Genome-Wide Association Study Implicates Chromosome 9q21.31 as a Susceptibility Locus for Asthma in Mexican Children
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{"title"=>"Genome-wide association study implicates chromosome 9q21.31 as a susceptibility locus for asthma in Mexican children", "type"=>"journal", "authors"=>[{"first_name"=>"Dana B.", "last_name"=>"Hancock", "scopus_author_id"=>"14828970000"}, {"first_name"=>"Isabelle", "last_name"=>"Romieu", "scopus_author_id"=>"7006918513"}, {"first_name"=>"Min", "last_name"=>"Shi", "scopus_author_id"=>"35076516000"}, {"first_name"=>"Juan Jose", "last_name"=>"Sienra-Monge", "scopus_author_id"=>"7006418081"}, {"first_name"=>"Hao", "last_name"=>"Wu", "scopus_author_id"=>"55703744600"}, {"first_name"=>"Grace Y.", "last_name"=>"Chiu", "scopus_author_id"=>"10538798700"}, {"first_name"=>"Huiling", "last_name"=>"Li", "scopus_author_id"=>"10538969500"}, {"first_name"=>"Blanca Estela", "last_name"=>"Del Rio-Navarro", "scopus_author_id"=>"7005516194"}, {"first_name"=>"Saffron A.G.", "last_name"=>"Willis-Owens", "scopus_author_id"=>"34874210500"}, {"first_name"=>"Scott T.", "last_name"=>"Weiss", "scopus_author_id"=>"36040917900"}, {"first_name"=>"Benjamin A.", "last_name"=>"Raby", "scopus_author_id"=>"6603864707"}, {"first_name"=>"Hong", "last_name"=>"Gao", "scopus_author_id"=>"56299620000"}, {"first_name"=>"Celeste", "last_name"=>"Eng", "scopus_author_id"=>"7201540466"}, {"first_name"=>"Rocio", "last_name"=>"Chapela", "scopus_author_id"=>"6701766498"}, {"first_name"=>"Esteban G.", "last_name"=>"Burchard", "scopus_author_id"=>"55663704500"}, {"first_name"=>"Hua", "last_name"=>"Tang", "scopus_author_id"=>"56544900000"}, {"first_name"=>"Patrick F.", "last_name"=>"Sullivan", "scopus_author_id"=>"7402033718"}, {"first_name"=>"Stephanie J.", "last_name"=>"London", "scopus_author_id"=>"56988756100"}], "year"=>2009, "source"=>"PLoS Genetics", "identifiers"=>{"sgr"=>"70149094161", "doi"=>"10.1371/journal.pgen.1000623", "pui"=>"355245396", "pmid"=>"19714205", "scopus"=>"2-s2.0-70149094161", "issn"=>"15537390", "isbn"=>"1553-7404 (Electronic)"}, "id"=>"6da4b2a2-f065-336d-b32f-8f733f655498", "abstract"=>"Many candidate genes have been studied for asthma, but replication has varied. Novel candidate genes have been identified for various complex diseases using genome-wide association studies (GWASs). We conducted a GWAS in 492 Mexican children with asthma, predominantly atopic by skin prick test, and their parents using the Illumina HumanHap 550 K BeadChip to identify novel genetic variation for childhood asthma. The 520,767 autosomal single nucleotide polymorphisms (SNPs) passing quality control were tested for association with childhood asthma using log-linear regression with a log-additive risk model. Eleven of the most significantly associated GWAS SNPs were tested for replication in an independent study of 177 Mexican case-parent trios with childhood-onset asthma and atopy using log-linear analysis. The chromosome 9q21.31 SNP rs2378383 (p = 7.10 x 10(-6) in the GWAS), located upstream of transducin-like enhancer of split 4 (TLE4), gave a p-value of 0.03 and the same direction and magnitude of association in the replication study (combined p = 6.79 x 10(-7)). Ancestry analysis on chromosome 9q supported an inverse association between the rs2378383 minor allele (G) and childhood asthma. This work identifies chromosome 9q21.31 as a novel susceptibility locus for childhood asthma in Mexicans. Further, analysis of genome-wide expression data in 51 human tissues from the Novartis Research Foundation showed that median GWAS significance levels for