Identification of Medically Actionable Secondary Findings in the 1000 Genomes
Publication Date
September 02, 2015
Journal
PLOS ONE
Authors
Emily Olfson, Catherine E. Cottrell, Nicholas O. Davidson, Christina A. Gurnett, et al
Volume
10
Issue
9
Pages
e0135193
DOI
https://dx.plos.org/10.1371/journal.pone.0135193
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0135193
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/26332594
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4558085
Europe PMC
http://europepmc.org/abstract/MED/26332594
Web of Science
000360613800022
Scopus
84947461294
Mendeley
http://www.mendeley.com/research/identification-medically-actionable-secondary-findings-1000-genomes
Events
Loading … Spinner

Mendeley | Further Information

{"title"=>"Identification of medically actionable secondary findings in the 1000 genomes", "type"=>"journal", "authors"=>[{"first_name"=>"Emily", "last_name"=>"Olfson", "scopus_author_id"=>"16639095000"}, {"first_name"=>"Catherine E.", "last_name"=>"Cottrell", "scopus_author_id"=>"36120062100"}, {"first_name"=>"Nicholas O.", "last_name"=>"Davidson", "scopus_author_id"=>"7202245995"}, {"first_name"=>"Christina A.", "last_name"=>"Gurnett", "scopus_author_id"=>"6701464580"}, {"first_name"=>"Jonathan W.", "last_name"=>"Heusel", "scopus_author_id"=>"6602344937"}, {"first_name"=>"Nathan O.", "last_name"=>"Stitziel", "scopus_author_id"=>"6507357414"}, {"first_name"=>"Li Shiun", "last_name"=>"Chen", "scopus_author_id"=>"7409440955"}, {"first_name"=>"Sarah", "last_name"=>"Hartz", "scopus_author_id"=>"35329642500"}, {"first_name"=>"Rakesh", "last_name"=>"Nagarajan", "scopus_author_id"=>"7202927147"}, {"first_name"=>"Nancy L.", "last_name"=>"Saccone", "scopus_author_id"=>"6603709921"}, {"first_name"=>"Laura J.", "last_name"=>"Bierut", "scopus_author_id"=>"6701374894"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"26332594", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0135193", "pui"=>"606945992", "isbn"=>"1932-6203 (Electronic)\r1932-6203 (Linking)", "scopus"=>"2-s2.0-84947461294", "sgr"=>"84947461294"}, "id"=>"58a8e2e2-586a-31bb-96da-6bf6826cc857", "abstract"=>"The American College of Medical Genetics and Genomics (ACMG) recommends that clinical sequencing laboratories return secondary findings in 56 genes associated with medically actionable conditions. Our goal was to apply a systematic, stringent approach consistent with clinical standards to estimate the prevalence of pathogenic variants associated with such conditions using a diverse sequencing reference sample. Candidate variants in the 56 ACMG genes were selected from Phase 1 of the 1000 Genomes dataset, which contains sequencing information on 1,092 unrelated individuals from across the world. These variants were filtered using the Human Gene Mutation Database (HGMD) Professional version and defined parameters, appraised through literature review, and examined by a clinical laboratory specialist and expert physician. Over 70,000 genetic variants were extracted from the 56 genes, and filtering identified 237 variants annotated as disease causing by HGMD Professional. Literature review and expert evaluation determined that 7 of these variants were pathogenic or likely pathogenic. Furthermore, 5 additional truncating variants not listed as disease causing in HGMD Professional were identified as likely pathogenic. These 12 secondary findings are associated with diseases that could inform medical follow-up, including cancer predisposition syndromes, cardiac conditions, and familial hypercholesterolemia. The majority of the identified medically actionable findings were in individuals from the European (5/379) and Americas (4/181) ancestry groups, with fewer findings in Asian (2/286) and African (1/246) ancestry groups. Our results suggest that medically relevant secondary findings can be identified in approximately 1% (12/1092) of individuals in a diverse reference sample. As clinical sequencing laboratories continue to implement the ACMG recommendations, our results highlight that at least a small number of potentially important secondary findings can be selected for return. Our results also confirm that understudied populations will not reap proportionate benefits of genomic medicine, highlighting the need for continued research efforts on genetic diseases in these populations.", "link"=>"http://www.mendeley.com/research/identification-medically-actionable-secondary-findings-1000-genomes", "reader_count"=>42, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Librarian"=>1, "Researcher"=>15, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>1, "Other"=>3, "Student > Master"=>3, "Student > Bachelor"=>5, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Librarian"=>1, "Researcher"=>15, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>1, "Other"=>3, "Student > Master"=>3, "Student > Bachelor"=>5, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>15, "Mathematics"=>1, "Agricultural and Biological Sciences"=>12, "Medicine and Dentistry"=>8, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Psychology"=>1, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>8}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>12}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>15}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>3}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"United States"=>1, "Spain"=>1}, "group_count"=>3}

