A Genome-Wide Association Study of Pulmonary Function Measures in the Framingham Heart Study
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{"title"=>"A Genome-Wide Association Study of Pulmonary Function Measures in the Framingham Heart Study", "type"=>"journal", "authors"=>[{"first_name"=>"Jemma B.", "last_name"=>"Wilk"}, {"first_name"=>"Ting-hsu", "last_name"=>"Chen"}, {"first_name"=>"Daniel J.", "last_name"=>"Gottlieb"}, {"first_name"=>"Robert E.", "last_name"=>"Walter"}, {"first_name"=>"Michael W.", "last_name"=>"Nagle"}, {"first_name"=>"Brian J.", "last_name"=>"Brandler"}, {"first_name"=>"Richard H.", "last_name"=>"Myers"}, {"first_name"=>"Ingrid B.", "last_name"=>"Borecki"}, {"first_name"=>"Edwin K.", "last_name"=>"Silverman"}, {"first_name"=>"Scott T.", "last_name"=>"Weiss"}, {"first_name"=>"George T.", "last_name"=>"O'Connor"}], "year"=>2009, "source"=>"PLoS Genetics", "identifiers"=>{"issn"=>"1553-7404", "pmid"=>"19300500", "doi"=>"10.1371/journal.pgen.1000429", "isbn"=>"1553-7404 (Electronic)\\r1553-7390 (Linking)"}, "id"=>"faa0e30c-8fef-3279-925c-5c3710797ad4", "abstract"=>"The ratio of forced expiratory volume in one second to forced vital capacity (FEV(1)/FVC) is a measure used to diagnose airflow obstruction and is highly heritable. We performed a genome-wide association study in 7,691 Framingham Heart Study participants to identify single-nucleotide polymorphisms (SNPs) associated with the FEV(1)/FVC ratio, analyzed as a percent of the predicted value. Identified SNPs were examined in an independent set of 835 Family Heart Study participants enriched for airflow obstruction. Four SNPs in tight linkage disequilibrium on chromosome 4q31 were associated with the percent predicted FEV(1)/FVC ratio with p-values of genome-wide significance in the Framingham sample (best p-value = 3.6e-09). One of the four chromosome 4q31 SNPs (rs13147758; p-value 2.3e-08 in Framingham) was genotyped in the Family Heart Study and produced evidence of association with the same phenotype, percent predicted FEV(1)/FVC (p-value = 2.0e-04). The effect estimates for association in the Framingham and Family Heart studies were in the same direction, with the minor allele (G) associated with higher FEV(1)/FVC ratio levels. Results from the Family Heart Study demonstrated that the association extended to FEV(1) and dichotomous airflow obstruction phenotypes, particularly among smokers. The SNP rs13147758 was associated with the percent predicted FEV(1)/FVC ratio in independent samples from the Framingham and Family Heart Studies producing a combined p-value of 8.3e-11, and this region of chromosome 4 around 145.68 megabases was associated with COPD in three additional populations reported in the accompanying manuscript. The associated SNPs do not lie within a gene transcript but are near the hedgehog-interacting protein (HHIP) gene and several expressed sequence tags cloned from fetal lung. Though it is unclear what gene or regulatory effect explains the association, the region warrants further investigation.", "link"=>"http://www.mendeley.com/research/genomewide-association-study-pulmonary-function-measures-framingham-heart-study-7", "reader_count"=>145, "reader_count_by_academic_status"=>{"Unspecified"=>7, "Professor > Associate Professor"=>12, "Researcher"=>33, "Student > Doctoral Student"=>12, "Student > Ph. D. Student"=>25, "Student > Postgraduate"=>4, "Student > Master"=>17, "Other"=>12, "Student > Bachelor"=>13, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>2, "Professor"=>7}, "reader_count_by_user_role"=>{"Unspecified"=>7, "Professor > Associate Professor"=>12, "Researcher"=>33, "Student > Doctoral Student"=>12, "Student > Ph. D. Student"=>25, "Student > Postgraduate"=>4, "Student > Master"=>17, "Other"=>12, "Student > Bachelor"=>13, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>2, "Professor"=>7}, "reader_count_by_subject_area"=>{"Unspecified"=>10, "Agricultural and Biological Sciences"=>67, "Business, Management and Accounting"=>1, "Chemistry"=>1, "Computer Science"=>3, "Economics, Econometrics and Finance"=>1, "Nursing and Health Professions"=>2, "Biochemistry, Genetics and Molecular Biology"=>15, "Mathematics"=>1, "Medicine