SNPs in genes expressed in the lung differed most significantly from genes not expressed in the lung when compared to 50 other tissues, supporting the biological plausibility of our overall GWAS findings and the multigenic etiology of childhood asthma.", "link"=>"http://www.mendeley.com/research/genomewide-association-study-implicates-chromosome-9q2131-susceptibility-locus-asthma-mexican-childr", "reader_count"=>84, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>8, "Researcher"=>28, "Student > Doctoral Student"=>6, "Student > Ph. D. Student"=>17, "Student > Postgraduate"=>3, "Student > Master"=>14, "Other"=>1, "Student > Bachelor"=>1, "Professor"=>6}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>8, "Researcher"=>28, "Student > Doctoral Student"=>6, "Student > Ph. D. Student"=>17, "Student > Postgraduate"=>3, "Student > Master"=>14, "Other"=>1, "Student > Bachelor"=>1, "Professor"=>6}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>4, "Nursing and Health Professions"=>2, "Mathematics"=>1, "Agricultural and Biological Sciences"=>51, "Medicine and Dentistry"=>16, "Neuroscience"=>1, "Arts and Humanities"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Social Sciences"=>2, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>16}, "Neuroscience"=>{"Neuroscience"=>1}, "Social Sciences"=>{"Social Sciences"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>51}, "Computer Science"=>{"Computer Science"=>1}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>3}, "Environmental Science"=>{"Environmental Science"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "Arts and Humanities"=>{"Arts and Humanities"=>1}}, "reader_count_by_country"=>{"Japan"=>1, "Brazil"=>1, "United Kingdom"=>2}, "group_count"=>4}

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Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/886176"], "description"=>"a<p>SNPs are ranked from smallest to largest GWAS p-value.</p>b<p>Gene names are listed for SNPs mapping within genes. For intergenic SNPs, the nearest genes (upstream, downstream) are listed.</p>c<p>Relative risk for carrying one copy of the minor allele compared to carrying no copies.</p>", "links"=>[], "tags"=>["11", "GWAS", "snps", "trios", "mexican"], "article_id"=>556600, "categories"=>["Genetics", "Medicine", "Infectious Diseases"], "users"=>["Dana B. Hancock", "Isabelle Romieu", "Min Shi", "Juan-Jose Sienra-Monge", "Hao Wu", "Grace Y. Chiu", "Huiling Li", "Blanca Estela del Rio-Navarro", "Saffron A. G. Willis-Owens", "Scott T. Weiss", "Benjamin A. Raby", "Hong Gao", "Celeste Eng", "Rocio Chapela", "Esteban G. Burchard", "Hua Tang", "Patrick F. Sullivan", "Stephanie J. London"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000623.t002", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Replication_testing_for_11_top_GWAS_SNPs_in_an_independent_study_of_case_8211_parent_trios_of_Mexican_ethnicity_/556600", "title"=>"Replication testing for 11 top GWAS SNPs in an independent study of case–parent trios of Mexican ethnicity.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-08-28 01:50:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/885843"], "description"=>"<p>Segregation of Native American ancestry was tested along chromosome 9q21.31, the chromosomal region containing the replicated SNP (rs2378383). A 2,000 SNP window surrounding rs2378383 (located at the vertical blue line) is shown. Data points in red show a significant under- (or over-) transmission of Native American ancestry with |z-score| greater than 1.96, corresponding to an uncorrected p-value of 0.05.