Genome-Wide Detection of Allele Specific Copy Number Variation Associated with Insulin Resistance in African Americans from the HyperGEN Study
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{"title"=>"Genome-wide detection of allele specific copy number variation associated with insulin resistance in african americans from the hyperGEN study", "type"=>"journal", "authors"=>[{"first_name"=>"Marguerite R.", "last_name"=>"Irvin", "scopus_author_id"=>"28567762900"}, {"first_name"=>"Nathan E.", "last_name"=>"Wineinger", "scopus_author_id"=>"23993144000"}, {"first_name"=>"Treva K.", "last_name"=>"Rice", "scopus_author_id"=>"7201893716"}, {"first_name"=>"Nicholas M.", "last_name"=>"Pajewski", "scopus_author_id"=>"12769441600"}, {"first_name"=>"Edmond K.", "last_name"=>"Kabagambe", "scopus_author_id"=>"6602704484"}, {"first_name"=>"Charles C.", "last_name"=>"Gu", "scopus_author_id"=>"24775504800"}, {"first_name"=>"Jim", "last_name"=>"Pankow", "scopus_author_id"=>"7101854959"}, {"first_name"=>"Kari E.", "last_name"=>"North", "scopus_author_id"=>"7006800602"}, {"first_name"=>"Jemma B.", "last_name"=>"Wilk", "scopus_author_id"=>"7006234698"}, {"first_name"=>"Barry I.", "last_name"=>"Freedman", "scopus_author_id"=>"7102825752"}, {"first_name"=>"Nora", "last_name"=>"Franceschini", "scopus_author_id"=>"7006270916"}, {"first_name"=>"Uli", "last_name"=>"Broeckel", "scopus_author_id"=>"6602617506"}, {"first_name"=>"Hemant K.", "last_name"=>"Tiwari", "scopus_author_id"=>"7003376624"}, {"first_name"=>"Donna K.", "last_name"=>"Arnett", "scopus_author_id"=>"7101719250"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"80052067433", "doi"=>"10.1371/journal.pone.0024052", "pui"=>"362414984", "issn"=>"19326203", "pmid"=>"21901158", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "scopus"=>"2-s2.0-80052067433"}, "id"=>"1fc2d989-0b33-3c48-8297-4492314c3903", "abstract"=>"African Americans have been understudied in genome wide association studies of diabetes and related traits. In the current study, we examined the joint association of single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) with fasting insulin and an index of insulin resistance (HOMA-IR) in the HyperGEN study, a family based study with proband ascertainment for hypertension. This analysis is restricted to 1,040 African Americans without diabetes. We generated allele specific CNV genotypes at 872,243 autosomal loci using Birdsuite, a freely available multi-stage program. Joint tests of association for SNPs and CNVs were performed using linear mixed models adjusting for covariates and familial relationships. Our results highlight SNPs associated with fasting insulin and HOMA-IR (rs6576507 and rs8026527, 3.7*10(-7)≤P≤1.1*10(-5)) near ATPase, class V, type 10A (ATP10A), and the L Type voltage dependent calcium channel (CACNA1D, rs1401492, P≤5.2*10(-6)). ATP10A belongs to a family of aminophospholipid-transporting ATPases and has been associated with type 2 diabetes in mice. CACNA1D has been linked to pancreatic beta cell generation in mice. The two most significant copy variable markers (rs10277702 and rs361367; P<2.0*10(-4)) were in the beta variable region of the T-cell receptor gene (TCRVB). Human and mouse TCR has been shown to mimic insulin and its receptor and could contribute to insulin resistance. Our findings differ from genome wide association studies of fasting insulin and other diabetes related traits in European populations, highlighting the continued need to investigate unique genetic influences for understudied populations such as African Americans.", "link"=>"http://www.mendeley.com/research/genomewide-detection-allele-specific-copy-number-variation-associated-insulin-resistance-african-ame", "reader_count"=>33, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>4, "Researcher"=>6, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>12, "Student > Postgraduate"=>1, "Student > Master"=>5, "Other"=>2, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>4, "Researcher"=>6, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>12, "Student > Postgraduate"=>1, "Student > Master"=>5, "Other"=>2, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>2, "Mathematics"=>1, "Agricultural and Biological Sciences"=>19, "Medicine and Dentistry"=>9, "Sports and Recreations"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>9}, "Sports and Recreations"=>{"Sports and Recreations"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>19}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"Canada"=>1, "United States"=>4, "Italy"=>1, "France"=>1}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/741767"], "description"=>"†<p>For more detailed information about these markers see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0024052#pone.0024052.s003\" target=\"_blank\">Table S1</a>.</p>‡<p>A<sub>1</sub> is the modeled and minor allele.</p><p>*nearest gene within a 200 kb window on either side of the marker (if gene is italicized the marker lies in the gene).