and Dentistry"=>39, "Neuroscience"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Psychology"=>2, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>39}, "Psychology"=>{"Psychology"=>2}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>10}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "Chemistry"=>{"Chemistry"=>1}, "Neuroscience"=>{"Neuroscience"=>1}, "Economics, Econometrics and Finance"=>{"Economics, Econometrics and Finance"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>67}, "Computer Science"=>{"Computer Science"=>3}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>15}}, "reader_count_by_country"=>{"Canada"=>2, "Netherlands"=>1, "Austria"=>1, "Sweden"=>1, "United States"=>7, "Japan"=>1, "United Kingdom"=>2, "Spain"=>3}, "group_count"=>4}

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  • {"files"=>["https://ndownloader.figshare.com/files/904499"], "description"=>"<p>X-axis is the physical position in kb with arrows denoting genes and expressed sequence tags in the region, the left y-axis plots the −log(p-value), and the right y-axis plots the CEPH recombination rate. The blue diamond identifies the labeled SNP of interest, and LD with the SNP is depicted by color of additional diamonds: red-strong LD (r<sup>2</sup>≥0.8), orange-moderate LD (0.5≤r<sup>2</sup><0.8), yellow-low LD (0.2≤r<sup>2</sup><0.5), white-no LD (r<sup>2</sup><0.2).</p>", "links"=>[], "tags"=>["chromosome", "percent", "imputed", "framingham"], "article_id"=>574945, "categories"=>["Genetics", "Plant Biology"], "users"=>["Jemma B. Wilk", "Ting-hsu Chen", "Daniel J. Gottlieb", "Robert E. Walter", "Michael W. Nagle", "Brian J. Brandler", "Richard H. Myers", "Ingrid B. Borecki", "Edwin K. Silverman", "Scott T. Weiss", "George T. O'Connor"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000429.g002", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Plot_of_chromosome_4_association_with_percent_predicted_FEV_1_FVC_in_imputed_Framingham_Heart_Study_data_/574945", "title"=>"Plot of chromosome 4 association with percent predicted FEV<sub>1</sub>/FVC in imputed Framingham Heart Study data.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-03-20 01:22:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/904562"], "description"=>"(a)<p>N = 185 cases, 226 controls.</p>(b)<p>SNP had the lowest p-value for FEV<sub>1</sub> (p = 1.7E-04) in Framingham results for this region.</p>", "links"=>[], "tags"=>["smokers", "chromosome"], "article_id"=>575010, "categories"=>["Genetics", "Plant Biology"], "users"=>["Jemma B. Wilk", "Ting-hsu Chen", "Daniel J. Gottlieb", "Robert E. Walter", "Michael W. Nagle", "Brian J. Brandler", "Richard H. Myers", "Ingrid B. Borecki", "Edwin K. Silverman", "Scott T. Weiss", "George T. O'Connor"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000429.t004", "stats"=>{"downloads"=>7, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_SNP_association_results_for_the_Family_Heart_Study_smokers_N_8202_8202_485_in_the_chromosome_4_region_/575010", "title"=>"SNP association results for the Family Heart Study smokers (N = 485) in the chromosome 4 region.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-03-20 01:23:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/904659"], "description"=>"*<p>Pack-year mean and standard deviation computed among former and current smokers only.</p>", "links"=>[], "tags"=>["characteristics", "framingham"], "article_id"=>575110, "categories"=>["Genetics", "Plant Biology"], "users"=>["Jemma B. Wilk", "Ting-hsu Chen", "Daniel J. Gottlieb", "Robert E. Walter", "Michael W. Nagle", "Brian J. Brandler", "Richard H. Myers", "Ingrid B. Borecki", "Edwin K. Silverman", "Scott T. Weiss", "George T. O'Connor"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000429.t001", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Descriptive_characteristics_of_the_Framingham_and_Family_Heart_Study_participants_/575110", "title"=>"Descriptive characteristics of the Framingham and Family Heart Study participants.