Patterns of Cis Regulatory Variation in Diverse Human Populations
Publication Date
April 19, 2012
Journal
PLOS Genetics
Authors
Barbara E. Stranger, Stephen B. Montgomery, Antigone S. Dimas, Leopold Parts, et al
Volume
8
Issue
4
Pages
e1002639
DOI
http://doi.org/10.1371/journal.pgen.1002639
Publisher URL
http://journals.plos.org/plosgenetics/article?id=10.1371%2Fjournal.pgen.1002639
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/22532805
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3330104
Europe PMC
http://europepmc.org/abstract/MED/22532805
Web of Science
000303441800020
Scopus
84860596557
Mendeley
http://www.mendeley.com/research/patterns-cis-regulatory-variation-diverse-human-populations
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Mendeley | Further Information

{"title"=>"Patterns of Cis regulatory variation in diverse human populations", "type"=>"journal", "authors"=>[{"first_name"=>"Barbara E.", "last_name"=>"Stranger", "scopus_author_id"=>"6507901873"}, {"first_name"=>"Stephen B.", "last_name"=>"Montgomery", "scopus_author_id"=>"8708455800"}, {"first_name"=>"Antigone S.", "last_name"=>"Dimas", "scopus_author_id"=>"16506100400"}, {"first_name"=>"Leopold", "last_name"=>"Parts", "scopus_author_id"=>"57195956429"}, {"first_name"=>"Oliver", "last_name"=>"Stegle", "scopus_author_id"=>"57194781099"}, {"first_name"=>"Catherine E.", "last_name"=>"Ingle", "scopus_author_id"=>"15753810100"}, {"first_name"=>"Magda", "last_name"=>"Sekowska", "scopus_author_id"=>"35076528600"}, {"first_name"=>"George Davey", "last_name"=>"Smith", "scopus_author_id"=>"35354080500"}, {"first_name"=>"David", "last_name"=>"Evans", "scopus_author_id"=>"7601570762"}, {"first_name"=>"Maria", "last_name"=>"Gutierrez-Arcelus", "scopus_author_id"=>"23995220200"}, {"first_name"=>"Alkes", "last_name"=>"Price", "scopus_author_id"=>"57199322743"}, {"first_name"=>"Towfique", "last_name"=>"Raj", "scopus_author_id"=>"39561540100"}, {"first_name"=>"James", "last_name"=>"Nisbett", "scopus_author_id"=>"57189157475"}, {"first_name"=>"Alexandra C.", "last_name"=>"Nica", "scopus_author_id"=>"57189985825"}, {"first_name"=>"Claude", "last_name"=>"Beazley", "scopus_author_id"=>"23569388000"}, {"first_name"=>"Richard", "last_name"=>"Durbin", "scopus_author_id"=>"7102868950"}, {"first_name"=>"Panos", "last_name"=>"Deloukas", "scopus_author_id"=>"7003287098"}, {"first_name"=>"Emmanouil T.", "last_name"=>"Dermitzakis", "scopus_author_id"=>"35354477100"}], "year"=>2012, "source"=>"PLoS Genetics", "identifiers"=>{"scopus"=>"2-s2.0-84860596557", "doi"=>"10.1371/journal.pgen.1002639", "sgr"=>"84860596557", "isbn"=>"1553-7404", "pmid"=>"22532805", "issn"=>"15537390", "pui"=>"364739017"}, "id"=>"a3c52ac2-0f28-3e23-bac5-dd7ea6f787af", "abstract"=>"The genetic basis of gene expression variation has long been studied with the aim to understand the landscape of regulatory variants, but also more recently to assist in the interpretation and elucidation of disease signals. To date, many studies have looked in specific tissues and population-based samples, but there has been limited assessment of the degree of inter-population variability in regulatory variation. We analyzed genome-wide gene expression in lymphoblastoid cell lines from a total of 726 individuals from 8 global populations from the HapMap3 project and correlated gene expression levels with HapMap3 SNPs located in cis to the genes. We describe the influence of ancestry on gene expression levels within and between these diverse human populations and uncover a non-negligible impact on global patterns of gene expression. We further dissect the specific functional pathways differentiated between populations. We also identify 5,691 expression quantitative trait loci (eQTLs) after controlling for both non-genetic factors and population admixture and observe that half of the cis-eQTLs are replicated in one or more of the populations. We highlight patterns of eQTL-sharing between populations, which are partially determined by population genetic relatedness, and discover significant sharing of eQTL effects between Asians, European-admixed, and African subpopulations. Specifically, we observe that both the effect size and the direction of effect for eQTLs are highly conserved across populations. We observe an increasing proximity of eQTLs toward the transcription start site as sharing of eQTLs among populations increases, highlighting that variants close to TSS have stronger effects and therefore are