</p>", "links"=>[], "tags"=>["ancestry"], "article_id"=>556275, "categories"=>["Genetics", "Medicine", "Infectious Diseases"], "users"=>["Dana B. Hancock", "Isabelle Romieu", "Min Shi", "Juan-Jose Sienra-Monge", "Hao Wu", "Grace Y. Chiu", "Huiling Li", "Blanca Estela del Rio-Navarro", "Saffron A. G. Willis-Owens", "Scott T. Weiss", "Benjamin A. Raby", "Hong Gao", "Celeste Eng", "Rocio Chapela", "Esteban G. Burchard", "Hua Tang", "Patrick F. Sullivan", "Stephanie J. London"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000623.g003", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Chromosome_9q21_31_ancestry_analysis_/556275", "title"=>"Chromosome 9q21.31 ancestry analysis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-08-28 01:44:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/439061", "https://ndownloader.figshare.com/files/439068", "https://ndownloader.figshare.com/files/439078"], "description"=>"<div><p>Many candidate genes have been studied for asthma, but replication has varied. Novel candidate genes have been identified for various complex diseases using genome-wide association studies (GWASs). We conducted a GWAS in 492 Mexican children with asthma, predominantly atopic by skin prick test, and their parents using the Illumina HumanHap 550 K BeadChip to identify novel genetic variation for childhood asthma. The 520,767 autosomal single nucleotide polymorphisms (SNPs) passing quality control were tested for association with childhood asthma using log-linear regression with a log-additive risk model. Eleven of the most significantly associated GWAS SNPs were tested for replication in an independent study of 177 Mexican case–parent trios with childhood-onset asthma and atopy using log-linear analysis. The chromosome 9q21.31 SNP rs2378383 (p = 7.10×10<sup>−6</sup> in the GWAS), located upstream of <em>transducin-like enhancer of split 4 (TLE4)</em>, gave a p-value of 0.03 and the same direction and magnitude of association in the replication study (combined p = 6.79×10<sup>−7</sup>). Ancestry analysis on chromosome 9q supported an inverse association between the rs2378383 minor allele (G) and childhood asthma. This work identifies chromosome 9q21.31 as a novel susceptibility locus for childhood asthma in Mexicans. Further, analysis of genome-wide expression data in 51 human tissues from the Novartis Research Foundation showed that median GWAS significance levels for SNPs in genes expressed in the lung differed most significantly from genes not expressed in the lung when compared to 50 other tissues, supporting the biological plausibility of our overall GWAS findings and the multigenic etiology of childhood asthma.</p></div>", "links"=>[], "tags"=>["genome-wide", "implicates", "chromosome", "susceptibility", "locus", "asthma", "mexican", "children"], "article_id"=>146567, "categories"=>["Genetics", "Medicine", "Cancer"], "users"=>["Dana B. Hancock", "Isabelle Romieu", "Min Shi", "Juan-Jose Sienra-Monge", "Hao Wu", "Grace Y. Chiu", "Huiling Li", "Blanca Estela del Rio-Navarro", "Saffron A. G. Willis-Owens", "Scott T. Weiss", "Benjamin A. Raby", "Hong Gao", "Celeste Eng", "Rocio Chapela", "Esteban G. Burchard", "Hua Tang", "Patrick F. Sullivan", "Stephanie J. London"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1000623.s001", "https://dx.doi.org/10.1371/journal.pgen.1000623.s002", "https://dx.doi.org/10.1371/journal.pgen.1000623.s003"], "stats"=>{"downloads"=>43, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Genome_Wide_Association_Study_Implicates_Chromosome_9q21_31_as_a_Susceptibility_Locus_for_Asthma_in_Mexican_Children/146567", "title"=>"Genome-Wide Association Study Implicates Chromosome 9q21.31 as a Susceptibility Locus for Asthma in Mexican Children", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2009-08-28 01:49:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/885629"], "description"=>"<p>Observed log-linear p-values (black dots) and the corresponding expected log-linear p-values (red line) are plotted on the logarithmic scale for the 520,767 autosomal GWAS SNPs tested for association with childhood asthma.