Cis-Regulatory Variants Affect CHRNA5 mRNA Expression in Populations of African and European Ancestry
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{"title"=>"Cis-regulatory variants affect CHRNA5 mRNA expression in populations of African and European ancestry", "type"=>"journal", "authors"=>[{"first_name"=>"Jen Chyong", "last_name"=>"Wang", "scopus_author_id"=>"10143890400"}, {"first_name"=>"Noah", "last_name"=>"Spiegel", "scopus_author_id"=>"25423158500"}, {"first_name"=>"Sarah", "last_name"=>"Bertelsen", "scopus_author_id"=>"7004382710"}, {"first_name"=>"Nhung", "last_name"=>"Le", "scopus_author_id"=>"55413039700"}, {"first_name"=>"Nicholas", "last_name"=>"McKenna", "scopus_author_id"=>"55576787100"}, {"first_name"=>"John P.", "last_name"=>"Budde", "scopus_author_id"=>"57201211354"}, {"first_name"=>"Oscar", "last_name"=>"Harari", "scopus_author_id"=>"57195300833"}, {"first_name"=>"Manav", "last_name"=>"Kapoor", "scopus_author_id"=>"55286199400"}, {"first_name"=>"Andrew", "last_name"=>"Brooks", "scopus_author_id"=>"7202570520"}, {"first_name"=>"Dana", "last_name"=>"Hancock", "scopus_author_id"=>"14828970000"}, {"first_name"=>"Jay", "last_name"=>"Tischfield", "scopus_author_id"=>"7004449404"}, {"first_name"=>"Tatiana", "last_name"=>"Foroud", "scopus_author_id"=>"7006590374"}, {"first_name"=>"Laura J.", "last_name"=>"Bierut", "scopus_author_id"=>"6701374894"}, {"first_name"=>"Joe Henry", "last_name"=>"Steinbach", "scopus_author_id"=>"7103124614"}, {"first_name"=>"Howard J.", "last_name"=>"Edenberg", "scopus_author_id"=>"7006853081"}, {"first_name"=>"Bryan J.", "last_name"=>"Traynor", "scopus_author_id"=>"6701852117"}, {"first_name"=>"Alison M.", "last_name"=>"Goate", "scopus_author_id"=>"7006308333"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84896731443", "doi"=>"10.1371/journal.pone.0080204", "sgr"=>"84896731443", "pmid"=>"24303001", "issn"=>"19326203", "pui"=>"372438559"}, "id"=>"d075b416-6b84-3885-8f3f-c3d7f21d8266", "abstract"=>"Variants within the gene cluster encoding α3, α5, and β4 nicotinic receptor subunits are major risk factors for substance dependence. The strongest impact on risk is associated with variation in the CHRNA5 gene, where at least two mechanisms are at work: amino acid variation and altered mRNA expression levels. The risk allele of the non-synonymous variant (rs16969968; D398N) primarily occurs on the haplotype containing the low mRNA expression allele. In populations of European ancestry, there are approximately 50 highly correlated variants in the CHRNA5-CHRNA3-CHRNB4 gene cluster and the adjacent PSMA4 gene region that are associated with CHRNA5 mRNA levels. It is not clear which of these variants contribute to the changes in CHRNA5 transcript level. Because populations of African ancestry have reduced linkage disequilibrium among variants spanning this gene cluster, eQTL mapping in subjects of African ancestry could potentially aid in defining the functional variants that affect CHRNA5 mRNA levels. We performed quantitative allele specific gene expression using frontal cortices derived from 49 subjects of African ancestry and 111 subjects of European ancestry. This method measures allele-specific transcript levels in the same individual, which eliminates other biological variation that occurs when comparing expression levels between different samples. This analysis confirmed that substance dependence associated variants have a direct cis-regulatory effect on CHRNA5 transcript levels in human frontal cortices of African and European ancestry and identified 10 highly correlated variants, located in a 9 kb region, that are potential functional variants modifying CHRNA5 mRNA expression levels.", "link"=>"http://www.mendeley.com/research/cisregulatory-variants-affect-chrna5-mrna-expression-populations-african-european-ancestry", "reader_count"=>17, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>2, "Student > Master"=>1, "Other"=>2, "Student > Bachelor"=>1, "Professor"=>5}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>2, "Student > Master"=>1, "Other"=>2, "Student > Bachelor"=>1, "Professor"=>5}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>6, "Medicine and Dentistry"=>3, "Neuroscience"=>4}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Neuroscience"=>{"Neuroscience"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>6}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>3}}, "reader_count_by_country"=>{"Canada"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1295453"], "description"=>"<p>SNPs in red indicate potential functional eQTLs. Note: figure is not drawn to scale.