</p>", "links"=>[], "tags"=>["loci", "fasting", "insulin", "homa-ir", "african", "americans"], "article_id"=>412123, "categories"=>["Chemistry", "Biological Sciences", "Physiology", "Genetics", "Biotechnology"], "users"=>["Marguerite R. Irvin", "Nathan E. Wineinger", "Treva K. Rice", "Nicholas M. Pajewski", "Edmond K. Kabagambe", "Charles C. Gu", "Jim Pankow", "Kari E. North", "Jemma B. Wilk", "Barry I. Freedman", "Nora Franceschini", "Uli Broeckel", "Hemant K. Tiwari", "Donna K. Arnett"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0024052.t001", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Top_loci_associated_with_fasting_insulin_ln_181_IU_mL_and_HOMA_IR_in_African_Americans_without_diabetes_from_HyperGEN_/412123", "title"=>"Top loci associated with fasting insulin [ln(µIU/mL)] and HOMA-IR in African Americans without diabetes from HyperGEN.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-08-25 00:35:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/374634", "https://ndownloader.figshare.com/files/374661", "https://ndownloader.figshare.com/files/374687", "https://ndownloader.figshare.com/files/374712"], "description"=>"<div><p>African Americans have been understudied in genome wide association studies of diabetes and related traits. In the current study, we examined the joint association of single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) with fasting insulin and an index of insulin resistance (HOMA-IR) in the HyperGEN study, a family based study with proband ascertainment for hypertension. This analysis is restricted to 1,040 African Americans without diabetes. We generated allele specific CNV genotypes at 872,243 autosomal loci using <em>Birdsuite</em>, a freely available multi-stage program. Joint tests of association for SNPs and CNVs were performed using linear mixed models adjusting for covariates and familial relationships. Our results highlight SNPs associated with fasting insulin and HOMA-IR (rs6576507 and rs8026527, 3.7*10<sup>−7</sup>≤<em>P</em>≤1.1*10<sup>−5</sup>) near ATPase, class V, type 10A (<em>ATP10A</em>), and the L Type voltage dependent calcium channel (<em>CACNA1D,</em> rs1401492, <em>P</em>≤5.2*10<sup>−6</sup>). <em>ATP10A</em> belongs to a family of aminophospholipid-transporting ATPases and has been associated with type 2 diabetes in mice. <em>CACNA1D</em> has been linked to pancreatic beta cell generation in mice. The two most significant copy variable markers (rs10277702 and rs361367; <em>P</em><2.0*10<sup>−4</sup>) were in the beta variable region of the T-cell receptor gene (<em>TCRVB</em>). Human and mouse TCR has been shown to mimic insulin and its receptor and could contribute to insulin resistance. Our findings differ from genome wide association studies of fasting insulin and other diabetes related traits in European populations, highlighting the continued need to investigate unique genetic influences for understudied populations such as African Americans.</p> </div>", "links"=>[], "tags"=>["genome-wide", "detection", "allele", "insulin", "african", "americans", "hypergen"], "article_id"=>133978, "categories"=>["Chemistry", "Biological Sciences", "Physiology", "Genetics", "Biotechnology"], "users"=>["Marguerite R. Irvin", "Nathan E. Wineinger", "Treva K. Rice", "Nicholas M. Pajewski", "Edmond K. Kabagambe", "Charles C. Gu", "Jim Pankow", "Kari E. North", "Jemma B. Wilk", "Barry I. Freedman", "Nora Franceschini", "Uli Broeckel", "Hemant K. Tiwari", "Donna K. Arnett"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0024052.s001", "https://dx.doi.org/10.1371/journal.pone.0024052.s002", "https://dx.doi.org/10.1371/journal.pone.0024052.s003", "https://dx.doi.org/10.1371/journal.pone.0024052.s004"], "stats"=>{"downloads"=>4, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Genome_Wide_Detection_of_Allele_Specific_Copy_Number_Variation_Associated_with_Insulin_Resistance_in_African_Americans_from_the_HyperGEN_Study/133978", "title"=>"Genome-Wide Detection of Allele Specific Copy Number Variation Associated with Insulin Resistance in African Americans from the HyperGEN Study", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2011-08-25 01:06:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/741823"], "description"=>"†<p>For more detailed information about these markers see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0024052#pone.0024052.s003\" target=\"_blank\">Table S1</a>.</p>‡<p>A<sub>1</sub> is the modeled/minor allele for which frequency (freq) is reported.</p><p>*nearest gene within a 200 kb window on either side of the marker (if gene is italicized the marker lies in the gene).</p>", "links"=>[], "tags"=>["loci", "fasting", "insulin", "homa-ir", "african", "americans"], "article_id"=>412179, "categories"=>["Chemistry", "Biological Sciences", "Physiology", "Genetics", "Biotechnology"], "users"=>["Marguerite R. Irvin", "Nathan E. Wineinger", "Treva K. Rice", "Nicholas M. Pajewski", "Edmond K. Kabagambe", "Charles C. Gu", "Jim Pankow", "Kari E. North", "Jemma B. Wilk", "Barry I. Freedman", "Nora Franceschini", "Uli Broeckel", "Hemant K. Tiwari", "Donna K. Arnett"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0024052.t002", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Top_copy_variable_loci_associated_with_fasting_insulin_ln_181_IU_mL_and_HOMA_IR_in_African_Americans_without_diabetes_from_HyperGEN_/412179", "title"=>"Top copy variable loci associated with fasting insulin [ln(µIU/mL)] and HOMA-IR in African Americans without diabetes from HyperGEN.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-08-25 00:36:19"}

PMC Usage Stats | Further Information

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Relative Metric

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