</p>", "links"=>[], "tags"=>["genetics and genomics/complex traits", "genetics and genomics/gene expression", "genetics and genomics/genetics of disease", "respiratory medicine/asthma", "respiratory medicine/respiratory pediatrics"], "article_id"=>556056, "categories"=>["Genetics", "Medicine", "Infectious Diseases"], "users"=>["Dana B. Hancock", "Isabelle Romieu", "Min Shi", "Juan-Jose Sienra-Monge", "Hao Wu", "Grace Y. Chiu", "Huiling Li", "Blanca Estela del Rio-Navarro", "Saffron A. G. Willis-Owens", "Scott T. Weiss", "Benjamin A. Raby", "Hong Gao", "Celeste Eng", "Rocio Chapela", "Esteban G. Burchard", "Hua Tang", "Patrick F. Sullivan", "Stephanie J. London"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000623.g001", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Quantile_quantile_plot_/556056", "title"=>"Quantile-quantile plot.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-08-28 01:40:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/885932"], "description"=>"<p>Genome-wide expression profiles were obtained from publicly available Novartis Research Foundation data, and the gene expression patterns were examined in the context of GWAS results for 14,330 genes. P-values for the Wilcoxon rank-sum test on the logarithmic scale indicate the significance in the difference of median GWAS q-values in genes expressed versus genes not expressed in each of 51 human tissues. Significance thresholds of p<0.01 (solid line) and p<0.05 (dashed line) are shown.</p>", "links"=>[], "tags"=>["findings", "genome-wide"], "article_id"=>556371, "categories"=>["Genetics", "Medicine", "Infectious Diseases"], "users"=>["Dana B. Hancock", "Isabelle Romieu", "Min Shi", "Juan-Jose Sienra-Monge", "Hao Wu", "Grace Y. Chiu", "Huiling Li", "Blanca Estela del Rio-Navarro", "Saffron A. G. Willis-Owens", "Scott T. Weiss", "Benjamin A. Raby", "Hong Gao", "Celeste Eng", "Rocio Chapela", "Esteban G. Burchard", "Hua Tang", "Patrick F. Sullivan", "Stephanie J. London"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000623.g004", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_GWAS_findings_in_the_context_of_genome_wide_expression_/556371", "title"=>"GWAS findings in the context of genome-wide expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-08-28 01:46:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/886109"], "description"=>"a<p>SD, standard deviation.</p>b<p>Numbers do not sum to 492 because of missing data. Percentages are based on non-missing data for each characteristic.</p>", "links"=>[], "tags"=>["characteristics", "492", "children"], "article_id"=>556541, "categories"=>["Genetics", "Medicine", "Infectious Diseases"], "users"=>["Dana B. Hancock", "Isabelle Romieu", "Min Shi", "Juan-Jose Sienra-Monge", "Hao Wu", "Grace Y. Chiu", "Huiling Li", "Blanca Estela del Rio-Navarro", "Saffron A. G. Willis-Owens", "Scott T. Weiss", "Benjamin A. Raby", "Hong Gao", "Celeste Eng", "Rocio Chapela", "Esteban G. Burchard", "Hua Tang", "Patrick F. Sullivan", "Stephanie J. London"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000623.t001", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Demographic_and_clinical_characteristics_of_the_492_children_with_asthma_/556541", "title"=>"Demographic and clinical characteristics of the 492 children with asthma.