A Genome-Wide Association Study of Red Blood Cell Traits Using the Electronic Medical Record
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{"title"=>"A genome-wide association study of red blood cell traits using the Electronic Medical Record", "type"=>"journal", "authors"=>[{"first_name"=>"Iftikhar J.", "last_name"=>"Kullo", "scopus_author_id"=>"6701817256"}, {"first_name"=>"Keyue", "last_name"=>"Ding", "scopus_author_id"=>"55432278900"}, {"first_name"=>"Hayan", "last_name"=>"Jouni", "scopus_author_id"=>"36623708800"}, {"first_name"=>"Carin Y.", "last_name"=>"Smith", "scopus_author_id"=>"37038372100"}, {"first_name"=>"Christopher G.", "last_name"=>"Chute", "scopus_author_id"=>"7006581202"}], "year"=>2010, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"359839272", "issn"=>"19326203", "isbn"=>"1932-6203", "doi"=>"10.1371/journal.pone.0013011", "scopus"=>"2-s2.0-77958522275", "pmid"=>"20927387", "sgr"=>"77958522275"}, "id"=>"f45b486b-b443-388f-87fa-6e43a926c1bf", "abstract"=>"BACKGROUND: The Electronic Medical Record (EMR) is a potential source for high throughput phenotyping to conduct genome-wide association studies (GWAS), including those of medically relevant quantitative traits. We describe use of the Mayo Clinic EMR to conduct a GWAS of red blood cell (RBC) traits in a cohort of patients with peripheral arterial disease (PAD) and controls without PAD. METHODOLOGY AND PRINCIPAL FINDINGS: Results for hemoglobin level, hematocrit, RBC count, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration were extracted from the EMR from January 1994 to September 2009. Out of 35,159 RBC trait values in 3,411 patients, we excluded 12,864 values in 1,165 patients that had been measured during hospitalization or in the setting of hematological disease, malignancy, or use of drugs that affect RBC traits, leaving a final genotyped sample of 3,012, 80% of whom had ≥2 measurements. The median of each RBC trait was used in the genetic analyses, which were conducted using an additive model that adjusted for age, sex, and PAD status. We identified four genomic loci that were associated (P<5 × 10(-8)) with one or more of the RBC traits (HBLS1/MYB on 6q23.3, TMPRSS6 on 22q12.3, HFE on 6p22.1, and SLC17A1 on 6p22.2). Three of these loci (HBLS1/MYB, TMPRSS6, and HFE) had been identified in recent GWAS and the allele frequencies, effect sizes, and the directions of effects of the replicated SNPs were similar to the prior studies. CONCLUSIONS: Our results demonstrate feasibility of using the EMR to conduct high throughput genomic studies of medically relevant quantitative traits.", "link"=>"http://www.mendeley.com/research/genomewide-association-study-red-blood-cell-traits-using-electronic-medical-record-2", "reader_count"=>40, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>7, "Student > Doctoral Student"=>1, "Researcher"=>8, "Student > Ph. D. Student"=>13, "Student > Postgraduate"=>1, "Student > Master"=>3, "Other"=>2, "Student > Bachelor"=>2, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>7, "Student > Doctoral Student"=>1, "Researcher"=>8, "Student > Ph. D. Student"=>13, "Student > Postgraduate"=>1, "Student > Master"=>3, "Other"=>2, "Student > Bachelor"=>2, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Engineering"=>2, "Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>18, "Medicine and Dentistry"=>11, "Social Sciences"=>3, "Computer Science"=>2}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>2}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>11}, "Social Sciences"=>{"Social Sciences"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>18}, "Computer Science"=>{"Computer Science"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"Canada"=>1, "United States"=>2}, "group_count"=>6}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/828261"], "description"=>"<p>*The direction of effect of rs4895441 in Ganesh et al. <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0013011#pone.0013011-Ganesh1\" target=\"_blank\">[7]</a> is based on the major allele (A) instead of the minor allele (G).</p><p>#: Frequency of effect allele (the present study) in the HapMap CEU population.</p>", "links"=>[], "tags"=>["sizes", "snps", "GWAS", "rbc"], "article_id"=>498626, "categories"=>["Genetics", "Medicine", "Hematology"], "users"=>["Iftikhar J. Kullo", "Keyue Ding", "Hayan Jouni", "Carin Y. Smith", "Christopher G. Chute"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0013011.t003", "stats"=>{"downloads"=>2, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparison_of_the_effect_sizes_of_significant_SNPs_with_those_identified_in_previous_GWAS_for_RBC_traits_/498626", "title"=>"Comparison of the effect sizes of significant SNPs with those identified in previous GWAS for RBC traits.