more likely to be detected across a wider panel of populations. Together these results offer a unique picture and resource of the degree of differentiation among human populations in functional regulatory variation and provide an estimate for the transferability of complex trait variants across populations", "link"=>"http://www.mendeley.com/research/patterns-cis-regulatory-variation-diverse-human-populations", "reader_count"=>339, "reader_count_by_academic_status"=>{"Unspecified"=>5, "Professor > Associate Professor"=>22, "Researcher"=>108, "Student > Doctoral Student"=>11, "Student > Ph. D. Student"=>122, "Student > Postgraduate"=>7, "Other"=>10, "Student > Master"=>23, "Student > Bachelor"=>12, "Lecturer"=>2, "Professor"=>17}, "reader_count_by_user_role"=>{"Unspecified"=>5, "Professor > Associate Professor"=>22, "Researcher"=>108, "Student > Doctoral Student"=>11, "Student > Ph. D. 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Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/650814"], "description"=>"<p><i>Cis</i>- associations detected with Spearman Rank Correlation analysis of normalized and PCA-corrected expression data.</p>", "links"=>[], "tags"=>["associations", "spearman", "normalized", "pca-corrected"], "article_id"=>321292, "categories"=>["Genetics"], "users"=>["Barbara E. Stranger", "Stephen B. Montgomery", "Antigone S. Dimas", "Leopold Parts", "Oliver Stegle", "Catherine E. Ingle", "Magda Sekowska", "George Davey Smith", "David Evans", "Maria Gutierrez-Arcelus", "Alkes Price", "Towfique Raj", "James Nisbett", "Alexandra C. Nica", "Claude Beazley", "Richard Durbin", "Panos Deloukas", "Emmanouil T. Dermitzakis"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002639.t001", "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cis_associations_detected_with_Spearman_Rank_Correlation_analysis_of_normalized_and_PCA_corrected_expression_data_/321292", "title"=>"<i>Cis</i>- associations detected with Spearman Rank Correlation analysis of normalized and PCA-corrected expression data.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-04-19 00:21:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/335528", "https://ndownloader.figshare.com/files/335563", "https://ndownloader.figshare.com/files/335602", "https://ndownloader.figshare.com/files/335646", "https://ndownloader.figshare.com/files/335707", "https://ndownloader.figshare.com/files/335755", "https://ndownloader.figshare.com/files/335801", "https://ndownloader.figshare.com/files/335846", "https://ndownloader.figshare.com/files/335881", "https://ndownloader.figshare.com/files/335933", "https://ndownloader.figshare.com/files/336004", "https://ndownloader.figshare.com/files/336087", "https://ndownloader.figshare.com/files/336149", "https://ndownloader.figshare.com/files/336206", "https://ndownloader.figshare.com/files/336308", "https://ndownloader.figshare.com/files/336363", "https://ndownloader.figshare.com/files/336438", "https://ndownloader.figshare.com/files/336502"], "description"=>"<div><p>The genetic basis of gene expression variation has long been studied with the aim to understand the landscape of regulatory variants, but also more recently to assist in the interpretation and elucidation of disease signals. To date, many studies have looked in specific tissues and population-based samples, but there has been limited assessment of the degree of inter-population variability in regulatory variation. We analyzed genome-wide gene expression in lymphoblastoid cell lines from a total of 726 individuals from 8 global populations from the HapMap3 project and correlated gene expression levels with HapMap3 SNPs located in <em>cis</em> to the genes. We describe the influence of ancestry on gene expression levels within and between these diverse human populations and uncover a non-negligible impact on global patterns of gene expression. We further dissect the specific functional pathways differentiated between populations. We also identify 5,691 expression quantitative trait loci (eQTLs) after controlling for both non-genetic factors and population admixture and observe that half of the <em>cis</em>-eQTLs are replicated in one or more of the populations. We highlight patterns of eQTL-sharing between populations, which are partially determined by population genetic relatedness, and discover significant sharing of eQTL effects between Asians, European-admixed, and African subpopulations. Specifically, we observe that both the effect size and the direction of effect for eQTLs are highly conserved across populations. We observe an increasing proximity of eQTLs toward the transcription start site as sharing of eQTLs among populations increases, highlighting that variants close to TSS have stronger effects and therefore are more likely to be detected across a wider panel of populations. Together these results offer a unique picture and resource of the degree of differentiation among human populations in functional regulatory variation and provide an estimate for the transferability of complex trait variants across populations.