CrossRef

Scopus | Further Information

{"@_fa"=>"true", "link"=>[{"@_fa"=>"true", "@ref"=>"self", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84947461294"}, {"@_fa"=>"true", "@ref"=>"author-affiliation", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84947461294?field=author,affiliation"}, {"@_fa"=>"true", "@ref"=>"scopus", "@href"=>"https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84947461294&origin=inward"}, {"@_fa"=>"true", "@ref"=>"scopus-citedby", "@href"=>"https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=84947461294&origin=inward"}], "prism:url"=>"https://api.elsevier.com/content/abstract/scopus_id/84947461294", "dc:identifier"=>"SCOPUS_ID:84947461294", "eid"=>"2-s2.0-84947461294", "dc:title"=>"Identification of medically actionable secondary findings in the 1000 genomes", "dc:creator"=>"Olfson E.", "prism:publicationName"=>"PLoS ONE", "prism:eIssn"=>"19326203", "prism:volume"=>"10", "prism:issueIdentifier"=>"9", "prism:pageRange"=>nil, "prism:coverDate"=>"2015-09-02", "prism:coverDisplayDate"=>"2 September 2015", "prism:doi"=>"10.1371/journal.pone.0135193", "citedby-count"=>"42", "affiliation"=>[{"@_fa"=>"true", "affilname"=>"Washington University School of Medicine in St. Louis", "affiliation-city"=>"St. Louis", "affiliation-country"=>"United States"}], "pubmed-id"=>"26332594", "prism:aggregationType"=>"Journal", "subtype"=>"ar", "subtypeDescription"=>"Article", "article-number"=>"e0135193", "source-id"=>"10600153309", "openaccess"=>"1", "openaccessFlag"=>true}

Facebook

  • {"url"=>"http%3A%2F%2Fjournals.plos.org%2Fplosone%2Farticle%3Fid%3D10.1371%252Fjournal.pone.0135193", "share_count"=>2, "like_count"=>0, "comment_count"=>0, "click_count"=>0, "total_count"=>2}

