Mapping Genetic Variants Associated with Beta-Adrenergic Responses in Inbred Mice
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Mendeley | Further Information

{"title"=>"Mapping genetic variants associated with beta-adrenergic responses in inbred mice", "type"=>"journal", "authors"=>[{"first_name"=>"Micha", "last_name"=>"Hersch", "scopus_author_id"=>"13106002300"}, {"first_name"=>"Bastian", "last_name"=>"Peter", "scopus_author_id"=>"14120070500"}, {"first_name"=>"Hyun Min", "last_name"=>"Kang", "scopus_author_id"=>"9739748700"}, {"first_name"=>"Fanny", "last_name"=>"Schüpfer", "scopus_author_id"=>"16305432700"}, {"first_name"=>"Hugues", "last_name"=>"Abriel", "scopus_author_id"=>"6701801243"}, {"first_name"=>"Thierry", "last_name"=>"Pedrazzini", "scopus_author_id"=>"7004689595"}, {"first_name"=>"Eleazar", "last_name"=>"Eskin", "scopus_author_id"=>"7003344359"}, {"first_name"=>"Jacques S.", "last_name"=>"Beckmann", "scopus_author_id"=>"55817551915"}, {"first_name"=>"Sven", "last_name"=>"Bergmann", "scopus_author_id"=>"7101828386"}, {"first_name"=>"Fabienne", "last_name"=>"Maurer", "scopus_author_id"=>"7102330985"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"365351851", "sgr"=>"84864435040", "issn"=>"19326203", "pmid"=>"22859963", "scopus"=>"2-s2.0-84864435040", "doi"=>"10.1371/journal.pone.0041032", "isbn"=>"3100001125"}, "id"=>"3bd807da-7ec4-3c7b-9501-0c350478201a", "abstract"=>"β-blockers and β-agonists are primarily used to treat cardiovascular diseases. Inter-individual variability in response to both drug classes is well recognized, yet the identity and relative contribution of the genetic players involved are poorly understood. This work is the first genome-wide association study (GWAS) addressing the values and susceptibility of cardiovascular-related traits to a selective β(1)-blocker, Atenolol (ate), and a β-agonist, Isoproterenol (iso). The phenotypic dataset consisted of 27 highly heritable traits, each measured across 22 inbred mouse strains and four pharmacological conditions. The genotypic panel comprised 79922 informative SNPs of the mouse HapMap resource. Associations were mapped by Efficient Mixed Model Association (EMMA), a method that corrects for the population structure and genetic relatedness of the various strains. A total of 205 separate genome-wide scans were analyzed. The most significant hits include three candidate loci related to cardiac and body weight, three loci for electrocardiographic (ECG) values, two loci for the susceptibility of atrial weight index to iso, four loci for the susceptibility of systolic blood pressure (SBP) to perturbations of the β-adrenergic system, and one locus for the responsiveness of QTc (p<10(-8)). An additional 60 loci were suggestive for one or the other of the 27 traits, while 46 others were suggestive for one or the other drug effects (p<10(-6)). Most hits tagged unexpected regions, yet at least two loci for the susceptibility of SBP to β-adrenergic drugs pointed at members of the hypothalamic-pituitary-thyroid axis. Loci for cardiac-related traits were preferentially enriched in genes expressed in the heart, while 23% of the testable loci were replicated with datasets of the Mouse Phenome Database (MPD). Altogether these data and validation tests indicate that the mapped loci are relevant to the traits and responses studied.", "link"=>"http://www.mendeley.com/research/mapping-genetic-variants-associated-betaadrenergic-responses-inbred-mice-1", "reader_count"=>20, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Student > Doctoral Student"=>1, "Researcher"=>4, "Student > Ph. D. Student"=>5, "Student > Master"=>1, "Other"=>1, "Student > Bachelor"=>1, "Professor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Student > Doctoral Student"=>1, "Researcher"=>4, "Student > Ph. D. Student"=>5, "Student > Master"=>1, "Other"=>1, "Student > Bachelor"=>1, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>11, "Medicine and Dentistry"=>3, "Arts and Humanities"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>11}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>2}, "Arts and Humanities"=>{"Arts and Humanities"=>1}}, "reader_count_by_country"=>{"Canada"=>1, "United States"=>1, "United Kingdom"=>1, "Switzerland"=>2}, "group_count"=>2}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/598475"], "description"=>"<p>A. Composite Manhattan plot superimposing the four EMMA scans for non-adjusted AW. Association scores (-log<sub>10 </sub><i>p</i>-value; y-axis) are shown for each chromosomal position (x-axis) tested by EMMA. Suggestive and significant thresholds of association are indicated by orange and red lines, respectively. B. QQ-plots reporting the -log<sub>10</sub> of <i>p</i>-values as obtained by EMMA. The null hypothesis (<i>H<sub>0</sub></i>) is indicated by the dotted line. A strong upper deviation from this line in the region of the lowest <i>p</i>-values is indicative of a true association. C, D. Zoom-in on loci 1 and 2. Genes are displayed as indicated in the NCBI37/mm9 assembly of the UCSC genome browser <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0041032#pone.0041032-Fujita1\" target=\"_blank\">[86]</a>.</p>", "links"=>[], "tags"=>["non-adjusted"], "article_id"=>268960, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Micha Hersch", "Bastian Peter", "Hyun Min Kang", "Fanny Schüpfer", "Hugues Abriel", "Thierry Pedrazzini", "Eleazar Eskin", "Jacques S. Beckmann", "Sven Bergmann", "Fabienne Maurer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0041032.g002", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_GWAS_of_non_adjusted_AW_/268960", "title"=>"GWAS of non-adjusted AW.