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2010-09-28 02:23:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/828194"], "description"=>"<p>*hemojuvelin is essential for production of the iron regulatory hormone hepcidin <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0013011#pone.0013011-Babitt1\" target=\"_blank\">[27]</a>.</p>", "links"=>[], "tags"=>["cardiovascular disorders", "hematology", "genetics and genomics/complex traits"], "article_id"=>498563, "categories"=>["Genetics", "Medicine", "Hematology"], "users"=>["Iftikhar J. Kullo", "Keyue Ding", "Hayan Jouni", "Carin Y. Smith", "Christopher G. Chute"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0013011.t004", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Molecular_function_of_associated_loci_/498563", "title"=>"Molecular function of associated loci.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2010-09-28 02:22:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/827970"], "description"=>"<p>The vertical axis indicates (–log<sub>10</sub> transformed) observed <i>P</i> values; and the horizontal line indicates the genome-wide significant level of <i>P</i> = 5×10<sup>−8</sup>.</p>", "links"=>[], "tags"=>["plots", "GWAS", "analyses", "rbc"], "article_id"=>498340, "categories"=>["Genetics", "Medicine", "Hematology"], "users"=>["Iftikhar J. Kullo", "Keyue Ding", "Hayan Jouni", "Carin Y. Smith", "Christopher G. Chute"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0013011.g003", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Manhattan_plots_for_GWAS_analyses_of_RBC_traits_/498340", "title"=>"Manhattan plots for GWAS analyses of RBC traits.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-09-28 02:19:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/412137", "https://ndownloader.figshare.com/files/412146", "https://ndownloader.figshare.com/files/412152", "https://ndownloader.figshare.com/files/412156", "https://ndownloader.figshare.com/files/412164", "https://ndownloader.figshare.com/files/412167", "https://ndownloader.figshare.com/files/412172", "https://ndownloader.figshare.com/files/412176", "https://ndownloader.figshare.com/files/412178"], "description"=>"<div><h3>Background</h3><p>The Electronic Medical Record (EMR) is a potential source for high throughput phenotyping to conduct genome-wide association studies (GWAS), including those of medically relevant quantitative traits. We describe use of the Mayo Clinic EMR to conduct a GWAS of red blood cell (RBC) traits in a cohort of patients with peripheral arterial disease (PAD) and controls without PAD.</p><h3>Methodology and Principal Findings</h3><p>Results for hemoglobin level, hematocrit, RBC count, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration were extracted from the EMR from January 1994 to September 2009. Out of 35,159 RBC trait values in 3,411 patients, we excluded 12,864 values in 1,165 patients that had been measured during hospitalization or in the setting of hematological disease, malignancy, or use of drugs that affect RBC traits, leaving a final genotyped sample of 3,012, 80% of whom had ≥2 measurements. The median of each RBC trait was used in the genetic analyses, which were conducted using an additive model that adjusted for age, sex, and PAD status. We identified four genomic loci that were associated (<em>P</em><5×10<sup>−8</sup>) with one or more of the RBC traits (<em>HBLS1/MYB</em> on 6q23.3, <em>TMPRSS6</em> on 22q12.3, <em>HFE</em> on 6p22.1, and <em>SLC17A1</em> on 6p22.2). Three of these loci (<em>HBLS1/MYB</em>, <em>TMPRSS6</em>, and <em>HFE</em>) had been identified in recent GWAS and the allele frequencies, effect sizes, and the directions of effects of the replicated SNPs were similar to the prior studies.</p><h3>Conclusions</h3><p>Our results demonstrate feasibility of using the EMR to conduct high throughput genomic studies of medically relevant quantitative traits.</p></div>", "links"=>[], "tags"=>["genome-wide", "traits"], "article_id"=>141414, "categories"=>["Genetics", "Medicine", "Hematology"], "users"=>["Iftikhar J. Kullo", "Keyue Ding", "Hayan Jouni", "Carin Y. Smith", "Christopher G. Chute"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0013011.s001", "https://dx.doi.org/10.1371/journal.pone.0013011.s002", "https://dx.doi.org/10.1371/journal.pone.0013011.s003", "https://dx.doi.org/10.1371/journal.pone.0013011.s004", "https://dx.doi.org/10.1371/journal.pone.0013011.s005", "https://dx.doi.org/10.1371/journal.pone.0013011.s006", "https://dx.doi.org/10.1371/journal.pone.0013011.s007", "https://dx.doi.org/10.1371/journal.pone.0013011.s008", "https://dx.doi.org/10.1371/journal.pone.0013011.s009"], "stats"=>{"downloads"=>39, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/A_Genome_Wide_Association_Study_of_Red_Blood_Cell_Traits_Using_the_Electronic_Medical_Record/141414", "title"=>"A Genome-Wide Association Study of Red Blood Cell Traits Using the Electronic Medical Record", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2010-09-28 00:23:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/828230"], "description"=>"<p>The asterisk indicates the three replicated SNPs.