Twitter

Counter

  • {"month"=>"9", "year"=>"2015", "pdf_views"=>"107", "xml_views"=>"5", "html_views"=>"695"}
  • {"month"=>"10", "year"=>"2015", "pdf_views"=>"27", "xml_views"=>"0", "html_views"=>"93"}
  • {"month"=>"11", "year"=>"2015", "pdf_views"=>"19", "xml_views"=>"1", "html_views"=>"57"}
  • {"month"=>"12", "year"=>"2015", "pdf_views"=>"18", "xml_views"=>"0", "html_views"=>"89"}
  • {"month"=>"1", "year"=>"2016", "pdf_views"=>"33", "xml_views"=>"0", "html_views"=>"128"}
  • {"month"=>"2", "year"=>"2016", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"101"}
  • {"month"=>"3", "year"=>"2016", "pdf_views"=>"39", "xml_views"=>"0", "html_views"=>"97"}
  • {"month"=>"4", "year"=>"2016", "pdf_views"=>"18", "xml_views"=>"0", "html_views"=>"85"}
  • {"month"=>"5", "year"=>"2016", "pdf_views"=>"21", "xml_views"=>"0", "html_views"=>"61"}
  • {"month"=>"6", "year"=>"2016", "pdf_views"=>"31", "xml_views"=>"0", "html_views"=>"74"}
  • {"month"=>"7", "year"=>"2016", "pdf_views"=>"20", "xml_views"=>"0", "html_views"=>"70"}
  • {"month"=>"8", "year"=>"2016", "pdf_views"=>"26", "xml_views"=>"0", "html_views"=>"66"}
  • {"month"=>"9", "year"=>"2016", "pdf_views"=>"31", "xml_views"=>"0", "html_views"=>"89"}
  • {"month"=>"10", "year"=>"2016", "pdf_views"=>"26", "xml_views"=>"0", "html_views"=>"71"}
  • {"month"=>"11", "year"=>"2016", "pdf_views"=>"17", "xml_views"=>"0", "html_views"=>"82"}
  • {"month"=>"12", "year"=>"2016", "pdf_views"=>"33", "xml_views"=>"0", "html_views"=>"72"}
  • {"month"=>"1", "year"=>"2017", "pdf_views"=>"28", "xml_views"=>"0", "html_views"=>"75"}
  • {"month"=>"2", "year"=>"2017", "pdf_views"=>"25", "xml_views"=>"1", "html_views"=>"66"}
  • {"month"=>"3", "year"=>"2017", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"65"}
  • {"month"=>"4", "year"=>"2017", "pdf_views"=>"19", "xml_views"=>"3", "html_views"=>"75"}
  • {"month"=>"5", "year"=>"2017", "pdf_views"=>"24", "xml_views"=>"2", "html_views"=>"148"}
  • {"month"=>"6", "year"=>"2017", "pdf_views"=>"25", "xml_views"=>"2", "html_views"=>"130"}
  • {"month"=>"7", "year"=>"2017", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"73"}
  • {"month"=>"8", "year"=>"2017", "pdf_views"=>"29", "xml_views"=>"1", "html_views"=>"74"}
  • {"month"=>"9", "year"=>"2017", "pdf_views"=>"19", "xml_views"=>"1", "html_views"=>"78"}
  • {"month"=>"10", "year"=>"2017", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"53"}
  • {"month"=>"11", "year"=>"2017", "pdf_views"=>"17", "xml_views"=>"0", "html_views"=>"110"}
  • {"month"=>"12", "year"=>"2017", "pdf_views"=>"23", "xml_views"=>"1", "html_views"=>"139"}
  • {"month"=>"1", "year"=>"2018", "pdf_views"=>"20", "xml_views"=>"0", "html_views"=>"61"}
  • {"month"=>"2", "year"=>"2018", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"43"}
  • {"month"=>"3", "year"=>"2018", "pdf_views"=>"18", "xml_views"=>"2", "html_views"=>"41"}
