Genome-Wide Association Study of Maternal and Inherited Loci for Conotruncal Heart Defects
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{"title"=>"Genome-wide association study of maternal and inherited loci for conotruncal heart defects", "type"=>"journal", "authors"=>[{"first_name"=>"A. J.", "last_name"=>"Agopian", "scopus_author_id"=>"35309352000"}, {"first_name"=>"Laura E.", "last_name"=>"Mitchell", "scopus_author_id"=>"7203039016"}, {"first_name"=>"Joseph", "last_name"=>"Glessner", "scopus_author_id"=>"17345446300"}, {"first_name"=>"Angela D.", "last_name"=>"Bhalla", "scopus_author_id"=>"55889661000"}, {"first_name"=>"Anshuman", "last_name"=>"Sewda", "scopus_author_id"=>"55807737300"}, {"first_name"=>"Hakon", "last_name"=>"Hakonarson", "scopus_author_id"=>"55531171800"}, {"first_name"=>"Elizabeth", "last_name"=>"Goldmuntz", "scopus_author_id"=>"7003634031"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84900400677", "sgr"=>"84900400677", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0096057", "pmid"=>"24800985", "isbn"=>"1932-6203", "pui"=>"373074648"}, "id"=>"5d4e01b8-859f-34be-bac3-cfaf08292c5c", "abstract"=>"Conotruncal and related heart defects (CTDs) are a group of serious and relatively common birth defects. Although both maternal and inherited genotypes are thought to play a role in the etiology of CTDs, few specific genetic risk factors have been identified. To determine whether common variants acting through the genotype of the mother (e.g. via an in utero effect) or the case are associated with CTDs, we conducted a genome-wide association study of 750 CTD case-parent triads, with follow-up analyses in 358 independent triads. Log-linear analyses were used to assess the association of CTDs with the genotypes of both the mother and case. No association achieved genomewide significance in either the discovery or combined (discovery+follow-up) samples. However, three loci with p-values suggestive of association (p<10-5) in the discovery sample had p-values <0.05 in the follow-up sample and p-values in the combined data that were lower than in the discovery sample. These included suggestive association with an inherited intergenic variant at 20p12.3 (rs6140038, combined p = 1.0 × 10(-5)) and an inherited intronic variant in KCNJ4 at 22q13.1 (rs2267386, combined p = 9.8 × 10(-6)), as well as with a maternal variant in SLC22A24 at 11q12.3 (rs11231379, combined p = 4.2 × 10(-6)). These observations suggest novel candidate loci for CTDs, including loci that appear to be associated with the risk of CTDs via the maternal genotype, but further studies are needed to confirm these associations.", "link"=>"http://www.mendeley.com/research/genomewide-association-study-maternal-inherited-loci-conotruncal-heart-defects", "reader_count"=>14, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>5, "Student > Ph. D. Student"=>3, "Other"=>1, "Student > Master"=>2, "Student > Bachelor"=>2}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>5, "Student > Ph. D. Student"=>3, "Other"=>1, "Student > Master"=>2, "Student > Bachelor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>2, "Mathematics"=>1, "Medicine and Dentistry"=>4, "Agricultural and Biological Sciences"=>4, "Social Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Social Sciences"=>{"Social Sciences"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>4}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"United Kingdom"=>1}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1487114"], "description"=>"A<p>Chromosome.</p>B<p>Hg18/NCBI build 36.</p>C<p>Minor allele frequency among non-Hispanic white study participant founders (i.e. mother and father).</p>D<p>For SNPs mapping within genes, gene names are listed, and for intergenic SNPs, the nearest gene is listed in parentheses.</p>E<p>Relative risk estimate for carrying one copy of the high-risk allele compared to no copies, and corresponding 95% confidence interval.</p>F<p>Imputed SNP; concordance between the imputed and assay-based genotypes in 21 samples from the discovery sample that were genotyped with the follow-up sample was 98.5%.</p>", "links"=>[], "tags"=>["anatomy", "Cardiovascular anatomy", "Computational biology", "genome analysis", "Genome-wide association studies", "developmental biology", "morphogenesis", "Birth defects", "Congenital heart defects", "genetics", "Heredity", "Human genetics", "Population biology", "Population metrics", "Death rates", "epidemiology", "Genetic epidemiology", "variants", "suggestive", "inherited", "maternal", "conotruncal"], "article_id"=>1018133, "categories"=>["Biological Sciences"], "users"=>["A. J. Agopian", "Laura E. Mitchell", "Joseph Glessner", "Angela D. Bhalla", "Anshuman Sewda", "Hakon Hakonarson", "Elizabeth Goldmuntz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0096057.t002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_data_for_top_variants_with_suggestive_inherited_or_maternal_association_with_conotruncal_heart_defects_/1018133", "title"=>"Summary data for top variants with suggestive inherited or maternal association with conotruncal heart defects.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-05-06 03:35:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/1487112"], "description"=>"<p>A) SNPs in <i>SLC22A24</i> B) SNPs near <i>FHIT</i> C) rs2267386 D) rs6140038. Each pane shows the log-linear model association statistic (−log<sub>10</sub> p) on the left y axis for the discovery sample variant with the highest regional value that was confirmed in our follow-up sample (purple diamond) and nearby markers (circles). Linkage disequilibrium (r<sup>2</sup>) between this variant and nearby markers is indicated by red shading and recombination rates across each region in 1000 Genomes CEU data are indicated by blue lines on the right y axis. The position on the chromosome (hg18) and the position of nearby genes is shown on the x-axis.