</p>", "links"=>[], "tags"=>["variants", "rbc"], "article_id"=>498599, "categories"=>["Genetics", "Medicine", "Hematology"], "users"=>["Iftikhar J. Kullo", "Keyue Ding", "Hayan Jouni", "Carin Y. Smith", "Christopher G. Chute"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0013011.t002", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Genetic_variants_associated_with_RBC_traits_/498599", "title"=>"Genetic variants associated with RBC traits.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2010-09-28 02:23:19"}
  • {"files"=>["https://ndownloader.figshare.com/files/828298"], "description"=>"<p>Continuous variables are presented as mean ± SD; in addition, for the six RBC traits, the [25% quartile, median, 75% quartile] is also listed; categorical variables are presented as percentages (%).</p>", "links"=>[], "tags"=>["cardiovascular disorders", "hematology", "genetics and genomics/complex traits"], "article_id"=>498666, "categories"=>["Genetics", "Medicine", "Hematology"], "users"=>["Iftikhar J. Kullo", "Keyue Ding", "Hayan Jouni", "Carin Y. Smith", "Christopher G. Chute"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0013011.t001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Sample_characteristics_/498666", "title"=>"Sample characteristics.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2010-09-28 02:24:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/828120"], "description"=>"<p>A. Regional plots of loci associated with RBC traits on chromosome 6q23.3: 135,450 kb – 135,520 kb. The top panel indicates the negative logarithm of observed <i>P</i> value, and the bottom panel indicates the patterns of LD based on HapMap (<a href=\"http://www.hapmap.org\" target=\"_blank\">www.hapmap.org</a>) CEU population. <i>HBS1L</i> (NM_006620) is located from bp 135,417,715 to 135,323,216; and <i>MYB</i> (NM_005375) is located from bp 135,544,146 to 135,582,002. B. Regional plots of loci associated with RBC traits on chromosome 22q12.3: 35,791 kb – 35,840 kb. <i>TMPRSS6</i> (NM_153609) is located from bp 35,791,425 to 35,829,639. Gene structure of <i>TMPRSS6</i> is shown. C. Regional plots of loci associated with RBC traits on chromosome 6p22.1: 26,195 kb – 26,216 kb. <i>HFE</i> (NM_000410) is located from bp 26,195,488 to 26,203,448. Gene structure of <i>HFE</i> is shown.</p>", "links"=>[], "tags"=>["plots", "loci", "rbc", "chromosomes"], "article_id"=>498485, "categories"=>["Genetics", "Medicine", "Hematology"], "users"=>["Iftikhar J. Kullo", "Keyue Ding", "Hayan Jouni", "Carin Y. Smith", "Christopher G. Chute"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0013011.g004", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Regional_plots_of_loci_associated_with_RBC_traits_on_chromosomes_6q23_3_22q12_3_and_6p22_1_/498485", "title"=>"Regional plots of loci associated with RBC traits on chromosomes 6q23.3, 22q12.3, and 6p22.1.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-09-28 02:21:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/827740"], "description"=>"<p>Algorithm for excluding RBC trait values affected by comorbidities, medications, and blood loss.</p>", "links"=>[], "tags"=>["excluding", "rbc", "affected"], "article_id"=>498105, "categories"=>["Genetics", "Medicine", "Hematology"], "users"=>["Iftikhar J. Kullo", "Keyue Ding", "Hayan Jouni", "Carin Y. Smith", "Christopher G. Chute"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0013011.g001", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Algorithm_for_excluding_RBC_trait_values_affected_by_comorbidities_medications_and_blood_loss_/498105", "title"=>"Algorithm for excluding RBC trait values affected by comorbidities, medications, and blood loss.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-09-28 02:15:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/827866"], "description"=>"<p>The horizontal axis shows (–log<sub>10</sub> transformed) expected <i>P</i> values, and the vertical axis indicates (–log<sub>10</sub> transformed) observed <i>P</i> values.</p>", "links"=>[], "tags"=>["plots", "quantitative", "locus"], "article_id"=>498238, "categories"=>["Genetics", "Medicine", "Hematology"], "users"=>["Iftikhar J. Kullo", "Keyue Ding", "Hayan Jouni", "Carin Y. Smith", "Christopher G. Chute"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0013011.g002", "stats"=>{"downloads"=>1, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_QQ_plots_for_quantitative_trait_locus_QTL_analyses_/498238", "title"=>"QQ plots for quantitative trait locus (QTL) analyses.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-09-28 02:17:18"}

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