</p> </div>", "links"=>[], "tags"=>["patterns", "populations"], "article_id"=>126278, "categories"=>["Genetics"], "users"=>["Barbara E. Stranger", "Stephen B. Montgomery", "Antigone S. Dimas", "Leopold Parts", "Oliver Stegle", "Catherine E. Ingle", "Magda Sekowska", "George Davey Smith", "David Evans", "Maria Gutierrez-Arcelus", "Alkes Price", "Towfique Raj", "James Nisbett", "Alexandra C. Nica", "Claude Beazley", "Richard Durbin", "Panos Deloukas", "Emmanouil T. Dermitzakis"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1002639.s001", "https://dx.doi.org/10.1371/journal.pgen.1002639.s002", "https://dx.doi.org/10.1371/journal.pgen.1002639.s003", "https://dx.doi.org/10.1371/journal.pgen.1002639.s004", "https://dx.doi.org/10.1371/journal.pgen.1002639.s005", "https://dx.doi.org/10.1371/journal.pgen.1002639.s006", "https://dx.doi.org/10.1371/journal.pgen.1002639.s007", "https://dx.doi.org/10.1371/journal.pgen.1002639.s008", "https://dx.doi.org/10.1371/journal.pgen.1002639.s009", "https://dx.doi.org/10.1371/journal.pgen.1002639.s010", "https://dx.doi.org/10.1371/journal.pgen.1002639.s011", "https://dx.doi.org/10.1371/journal.pgen.1002639.s012", "https://dx.doi.org/10.1371/journal.pgen.1002639.s013", "https://dx.doi.org/10.1371/journal.pgen.1002639.s014", "https://dx.doi.org/10.1371/journal.pgen.1002639.s015", "https://dx.doi.org/10.1371/journal.pgen.1002639.s016", "https://dx.doi.org/10.1371/journal.pgen.1002639.s017", "https://dx.doi.org/10.1371/journal.pgen.1002639.s018"], "stats"=>{"downloads"=>14, "page_views"=>24, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Patterns_of_Cis_Regulatory_Variation_in_Diverse_Human_Populations/126278", "title"=>"Patterns of <em>Cis</em> Regulatory Variation in Diverse Human Populations", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-04-19 01:44:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/650271"], "description"=>"<p>Shown are plots of rho for significant associations (permutation threshold 0.01) for each pairwise combination of populations. Within a panel, dots shown in upper left and lower right quadrants indicate significant SNP-probe associations where the allelic direction of the association is in opposite directions in the two populations being compared.</p>", "links"=>[], "tags"=>["rho", "snp-probe"], "article_id"=>320739, "categories"=>["Genetics"], "users"=>["Barbara E. Stranger", "Stephen B. Montgomery", "Antigone S. Dimas", "Leopold Parts", "Oliver Stegle", "Catherine E. Ingle", "Magda Sekowska", "George Davey Smith", "David Evans", "Maria Gutierrez-Arcelus", "Alkes Price", "Towfique Raj", "James Nisbett", "Alexandra C. Nica", "Claude Beazley", "Richard Durbin", "Panos Deloukas", "Emmanouil T. Dermitzakis"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002639.g001", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Spearman_s_rho_for_each_significant_SNP_probe_cis_association_shared_by_at_least_two_populations_/320739", "title"=>"Spearman's rho for each significant SNP-probe <i>cis</i>- association shared by at least two populations.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-04-19 00:12:19"}
  • {"files"=>["https://ndownloader.figshare.com/files/650885"], "description"=>"<p><i>Cis</i>- associations detected with Spearman Rank Correlation analysis of “REDUCED” data.</p>", "links"=>[], "tags"=>["associations", "spearman"], "article_id"=>321358, "categories"=>["Genetics"], "users"=>["Barbara E. Stranger", "Stephen B. Montgomery", "Antigone S. Dimas", "Leopold Parts", "Oliver Stegle", "Catherine E. Ingle", "Magda Sekowska", "George Davey Smith", "David Evans", "Maria Gutierrez-Arcelus", "Alkes Price", "Towfique Raj", "James Nisbett", "Alexandra C. Nica", "Claude Beazley", "Richard Durbin", "Panos Deloukas", "Emmanouil T. Dermitzakis"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002639.t002", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cis_associations_detected_with_Spearman_Rank_Correlation_analysis_of_REDUCED_data_/321358", "title"=>"<i>Cis</i>- associations detected with Spearman Rank Correlation analysis of “REDUCED” data.