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-07-31 02:29:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/598768"], "description"=>"<p>For each trait listed, the suggestive hits mapped by EMMA were tested using the indicated replication dataset (RD) of the MPD. RD ID: MPD ID number of the trait considered for the replication test; RD strains in EMMA: number of strains of the RD used in EMMA; strains in common: number of strains in common between this study and the RD.</p>", "links"=>[], "tags"=>["genetics and genomics", "Computational biology"], "article_id"=>269257, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Micha Hersch", "Bastian Peter", "Hyun Min Kang", "Fanny Schüpfer", "Hugues Abriel", "Thierry Pedrazzini", "Eleazar Eskin", "Jacques S. Beckmann", "Sven Bergmann", "Fabienne Maurer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0041032.t003", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Replication_studies_/269257", "title"=>"Replication studies.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-07-31 02:34:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/598734"], "description"=>"<p>See <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0041032#pone-0041032-t001\" target=\"_blank\">Table 1</a> for the details of the abbreviations.</p>", "links"=>[], "tags"=>["hits", "approximated"], "article_id"=>269224, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Micha Hersch", "Bastian Peter", "Hyun Min Kang", "Fanny Schüpfer", "Hugues Abriel", "Thierry Pedrazzini", "Eleazar Eskin", "Jacques S. Beckmann", "Sven Bergmann", "Fabienne Maurer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0041032.t002", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Top_hits_for_the_set_of_approximated_drug_effects_/269224", "title"=>"Top hits for the set of approximated drug effects.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-07-31 02:33:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/598379"], "description"=>"<p>The genetic maps of twelve loci are presented. Chromosomal positions are given on the vertical axis (in Mb). Colored boxes are used to differentiate contiguous genes. The “trait plus treatment” combinations producing the strongest associations are indicated in each plot’s title. The positions of the significant and suggestive hits are indicated by red and orange arrows, respectively (all hits are detailed in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0041032#pone.0041032.s014\" target=\"_blank\">Table S3</a>). Potential overlaps linking these loci with independent evidence obtained from functional or genetic studies performed in mice, humans and rats are annotated in the respective vertical tracks (see main text for details). For instance, variants of <i>ADAMTS3</i> are associated with human height (locus 1). Overlaps with rat QTLs are indicated at the bottom of the maps for loci 1, 2 and 33. DBP: diastolic blood pressure; MI: myocardial infarction; DCM: dilated cardiomyopathy; LVH: left ventricular hypertrophy; CVD: cardiovascular disease.</p>", "links"=>[], "tags"=>["maps", "loci", "cardiovascular-related"], "article_id"=>268861, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Micha Hersch", "Bastian Peter", "Hyun Min Kang", "Fanny Schüpfer", "Hugues Abriel", "Thierry Pedrazzini", "Eleazar Eskin", "Jacques S. Beckmann", "Sven Bergmann", "Fabienne Maurer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0041032.g001", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Synoptic_maps_of_the_top_loci_for_cardiovascular_related_traits_/268861", "title"=>"Synoptic maps of the top loci for cardiovascular-related traits.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-07-31 02:27:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/598588"], "description"=>"<p>The genetic maps of eight loci are presented and annotated as described in the legend of <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0041032#pone-0041032-g001\" target=\"_blank\">Figure 1</a>. CHF: congestive heart failure; AF: atrial fibrillation; LQTS: long QT syndrome.</p>", "links"=>[], "tags"=>["maps", "loci"], "article_id"=>269078, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Micha Hersch", "Bastian Peter", "Hyun Min Kang", "Fanny Schüpfer", "Hugues Abriel", "Thierry Pedrazzini", "Eleazar Eskin", "Jacques S. Beckmann", "Sven Bergmann", "Fabienne Maurer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0041032.g003", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Synoptic_maps_of_the_top_loci_associated_with_the_effects_of_iso_and_ate_/269078", "title"=>"Synoptic maps of the top loci associated with the effects of <i>iso</i> and <i>ate</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-07-31 02:31:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/316141", "https://ndownloader.figshare.com/files/316269", "https://ndownloader.figshare.com/files/316319", "https://ndownloader.figshare.com/files/316368", "https://ndownloader.figshare.com/files/316395", "https://ndownloader.figshare.com/files/316415", "https://ndownloader.figshare.com/files/316447", "https://ndownloader.figshare.com/files/316461", "https://ndownloader.figshare.com/files/316474", "https://ndownloader.figshare.com/files/316479", "https://ndownloader.figshare.com/files/316484", "https://ndownloader.figshare.com/files/316488", "https://ndownloader.figshare.com/files/316491", "https://ndownloader.figshare.com/files/316492", "https://ndownloader.figshare.com/files/316494", "https://ndownloader.figshare.com/files/316498"], "description"=>"<div><p><em>β</em>-blockers