  • {"month"=>"4", "year"=>"2018", "pdf_views"=>"21", "xml_views"=>"0", "html_views"=>"24"}
  • {"month"=>"5", "year"=>"2018", "pdf_views"=>"49", "xml_views"=>"6", "html_views"=>"49"}
  • {"month"=>"6", "year"=>"2018", "pdf_views"=>"23", "xml_views"=>"4", "html_views"=>"41"}
  • {"month"=>"7", "year"=>"2018", "pdf_views"=>"15", "xml_views"=>"7", "html_views"=>"22"}
  • {"month"=>"8", "year"=>"2018", "pdf_views"=>"11", "xml_views"=>"2", "html_views"=>"31"}
  • {"month"=>"9", "year"=>"2018", "pdf_views"=>"23", "xml_views"=>"0", "html_views"=>"39"}
  • {"month"=>"10", "year"=>"2018", "pdf_views"=>"13", "xml_views"=>"1", "html_views"=>"38"}
  • {"month"=>"11", "year"=>"2018", "pdf_views"=>"27", "xml_views"=>"0", "html_views"=>"52"}
  • {"month"=>"12", "year"=>"2018", "pdf_views"=>"17", "xml_views"=>"1", "html_views"=>"32"}
  • {"month"=>"1", "year"=>"2019", "pdf_views"=>"43", "xml_views"=>"0", "html_views"=>"37"}
  • {"month"=>"2", "year"=>"2019", "pdf_views"=>"14", "xml_views"=>"1", "html_views"=>"31"}
  • {"month"=>"3", "year"=>"2019", "pdf_views"=>"23", "xml_views"=>"1", "html_views"=>"45"}
  • {"month"=>"4", "year"=>"2019", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"36"}
  • {"month"=>"5", "year"=>"2019", "pdf_views"=>"35", "xml_views"=>"0", "html_views"=>"37"}
  • {"month"=>"6", "year"=>"2019", "pdf_views"=>"28", "xml_views"=>"2", "html_views"=>"47"}
  • {"month"=>"7", "year"=>"2019", "pdf_views"=>"17", "xml_views"=>"0", "html_views"=>"42"}
  • {"month"=>"8", "year"=>"2019", "pdf_views"=>"21", "xml_views"=>"0", "html_views"=>"46"}
  • {"month"=>"9", "year"=>"2019", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"41"}
  • {"month"=>"10", "year"=>"2019", "pdf_views"=>"18", "xml_views"=>"0", "html_views"=>"46"}
  • {"month"=>"11", "year"=>"2019", "pdf_views"=>"20", "xml_views"=>"0", "html_views"=>"44"}
  • {"month"=>"12", "year"=>"2019", "pdf_views"=>"17", "xml_views"=>"0", "html_views"=>"28"}
  • {"month"=>"1", "year"=>"2020", "pdf_views"=>"19", "xml_views"=>"0", "html_views"=>"35"}
  • {"month"=>"2", "year"=>"2020", "pdf_views"=>"22", "xml_views"=>"1", "html_views"=>"47"}
  • {"month"=>"3", "year"=>"2020", "pdf_views"=>"17", "xml_views"=>"1", "html_views"=>"32"}
  • {"month"=>"4", "year"=>"2020", "pdf_views"=>"42", "xml_views"=>"1", "html_views"=>"25"}
  • {"month"=>"5", "year"=>"2020", "pdf_views"=>"29", "xml_views"=>"1", "html_views"=>"22"}
  • {"month"=>"6", "year"=>"2020", "pdf_views"=>"21", "xml_views"=>"2", "html_views"=>"25"}
  • {"month"=>"7", "year"=>"2020", "pdf_views"=>"28", "xml_views"=>"2", "html_views"=>"39"}
  • {"month"=>"8", "year"=>"2020", "pdf_views"=>"29", "xml_views"=>"0", "html_views"=>"61"}
  • {"month"=>"9", "year"=>"2020", "pdf_views"=>"29", "xml_views"=>"0", "html_views"=>"43"}
  • {"month"=>"10", "year"=>"2020", "pdf_views"=>"24", "xml_views"=>"1", "html_views"=>"37"}
  • {"month"=>"11", "year"=>"2020", "pdf_views"=>"29", "xml_views"=>"0", "html_views"=>"22"}

Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2250603"], "description"=>"<p>Candidate variants in 56 genes associated with 24 actionable conditions from the 1000 Genomes dataset were narrowed down to identify 7 secondary findings that specialists agree are pathogenic or likely pathogenic.</p>", "links"=>[], "tags"=>["finding", "sequencing laboratories return", "Human Gene Mutation Database", "56 genes", "individual", "laboratory", "HGMD Professional", "sequencing reference sample", "56 ACMG genes", "literature review", "cancer predisposition syndromes", "1000 Genomes dataset", "variant"], "article_id"=>1533590, "categories"=>["Biological Sciences"], "users"=>["Emily Olfson", "Catherine E. Cottrell", "Nicholas O. Davidson", "Christina A. Gurnett", "Jonathan W. Heusel", "Nathan O. Stitziel", "Li-Shiun Chen", "Sarah Hartz", "Rakesh Nagarajan", "Nancy L. Saccone", "Laura J. Bierut"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0135193.g001", "stats"=>{"downloads"=>4, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Flow_of_candidate_variants_through_informatics_filtering_literature_review_and_expert_evaluation_/1533590", "title"=>"Flow of candidate variants through informatics filtering, literature review, and expert evaluation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-09-02 03:09:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/2250605"], "description"=>"<p>These graphs compare the number of variants per person at different stages of the literature screen across the four major ancestry groups in the 1000 Genomes dataset. A) Compares the contribution of variants that were removed because of a high frequency in reference datasets to all of the other filtered variants. B) Compares the contribution to variants per person of all of the filtered variants that did not have a high frequency in reference datasets. Specifically, it compares the contribution of variants with evidence against a conclusion of pathogenicity, a lack of supportive evidence, literature on a different disorder, or those that were retained for specialist review.</p>", "links"=>[], "tags"=>["finding", "sequencing laboratories return", "Human Gene Mutation Database", "56 genes", "individual", "laboratory", "HGMD Professional", "sequencing reference sample", "56 ACMG genes", "literature review", "cancer predisposition syndromes", "1000 Genomes dataset", "variant"], "article_id"=>1533592, "categories"=>["Biological Sciences"], "users"=>["Emily Olfson", "Catherine E. Cottrell", "Nicholas O. Davidson", "Christina A. Gurnett", "Jonathan W. Heusel", "Nathan O. Stitziel", "Li-Shiun Chen", "Sarah Hartz", "Rakesh Nagarajan", "Nancy L. Saccone", "Laura J. Bierut"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0135193.g002", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Results_of_literature_screen_of_237_filtered_candidate_variants_/1533592", "title"=>"Results of literature screen of 237 filtered candidate variants.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-09-02 03:09:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/2250606"], "description"=>"<p>* Genes for which novel, expected pathogenic variants should be returned.</p><p>Number of candidate variants after different review stages.</p>", "links"=>[], "tags"=>["finding", "sequencing laboratories return", "Human Gene Mutation Database", "56 genes", "individual", "laboratory", "HGMD Professional", "sequencing reference sample", "56 ACMG genes", "literature review", "cancer predisposition syndromes", "1000 Genomes dataset", "variant"], "article_id"=>1533593, "categories"=>["Biological Sciences"], "users"=>["Emily Olfson", "Catherine E. Cottrell", "Nicholas O. Davidson", "Christina A. Gurnett", "Jonathan W. Heusel", "Nathan O. Stitziel", "Li-Shiun Chen", "Sarah Hartz", "Rakesh Nagarajan", "Nancy L. Saccone", "Laura J. Bierut"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0135193.t001", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Number_of_candidate_variants_after_different_review_stages_/1533593", "title"=>"Number of candidate variants after different review stages.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-09-02 03:09:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/2250608"], "description"=>"<p>Distribution of variants per person after filtering, literature screening, and specialist review.</p>", "links"=>[], "tags"=>["finding", "sequencing laboratories return", "Human Gene Mutation Database", "56 genes", "individual", "laboratory", "HGMD Professional", "sequencing reference sample", "56 ACMG genes", "literature review", "cancer predisposition syndromes", "1000 Genomes dataset", "variant"], "article_id"=>1533595, "categories"=>["Biological Sciences"], "users"=>["Emily Olfson", "Catherine E. Cottrell", "Nicholas O. Davidson", "Christina A. Gurnett", "Jonathan W. Heusel", "Nathan O. Stitziel", "Li-Shiun Chen", "Sarah Hartz", "Rakesh Nagarajan", "Nancy L. Saccone", "Laura J. Bierut"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0135193.t002", "stats"=>{"downloads"=>8, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Distribution_of_variants_per_person_after_filtering_literature_screening_and_specialist_review_/1533595", "title"=>"Distribution of variants per person after filtering, literature screening, and specialist review.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-09-02 03:09:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/2250609"], "description"=>"<p><sup><i>a</i></sup>AFR, African.</p><p><sup><i>b</i></sup>EUR, European.</p><p><sup><i>c</i></sup>ASN, East Asian.</p><p><sup><i>d</i></sup>AMR, the Americas.</p><p><sup><i>e</i></sup>Splice variant.</p><p>Pathogenic variants that the clinical laboratory specialist and expert physicians agree should be disclosed as secondary findings.