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-04-19 00:22:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/650703"], "description"=>"<p>−log<sub>10</sub> of the p-value is plotted against distance measured in base pairs from the associated SNP to the TSS. Each dot represents the most significant SNP for a significant gene (permutation threshold 0.01) in a population. Panels separate associations that were significant in one population, two populations, etc. All populations are lumped together.</p>", "links"=>[], "tags"=>["associations", "transcription"], "article_id"=>321175, "categories"=>["Genetics"], "users"=>["Barbara E. Stranger", "Stephen B. Montgomery", "Antigone S. Dimas", "Leopold Parts", "Oliver Stegle", "Catherine E. Ingle", "Magda Sekowska", "George Davey Smith", "David Evans", "Maria Gutierrez-Arcelus", "Alkes Price", "Towfique Raj", "James Nisbett", "Alexandra C. Nica", "Claude Beazley", "Richard Durbin", "Panos Deloukas", "Emmanouil T. Dermitzakis"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002639.g004", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Distribution_of_cis_associations_relative_to_the_transcription_start_site_TSS_and_in_relation_to_population_sharing_/321175", "title"=>"Distribution of <i>cis</i>- associations relative to the transcription start site (TSS) and in relation to population sharing.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-04-19 00:19:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/650578"], "description"=>"<p>−log<sub>10</sub> of the p-value is plotted against distance measured in base pairs from the associated SNP to the TSS. Each dot represents the most significant SNP for a significant gene (permutation threshold 0.01) in a population. Each panel represents a different population.</p>", "links"=>[], "tags"=>["associations", "transcription"], "article_id"=>321048, "categories"=>["Genetics"], "users"=>["Barbara E. Stranger", "Stephen B. Montgomery", "Antigone S. Dimas", "Leopold Parts", "Oliver Stegle", "Catherine E. Ingle", "Magda Sekowska", "George Davey Smith", "David Evans", "Maria Gutierrez-Arcelus", "Alkes Price", "Towfique Raj", "James Nisbett", "Alexandra C. Nica", "Claude Beazley", "Richard Durbin", "Panos Deloukas", "Emmanouil T. Dermitzakis"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002639.g003", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Distribution_of_cis_associations_in_each_population_relative_to_the_transcription_start_site_TSS_/321048", "title"=>"Distribution of <i>cis</i>- associations in each population relative to the transcription start site (TSS).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-04-19 00:17:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/650376"], "description"=>"<p>Shown are plots of the absolute value of expression level fold-change between median expression levels of homozygote classes for significant associations (permutation threshold 0.01) for each pairwise combination of populations. Within a panel, deviating from the 1 to 1 line (lower left to upper right) indicates differences in expression level fold-change (effect size) on log<sub>2</sub> scale in the two populations being compared.</p>", "links"=>[], "tags"=>["fold-change", "snp-probe", "associations", "pairs"], "article_id"=>320850, "categories"=>["Genetics"], "users"=>["Barbara E. Stranger", "Stephen B. Montgomery", "Antigone S. Dimas", "Leopold Parts", "Oliver Stegle", "Catherine E. Ingle", "Magda Sekowska", "George Davey Smith", "David Evans", "Maria Gutierrez-Arcelus", "Alkes Price", "Towfique Raj", "James Nisbett", "Alexandra C. Nica", "Claude Beazley", "Richard Durbin", "Panos Deloukas", "Emmanouil T. Dermitzakis"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002639.g002", "stats"=>{"downloads"=>5, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_level_fold_change_for_significant_SNP_probe_cis_associations_shared_by_pairs_of_populations_/320850", "title"=>"Expression level fold-change for significant SNP-probe <i>cis</i>- associations shared by pairs of populations.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-04-19 00:14:10"}

PMC Usage Stats | Further Information

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Relative Metric

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