</p>", "links"=>[], "tags"=>["anatomy", "Cardiovascular anatomy", "Computational biology", "genome analysis", "Genome-wide association studies", "developmental biology", "morphogenesis", "Birth defects", "Congenital heart defects", "genetics", "Heredity", "Human genetics", "Population biology", "Population metrics", "Death rates", "epidemiology", "Genetic epidemiology", "suggestive", "associations", "conotruncal", "malformations"], "article_id"=>1018131, "categories"=>["Biological Sciences"], "users"=>["A. J. Agopian", "Laura E. Mitchell", "Joseph Glessner", "Angela D. Bhalla", "Anshuman Sewda", "Hakon Hakonarson", "Elizabeth Goldmuntz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0096057.g001", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Loci_showing_suggestive_associations_with_conotruncal_malformations_in_the_discovery_sample_/1018131", "title"=>"Loci showing suggestive associations with conotruncal malformations in the discovery sample.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-05-06 03:35:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/1487113"], "description"=>"A<p>Includes conoventricular, posterior malalignment and conoseptal hypoplasia.</p>", "links"=>[], "tags"=>["anatomy", "Cardiovascular anatomy", "Computational biology", "genome analysis", "Genome-wide association studies", "developmental biology", "morphogenesis", "Birth defects", "Congenital heart defects", "genetics", "Heredity", "Human genetics", "Population biology", "Population metrics", "Death rates", "epidemiology", "Genetic epidemiology", "cases", "conotruncal"], "article_id"=>1018132, "categories"=>["Biological Sciences"], "users"=>["A. J. Agopian", "Laura E. Mitchell", "Joseph Glessner", "Angela D. Bhalla", "Anshuman Sewda", "Hakon Hakonarson", "Elizabeth Goldmuntz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0096057.t001", "stats"=>{"downloads"=>3, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Characteristics_of_cases_with_conotruncal_and_related_heart_defects_/1018132", "title"=>"Characteristics of cases with conotruncal and related heart defects.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-05-06 03:35:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/1487116", "https://ndownloader.figshare.com/files/1487117", "https://ndownloader.figshare.com/files/1487118"], "description"=>"<div><p>Conotruncal and related heart defects (CTDs) are a group of serious and relatively common birth defects. Although both maternal and inherited genotypes are thought to play a role in the etiology of CTDs, few specific genetic risk factors have been identified. To determine whether common variants acting through the genotype of the mother (e.g. via an in utero effect) or the case are associated with CTDs, we conducted a genome-wide association study of 750 CTD case-parent triads, with follow-up analyses in 358 independent triads. Log-linear analyses were used to assess the association of CTDs with the genotypes of both the mother and case. No association achieved genomewide significance in either the discovery or combined (discovery+follow-up) samples. However, three loci with p-values suggestive of association (p<10<sup>−5</sup>) in the discovery sample had p-values <0.05 in the follow-up sample and p-values in the combined data that were lower than in the discovery sample. These included suggestive association with an inherited intergenic variant at 20p12.3 (rs6140038, combined p = 1.0×10<sup>−5</sup>) and an inherited intronic variant in <i>KCNJ4</i> at 22q13.1 (rs2267386, combined p = 9.8×10<sup>−6</sup>), as well as with a maternal variant in <i>SLC22A24</i> at 11q12.3 (rs11231379, combined p = 4.2×10<sup>−6</sup>). These observations suggest novel candidate loci for CTDs, including loci that appear to be associated with the risk of CTDs via the maternal genotype, but further studies are needed to confirm these associations.</p></div>", "links"=>[], "tags"=>["anatomy", "Cardiovascular anatomy", "Computational biology", "genome analysis", "Genome-wide association studies", "developmental biology", "morphogenesis", "Birth defects", "Congenital heart defects", "genetics", "Heredity", "Human genetics", "Population biology", "Population metrics", "Death rates", "epidemiology", "Genetic epidemiology", "maternal", "inherited", "loci", "conotruncal"], "article_id"=>1018135, "categories"=>["Biological Sciences"], "users"=>["A. J. Agopian", "Laura E. Mitchell", "Joseph Glessner", "Angela D. Bhalla", "Anshuman Sewda", "Hakon Hakonarson", "Elizabeth Goldmuntz"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0096057.s001", "https://dx.doi.org/10.1371/journal.pone.0096057.s002", "https://dx.doi.org/10.1371/journal.pone.0096057.s003"], "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Genome_Wide_Association_Study_of_Maternal_and_Inherited_Loci_for_Conotruncal_Heart_Defects_/1018135", "title"=>"Genome-Wide Association Study of Maternal and Inherited Loci for Conotruncal Heart Defects", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-05-06 03:35:30"}

PMC Usage Stats | Further Information

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Relative Metric

{"start_date"=>"2014-01-01T00:00:00Z", "end_date"=>"2014-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Computational biology", "average_usage"=>[341, 529]}, {"subject_area"=>"/Engineering and technology/Industrial engineering", "average_usage"=>[262]}, {"subject_area"=>"/Medicine and health sciences", "average_usage"=>[285]}]}
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