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-08-28 01:49:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/885706"], "description"=>"<p>Observed log-linear p-values on the logarithmic scale are sorted by physical location on the 22 autosomes for the 520,767 SNPs tested for association with childhood asthma. The 11 of the top 18 SNPs selected for replication are located at or above the solid line (p≤3.3×10<sup>−5</sup>).</p>", "links"=>[], "tags"=>["GWAS"], "article_id"=>556142, "categories"=>["Genetics", "Medicine", "Infectious Diseases"], "users"=>["Dana B. Hancock", "Isabelle Romieu", "Min Shi", "Juan-Jose Sienra-Monge", "Hao Wu", "Grace Y. Chiu", "Huiling Li", "Blanca Estela del Rio-Navarro", "Saffron A. G. Willis-Owens", "Scott T. Weiss", "Benjamin A. Raby", "Hong Gao", "Celeste Eng", "Rocio Chapela", "Esteban G. Burchard", "Hua Tang", "Patrick F. Sullivan", "Stephanie J. London"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000623.g002", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Physical_location_of_GWAS_p_values_/556142", "title"=>"Physical location of GWAS p-values.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-08-28 01:42:22"}

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  • {"unique-ip"=>"15", "full-text"=>"8", "pdf"=>"9", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"3"}
  • {"unique-ip"=>"7", "full-text"=>"9", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"4"}
  • {"unique-ip"=>"8", "full-text"=>"6", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"5"}
  • {"unique-ip"=>"10", "full-text"=>"9", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"6"}

Relative Metric

{"start_date"=>"2009-01-01T00:00:00Z", "end_date"=>"2009-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Computational biology", "average_usage"=>[466, 774, 912, 1013, 1126, 1248, 1346, 1420, 1498, 1603, 1692, 1770, 1842, 1909, 1974, 2041, 2114, 2195, 2268, 2325, 2388, 2456, 2517, 2591, 2643, 2714, 2759, 2840, 2916, 2973, 3015, 3081, 3159, 3222, 3322, 3400, 3480, 3531, 3596, 3665, 3736, 3789, 3872, 3938, 3987, 4050, 4101, 4170, 4279, 4355, 4423, 4468, 4497, 4553, 4595, 4657, 4736, 4785, 4857, 4931, 4999]}, {"subject_area"=>"/Biology and life sciences/Genetics", "average_usage"=>[366, 637, 775, 896, 999, 1118, 1230, 1322, 1416, 1516, 1602, 1685, 1767, 1849, 1914, 1982, 2049, 2120, 2185, 2246, 2303, 2363, 2409, 2473, 2535, 2599, 2655, 2717, 2777, 2842, 2906, 2977, 3021, 3088, 3144, 3199, 3253, 3317, 3379, 3456, 3508, 3567, 3634, 3716, 3781, 3853, 3911, 3974, 4040, 4118, 4170, 4218, 4285, 4341, 4404, 4467, 4527, 4584, 4631, 4689, 4725]}, {"subject_area"=>"/Medicine and health sciences", "average_usage"=>[332, 584, 719, 824, 927, 1030, 1139, 1233, 1322, 1402, 1483, 1570, 1649, 1730, 1806, 1873, 1939, 2003, 2068, 2130, 2191, 2248, 2302, 2362, 2427, 2485, 2544, 2599, 2653, 2709, 2778, 2840, 2896, 2950, 3013, 3073, 3137, 3189, 3253, 3305, 3364, 3423, 3489, 3557, 3606, 3668, 3742, 3797, 3852, 3907, 3962, 4027, 4072, 4132, 4193, 4256, 4308, 4366, 4427, 4493, 4556]}, {"subject_area"=>"/People and places/Population groupings", "average_usage"=>[326, 591, 716, 814, 900, 987, 1120, 1224, 1289, 1374, 1460, 1550, 1643, 1734, 1802, 1864, 1932, 1993, 2048, 2125, 2213, 2285, 2353, 2413, 2485, 2557, 2605, 2660, 2740, 2788, 2845, 2907, 2959, 3036, 3109, 3163, 3228, 3286, 3351, 3404, 3482, 3562, 3633, 3707, 3749, 3842, 3924, 3985, 4080, 4118, 4176, 4261, 4333, 4379, 4458, 4529, 4578, 4632, 4711, 4767, 4817]}]}
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