
work_keys_str_mv	AT tomasdrgon genomewideassociationforaddictionreplicatedresultsandcomparisonsoftwoanalyticapproaches AT pingwuzhang genomewideassociationforaddictionreplicatedresultsandcomparisonsoftwoanalyticapproaches AT catherinejohnson genomewideassociationforaddictionreplicatedresultsandcomparisonsoftwoanalyticapproaches AT donnawalther genomewideassociationforaddictionreplicatedresultsandcomparisonsoftwoanalyticapproaches AT judithhess genomewideassociationforaddictionreplicatedresultsandcomparisonsoftwoanalyticapproaches AT michellenino genomewideassociationforaddictionreplicatedresultsandcomparisonsoftwoanalyticapproaches AT georgeruhl genomewideassociationforaddictionreplicatedresultsandcomparisonsoftwoanalyticapproaches
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Genome wide association for addiction: replicated results and comparisons of two analytic approaches.

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