</p>", "links"=>[], "tags"=>["schematic"], "article_id"=>862317, "categories"=>["Biological Sciences"], "users"=>["Jen-Chyong Wang", "Noah Spiegel", "Sarah Bertelsen", "Nhung Le", "Nicholas McKenna", "John P. Budde", "Oscar Harari", "Manav Kapoor", "Andrew Brooks", "Dana Hancock", "Jay Tischfield", "Tatiana Foroud", "Laura J. Bierut", "Joe Henry Steinbach", "Howard J. Edenberg", "Bryan J. Traynor", "Alison M. Goate"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0080204.g005", "stats"=>{"downloads"=>0, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_schematic_of_CHRNA5_and_PSMA4_gene_structures_/862317", "title"=>"A schematic of <i>CHRNA5</i> and <i>PSMA4</i> gene structures.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-26 03:00:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1295449"], "description"=>"<p>3a. Davies-Bouldin (DB) validity index analysis. Columns represent the ASE. Dotted line represents the DB validity index. The red dot indicates the optimal cutoff predicted by the DB index that coincides with ASE. 3b. Concordance of allelic expression variation with heterozygosity. Samples #1 to #6 which show relative allelic expression balance (*ASE<2) are homozygous for the 13 highlighted SNPs. Samples #7 to #45 which showed relative allelic expression imbalance are heterozygous for all 13 SNPs. *See <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0080204#s2\" target=\"_blank\">material and method</a> for details; ASE: allele specific expression. † Indicates samples are also heterozygous for rs16969968.</p>", "links"=>[], "tags"=>["rs615470", "45", "frontal", "cortices", "european"], "article_id"=>862313, "categories"=>["Biological Sciences"], "users"=>["Jen-Chyong Wang", "Noah Spiegel", "Sarah Bertelsen", "Nhung Le", "Nicholas McKenna", "John P. Budde", "Oscar Harari", "Manav Kapoor", "Andrew Brooks", "Dana Hancock", "Jay Tischfield", "Tatiana Foroud", "Laura J. Bierut", "Joe Henry Steinbach", "Howard J. Edenberg", "Bryan J. Traynor", "Alison M. Goate"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0080204.g003", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Allele_specific_expression_ASE_analysis_with_rs615470_in_45_frontal_cortices_of_European_ancestry_/862313", "title"=>"Allele specific expression (ASE) analysis with rs615470 in 45 frontal cortices of European ancestry.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-26 03:00:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1295446"], "description"=>"<p>2a. Davies-Bouldin (DB) validity index analysis. Columns represent the ASE. Dotted line represents the DB validity index. The red dot indicates the optimal cutoff predicted by the DB index that coincides with ASE. 2b. Concordance of allelic expression variation with heterozygosity. Samples #1 to #14 which show relative allelic expression balance (*ASE<2) are homozygous for the 13 highlighted SNPs. Samples #15 to #44 which show relative allelic expression imbalance are heterozygous for all 13 SNPs. *See <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0080204#s2\" target=\"_blank\">material and method</a> for details; ASE: allele specific expression. † Indicates samples are also heterozygous for rs615470.