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-03-20 01:25:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/447130"], "description"=>"<div><p>The ratio of forced expiratory volume in one second to forced vital capacity (FEV<sub>1</sub>/FVC) is a measure used to diagnose airflow obstruction and is highly heritable. We performed a genome-wide association study in 7,691 Framingham Heart Study participants to identify single-nucleotide polymorphisms (SNPs) associated with the FEV<sub>1</sub>/FVC ratio, analyzed as a percent of the predicted value. Identified SNPs were examined in an independent set of 835 Family Heart Study participants enriched for airflow obstruction. Four SNPs in tight linkage disequilibrium on chromosome 4q31 were associated with the percent predicted FEV<sub>1</sub>/FVC ratio with <em>p</em>-values of genome-wide significance in the Framingham sample (best <em>p</em>-value = 3.6e-09). One of the four chromosome 4q31 SNPs (rs13147758; <em>p</em>-value 2.3e-08 in Framingham) was genotyped in the Family Heart Study and produced evidence of association with the same phenotype, percent predicted FEV<sub>1</sub>/FVC (<em>p</em>-value = 2.0e-04). The effect estimates for association in the Framingham and Family Heart studies were in the same direction, with the minor allele (G) associated with higher FEV<sub>1</sub>/FVC ratio levels. Results from the Family Heart Study demonstrated that the association extended to FEV<sub>1</sub> and dichotomous airflow obstruction phenotypes, particularly among smokers. The SNP rs13147758 was associated with the percent predicted FEV<sub>1</sub>/FVC ratio in independent samples from the Framingham and Family Heart Studies producing a combined <em>p</em>-value of 8.3e-11, and this region of chromosome 4 around 145.68 megabases was associated with COPD in three additional populations reported in the accompanying manuscript. The associated SNPs do not lie within a gene transcript but are near the hedgehog-interacting protein (<em>HHIP</em>) gene and several expressed sequence tags cloned from fetal lung. Though it is unclear what gene or regulatory effect explains the association, the region warrants further investigation.</p></div>", "links"=>[], "tags"=>["genome-wide", "pulmonary", "measures", "framingham"], "article_id"=>148139, "categories"=>["Genetics", "Cell Biology"], "users"=>["Jemma B. Wilk", "Ting-hsu Chen", "Daniel J. Gottlieb", "Robert E. Walter", "Michael W. Nagle", "Brian J. Brandler", "Richard H. Myers", "Ingrid B. Borecki", "Edwin K. Silverman", "Scott T. Weiss", "George T. O'Connor"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000429", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/A_Genome_Wide_Association_Study_of_Pulmonary_Function_Measures_in_the_Framingham_Heart_Study/148139", "title"=>"A Genome-Wide Association Study of Pulmonary Function Measures in the Framingham Heart Study", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-03-20 02:15:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/904407"], "description"=>"<p>Quantile-Quantile Plot of GWA results for percent predicted FEV<sub>1</sub>/FVC.</p>", "links"=>[], "tags"=>["gwa", "percent"], "article_id"=>574860, "categories"=>["Genetics", "Plant Biology"], "users"=>["Jemma B. Wilk", "Ting-hsu Chen", "Daniel J. Gottlieb", "Robert E. Walter", "Michael W. Nagle", "Brian J. Brandler", "Richard H. Myers", "Ingrid B. Borecki", "Edwin K. Silverman", "Scott T. Weiss", "George T. O'Connor"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000429.g001", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Quantile_Quantile_Plot_of_GWA_results_for_percent_predicted_FEV_1_FVC_/574860", "title"=>"Quantile-Quantile Plot of GWA results for percent predicted FEV<sub>1</sub>/FVC.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-03-20 01:21:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/904611"], "description"=>"<p>Association results for rs13147758 with percent predicted FEV<sub>1</sub>/FVC, FEV<sub>1</sub>, and airflow obstruction across studies and in subset of ever smokers.