and <em>β</em>-agonists are primarily used to treat cardiovascular diseases. Inter-individual variability in response to both drug classes is well recognized, yet the identity and relative contribution of the genetic players involved are poorly understood. This work is the first genome-wide association study (GWAS) addressing the values and susceptibility of cardiovascular-related traits to a selective <em>β</em><sub>1</sub>-blocker, Atenolol (<em>ate</em>), and a <em>β</em>-agonist, Isoproterenol (<em>iso</em>). The phenotypic dataset consisted of 27 highly heritable traits, each measured across 22 inbred mouse strains and four pharmacological conditions. The genotypic panel comprised 79922 informative SNPs of the mouse HapMap resource. Associations were mapped by Efficient Mixed Model Association (EMMA), a method that corrects for the population structure and genetic relatedness of the various strains. A total of 205 separate genome-wide scans were analyzed. The most significant hits include three candidate loci related to cardiac and body weight, three loci for electrocardiographic (ECG) values, two loci for the susceptibility of atrial weight index to <em>iso</em>, four loci for the susceptibility of systolic blood pressure (SBP) to perturbations of the <em>β</em>-adrenergic system, and one locus for the responsiveness of QTc (<em>p</em><10<sup>−8</sup>). An additional 60 loci were suggestive for one or the other of the 27 traits, while 46 others were suggestive for one or the other drug effects (<em>p</em><10<sup>−6</sup>). Most hits tagged unexpected regions, yet at least two loci for the susceptibility of SBP to <em>β</em>-adrenergic drugs pointed at members of the hypothalamic-pituitary-thyroid axis. Loci for cardiac-related traits were preferentially enriched in genes expressed in the heart, while 23% of the testable loci were replicated with datasets of the Mouse Phenome Database (MPD). Altogether these data and validation tests indicate that the mapped loci are relevant to the traits and responses studied.</p> </div>", "links"=>[], "tags"=>["variants", "responses", "inbred", "mice"], "article_id"=>122387, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Micha Hersch", "Bastian Peter", "Hyun Min Kang", "Fanny Schüpfer", "Hugues Abriel", "Thierry Pedrazzini", "Eleazar Eskin", "Jacques S. Beckmann", "Sven Bergmann", "Fabienne Maurer"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0041032.s001", "https://dx.doi.org/10.1371/journal.pone.0041032.s002", "https://dx.doi.org/10.1371/journal.pone.0041032.s003", "https://dx.doi.org/10.1371/journal.pone.0041032.s004", "https://dx.doi.org/10.1371/journal.pone.0041032.s005", "https://dx.doi.org/10.1371/journal.pone.0041032.s006", "https://dx.doi.org/10.1371/journal.pone.0041032.s007", "https://dx.doi.org/10.1371/journal.pone.0041032.s008", "https://dx.doi.org/10.1371/journal.pone.0041032.s009", "https://dx.doi.org/10.1371/journal.pone.0041032.s010", "https://dx.doi.org/10.1371/journal.pone.0041032.s011", "https://dx.doi.org/10.1371/journal.pone.0041032.s012", "https://dx.doi.org/10.1371/journal.pone.0041032.s013", "https://dx.doi.org/10.1371/journal.pone.0041032.s014", "https://dx.doi.org/10.1371/journal.pone.0041032.s015", "https://dx.doi.org/10.1371/journal.pone.0041032.s016"], "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Mapping_Genetic_Variants_Associated_with_Beta_Adrenergic_Responses_in_Inbred_Mice/122387", "title"=>"Mapping Genetic Variants Associated with <em>Beta</em>-Adrenergic Responses in Inbred Mice", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-07-31 00:39:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/598701"], "description"=>"<p>For each locus, the <i>p</i>-value of the most significant hit is given as calculated in EMMA. Scores are highlighted in bold letters when they were obtained at SNPs with fully documented allelic information. When this information was incomplete, the corrected score was imputed manually (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0041032#s4\" target=\"_blank\">Material and Method</a>s). Corr. Effect size: effect size at the surrogate SNP used for imputation; *: loci 4 and 6 share identical SDPs on separate chromosomes; <sup>#</sup>: the SDP of locus 7 is compatible with that of suggestive locus 32 for the same trait (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0041032#pone.0041032.s014\" target=\"_blank\">Table S3</a>); bpm: beats per min; nf: not found.</p>", "links"=>[], "tags"=>["hits", "27", "cardiovascular-related"], "article_id"=>269188, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Micha Hersch", "Bastian Peter", "Hyun Min Kang", "Fanny Schüpfer", "Hugues Abriel", "Thierry Pedrazzini", "Eleazar Eskin", "Jacques S. Beckmann", "Sven Bergmann", "Fabienne Maurer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0041032.t001", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Top_hits_for_the_set_of_27_cardiovascular_related_traits_/269188", "title"=>"Top hits for the set of 27 cardiovascular-related traits.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-07-31 02:33:08"}

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Relative Metric

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