</p>", "links"=>[], "tags"=>["rs16969968", "44", "frontal", "cortices", "european"], "article_id"=>862310, "categories"=>["Biological Sciences"], "users"=>["Jen-Chyong Wang", "Noah Spiegel", "Sarah Bertelsen", "Nhung Le", "Nicholas McKenna", "John P. Budde", "Oscar Harari", "Manav Kapoor", "Andrew Brooks", "Dana Hancock", "Jay Tischfield", "Tatiana Foroud", "Laura J. Bierut", "Joe Henry Steinbach", "Howard J. Edenberg", "Bryan J. Traynor", "Alison M. Goate"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0080204.g002", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Allele_specific_expression_ASE_analysis_with_rs16969968_in_44_frontal_cortices_of_European_ancestry_/862310", "title"=>"Allele specific expression (ASE) analysis with rs16969968 in 44 frontal cortices of European ancestry.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-26 03:00:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1295436"], "description"=>"<p>Minor allele of rs880395 (A allele), rs3841324 (S allele) and rs588765 (T allele) are associated with increased total mRNA expression of <i>CHRNA5</i> in human frontal cortex of African Americans.</p>", "links"=>[], "tags"=>["allele", "rs880395", "rs3841324", "rs588765", "mrna", "frontal", "cortex", "african"], "article_id"=>862306, "categories"=>["Biological Sciences"], "users"=>["Jen-Chyong Wang", "Noah Spiegel", "Sarah Bertelsen", "Nhung Le", "Nicholas McKenna", "John P. Budde", "Oscar Harari", "Manav Kapoor", "Andrew Brooks", "Dana Hancock", "Jay Tischfield", "Tatiana Foroud", "Laura J. Bierut", "Joe Henry Steinbach", "Howard J. Edenberg", "Bryan J. Traynor", "Alison M. Goate"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0080204.g001", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Minor_allele_of_rs880395_A_allele_rs3841324_S_allele_and_rs588765_T_allele_are_associated_with_increased_total_mRNA_expression_of_CHRNA5_in_human_frontal_cortex_of_African_Americans_/862306", "title"=>"Minor allele of rs880395 (A allele), rs3841324 (S allele) and rs588765 (T allele) are associated with increased total mRNA expression of <i>CHRNA5</i> in human frontal cortex of African Americans.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-26 03:00:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1295455"], "description"=>"<p>*Bolded beta values indicate variants with significant association between minor alleles and increased mRNA expression.</p>", "links"=>[], "tags"=>["mrna", "variants", "flanking"], "article_id"=>862319, "categories"=>["Biological Sciences"], "users"=>["Jen-Chyong Wang", "Noah Spiegel", "Sarah Bertelsen", "Nhung Le", "Nicholas McKenna", "John P. Budde", "Oscar Harari", "Manav Kapoor", "Andrew Brooks", "Dana Hancock", "Jay Tischfield", "Tatiana Foroud", "Laura J. Bierut", "Joe Henry Steinbach", "Howard J. Edenberg", "Bryan J. Traynor", "Alison M. Goate"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0080204.t001", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Association_of_CHRNA5_total_mRNA_expression_with_variants_within_and_flanking_the_CHRNA5_gene_/862319", "title"=>"Association of <i>CHRNA5</i> total mRNA expression with variants within and flanking the <i>CHRNA5</i> gene.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-11-26 03:00:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1295451"], "description"=>"<p>4a. Davies-Bouldin (DB) validity index analysis. Columns represent the ASE. Dotted line represents the DB validity index. The red dot indicates the optimal d cutoff predicted by the DB index that coincides with ASE. 4b. Concordance of allelic expression variation with heterozygosity. Samples #1 to #5 which show relative allelic expression balance (*ASE<2) are homozygous for all 10 SNPs highlighted. Samples #6 to #15 which show relative allelic expression imbalance are heterozygous for all 10 SNPs. *See <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0080204#s2\" target=\"_blank\">material and method</a> for details; ASE: relative allele specific expression.</p>", "links"=>[], "tags"=>["rs615470", "15", "frontal", "cortices", "african"], "article_id"=>862315, "categories"=>["Biological Sciences"], "users"=>["Jen-Chyong Wang", "Noah Spiegel", "Sarah Bertelsen", "Nhung Le", "Nicholas McKenna", "John P. Budde", "Oscar Harari", "Manav Kapoor", "Andrew Brooks", "Dana Hancock", "Jay Tischfield", "Tatiana Foroud", "Laura J. Bierut", "Joe Henry Steinbach", "Howard J. Edenberg", "Bryan J. Traynor", "Alison M. Goate"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0080204.g004", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Allele_specific_expression_ASE_analysis_with_rs615470_in_15_frontal_cortices_of_African_ancestry_/862315", "title"=>"Allele specific expression (ASE) analysis with rs615470 in 15 frontal cortices of African ancestry.