</p>", "links"=>[], "tags"=>["rs13147758", "percent", "airflow", "obstruction", "studies", "subset"], "article_id"=>575056, "categories"=>["Genetics", "Plant Biology"], "users"=>["Jemma B. Wilk", "Ting-hsu Chen", "Daniel J. Gottlieb", "Robert E. Walter", "Michael W. Nagle", "Brian J. Brandler", "Richard H. Myers", "Ingrid B. Borecki", "Edwin K. Silverman", "Scott T. Weiss", "George T. O'Connor"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000429.t005", "stats"=>{"downloads"=>4, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Association_results_for_rs13147758_with_percent_predicted_FEV_1_FVC_FEV_1_and_airflow_obstruction_across_studies_and_in_subset_of_ever_smokers_/575056", "title"=>"Association results for rs13147758 with percent predicted FEV<sub>1</sub>/FVC, FEV<sub>1</sub>, and airflow obstruction across studies and in subset of ever smokers.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-03-20 01:24:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/904788"], "description"=>"*<p>SNP was genotyped and found to be non-polymorphic in the sample.</p>", "links"=>[], "tags"=>["snps", "10", "gwa", "regions", "framingham", "examined", "835", "percent"], "article_id"=>575220, "categories"=>["Genetics", "Plant Biology"], "users"=>["Jemma B. Wilk", "Ting-hsu Chen", "Daniel J. Gottlieb", "Robert E. Walter", "Michael W. Nagle", "Brian J. Brandler", "Richard H. Myers", "Ingrid B. Borecki", "Edwin K. Silverman", "Scott T. Weiss", "George T. O'Connor"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000429.t003", "stats"=>{"downloads"=>2, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Association_results_for_SNPs_in_the_top_10_GWA_regions_identified_in_Framingham_and_examined_in_835_Family_Heart_Study_participants_for_association_to_percent_predicted_FEV_1_FVC_/575220", "title"=>"Association results for SNPs in the top 10 GWA regions identified in Framingham and examined in 835 Family Heart Study participants for association to percent predicted FEV<sub>1</sub>/FVC.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-03-20 01:27:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/904720"], "description"=>"*<p>The direction of effect indicated by the sign of the FBAT Z score was consistent with the direction of the LME beta estimate for all SNPs.</p>", "links"=>[], "tags"=>["10", "regions", "implicated", "lme", "percent", "additive", "studying", "genotyped", "snps", "framingham"], "article_id"=>575161, "categories"=>["Genetics", "Plant Biology"], "users"=>["Jemma B. Wilk", "Ting-hsu Chen", "Daniel J. Gottlieb", "Robert E. Walter", "Michael W. Nagle", "Brian J. Brandler", "Richard H. Myers", "Ingrid B. Borecki", "Edwin K. Silverman", "Scott T. Weiss", "George T. O'Connor"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000429.t002", "stats"=>{"downloads"=>3, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Top_10_regions_implicated_by_LME_results_for_percent_predicted_FEV_1_FVC_in_an_additive_genetic_model_studying_genotyped_SNPs_in_the_Framingham_Heart_Study_/575161", "title"=>"Top 10 regions implicated by LME results for percent predicted FEV<sub>1</sub>/FVC in an additive genetic model studying genotyped SNPs in the Framingham Heart Study.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-03-20 01:26:01"}

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  • {"unique-ip"=>"10", "full-text"=>"9", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
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  • {"unique-ip"=>"10", "full-text"=>"10", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"1"}
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  • {"unique-ip"=>"16", "full-text"=>"17", "pdf"=>"9", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"12", "full-text"=>"13", "pdf"=>"8", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
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  • {"unique-ip"=>"10", "full-text"=>"7", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"9", "full-text"=>"7", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"11", "full-text"=>"9", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"15", "full-text"=>"14", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"11", "full-text"=>"9", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"11", "full-text"=>"8", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
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Relative Metric

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