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-26 03:00:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1295462", "https://ndownloader.figshare.com/files/1295463", "https://ndownloader.figshare.com/files/1295464", "https://ndownloader.figshare.com/files/1295466", "https://ndownloader.figshare.com/files/1295467"], "description"=>"<div><p>Variants within the gene cluster encoding α3, α5, and β4 nicotinic receptor subunits are major risk factors for substance dependence. The strongest impact on risk is associated with variation in the <i>CHRNA5</i> gene, where at least two mechanisms are at work: amino acid variation and altered mRNA expression levels. The risk allele of the non-synonymous variant (rs16969968; D398N) primarily occurs on the haplotype containing the low mRNA expression allele. In populations of European ancestry, there are approximately 50 highly correlated variants in the <i>CHRNA5-CHRNA3-CHRNB4</i> gene cluster and the adjacent <i>PSMA4</i> gene region that are associated with <i>CHRNA5</i> mRNA levels. It is not clear which of these variants contribute to the changes in <i>CHRNA5</i> transcript level. Because populations of African ancestry have reduced linkage disequilibrium among variants spanning this gene cluster, eQTL mapping in subjects of African ancestry could potentially aid in defining the functional variants that affect <i>CHRNA5</i> mRNA levels. We performed quantitative allele specific gene expression using frontal cortices derived from 49 subjects of African ancestry and 111 subjects of European ancestry. This method measures allele-specific transcript levels in the same individual, which eliminates other biological variation that occurs when comparing expression levels between different samples. This analysis confirmed that substance dependence associated variants have a direct <i>cis</i>-regulatory effect on <i>CHRNA5</i> transcript levels in human frontal cortices of African and European ancestry and identified 10 highly correlated variants, located in a 9 kb region, that are potential functional variants modifying <i>CHRNA5</i> mRNA expression levels.</p></div>", "links"=>[], "tags"=>["variants", "mrna", "populations", "african", "european", "ancestry"], "article_id"=>862326, "categories"=>["Biological Sciences"], "users"=>["Jen-Chyong Wang", "Noah Spiegel", "Sarah Bertelsen", "Nhung Le", "Nicholas McKenna", "John P. Budde", "Oscar Harari", "Manav Kapoor", "Andrew Brooks", "Dana Hancock", "Jay Tischfield", "Tatiana Foroud", "Laura J. Bierut", "Joe Henry Steinbach", "Howard J. Edenberg", "Bryan J. Traynor", "Alison M. Goate"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0080204.s001", "https://dx.doi.org/10.1371/journal.pone.0080204.s002", "https://dx.doi.org/10.1371/journal.pone.0080204.s003", "https://dx.doi.org/10.1371/journal.pone.0080204.s004", "https://dx.doi.org/10.1371/journal.pone.0080204.s005"], "stats"=>{"downloads"=>12, "page_views"=>21, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cis_Regulatory_Variants_Affect_CHRNA5_mRNA_Expression_in_Populations_of_African_and_European_Ancestry/862326", "title"=>"<i>Cis</i>-Regulatory Variants Affect <i>CHRNA5</i> mRNA Expression in Populations of African and European Ancestry", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-11-26 03:00:57"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"4", "full-text"=>"5", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
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  • {"unique-ip"=>"5", "full-text"=>"7", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"5", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
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Relative Metric

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