</p>", "links"=>[], "tags"=>["finding", "sequencing laboratories return", "Human Gene Mutation Database", "56 genes", "individual", "laboratory", "HGMD Professional", "sequencing reference sample", "56 ACMG genes", "literature review", "cancer predisposition syndromes", "1000 Genomes dataset", "variant"], "article_id"=>1533596, "categories"=>["Biological Sciences"], "users"=>["Emily Olfson", "Catherine E. Cottrell", "Nicholas O. Davidson", "Christina A. Gurnett", "Jonathan W. Heusel", "Nathan O. Stitziel", "Li-Shiun Chen", "Sarah Hartz", "Rakesh Nagarajan", "Nancy L. Saccone", "Laura J. Bierut"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0135193.t003", "stats"=>{"downloads"=>15, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Pathogenic_variants_that_the_clinical_laboratory_specialist_and_expert_physicians_agree_should_be_disclosed_as_secondary_findings_/1533596", "title"=>"Pathogenic variants that the clinical laboratory specialist and expert physicians agree should be disclosed as secondary findings.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-09-02 03:09:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/2250610"], "description"=>"<p><sup><i>a</i></sup>AMR, the Americas.</p><p><sup><i>b</i></sup>EUR, European.</p><p><sup><i>c</i></sup>ASN, East Asian.</p><p>Additional expected pathogenic variants that meet criteria for disclosure as secondary findings.</p>", "links"=>[], "tags"=>["finding", "sequencing laboratories return", "Human Gene Mutation Database", "56 genes", "individual", "laboratory", "HGMD Professional", "sequencing reference sample", "56 ACMG genes", "literature review", "cancer predisposition syndromes", "1000 Genomes dataset", "variant"], "article_id"=>1533597, "categories"=>["Biological Sciences"], "users"=>["Emily Olfson", "Catherine E. Cottrell", "Nicholas O. Davidson", "Christina A. Gurnett", "Jonathan W. Heusel", "Nathan O. Stitziel", "Li-Shiun Chen", "Sarah Hartz", "Rakesh Nagarajan", "Nancy L. Saccone", "Laura J. Bierut"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0135193.t004", "stats"=>{"downloads"=>0, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Additional_expected_pathogenic_variants_that_meet_criteria_for_disclosure_as_secondary_findings_/1533597", "title"=>"Additional expected pathogenic variants that meet criteria for disclosure as secondary findings.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-09-02 03:09:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/2250612", "https://ndownloader.figshare.com/files/2250613"], "description"=>"<div><p>The American College of Medical Genetics and Genomics (ACMG) recommends that clinical sequencing laboratories return secondary findings in 56 genes associated with medically actionable conditions. Our goal was to apply a systematic, stringent approach consistent with clinical standards to estimate the prevalence of pathogenic variants associated with such conditions using a diverse sequencing reference sample. Candidate variants in the 56 ACMG genes were selected from Phase 1 of the 1000 Genomes dataset, which contains sequencing information on 1,092 unrelated individuals from across the world. These variants were filtered using the Human Gene Mutation Database (HGMD) Professional version and defined parameters, appraised through literature review, and examined by a clinical laboratory specialist and expert physician. Over 70,000 genetic variants were extracted from the 56 genes, and filtering identified 237 variants annotated as disease causing by HGMD Professional. Literature review and expert evaluation determined that 7 of these variants were pathogenic or likely pathogenic. Furthermore, 5 additional truncating variants not listed as disease causing in HGMD Professional were identified as likely pathogenic. These 12 secondary findings are associated with diseases that could inform medical follow-up, including cancer predisposition syndromes, cardiac conditions, and familial hypercholesterolemia. The majority of the identified medically actionable findings were in individuals from the European (5/379) and Americas (4/181) ancestry groups, with fewer findings in Asian (2/286) and African (1/246) ancestry groups. Our results suggest that medically relevant secondary findings can be identified in approximately 1% (12/1092) of individuals in a diverse reference sample. As clinical sequencing laboratories continue to implement the ACMG recommendations, our results highlight that at least a small number of potentially important secondary findings can be selected for return. Our results also confirm that understudied populations will not reap proportionate benefits of genomic medicine, highlighting the need for continued research efforts on genetic diseases in these populations.</p></div>", "links"=>[], "tags"=>["finding", "sequencing laboratories return", "Human Gene Mutation Database", "56 genes", "individual", "laboratory", "HGMD Professional", "sequencing reference sample", "56 ACMG genes", "literature review", "cancer predisposition syndromes", "1000 Genomes dataset", "variant"], "article_id"=>1533599, "categories"=>["Biological Sciences"], "users"=>["Emily Olfson", "Catherine E. Cottrell", "Nicholas O. Davidson", "Christina A. Gurnett", "Jonathan W. Heusel", "Nathan O. Stitziel", "Li-Shiun Chen", "Sarah Hartz", "Rakesh Nagarajan", "Nancy L. Saccone", "Laura J. Bierut"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0135193.s001", "https://dx.doi.org/10.1371/journal.pone.0135193.s002"], "stats"=>{"downloads"=>44, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Identification_of_Medically_Actionable_Secondary_Findings_in_the_1000_Genomes_/1533599", "title"=>"Identification of Medically Actionable Secondary Findings in the 1000 Genomes", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-09-02 03:09:06"}

PMC Usage Stats | Further Information

  • {"unique-ip"=>"36", "full-text"=>"49", "pdf"=>"18", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2015", "month"=>"9"}
  • {"unique-ip"=>"37", "full-text"=>"39", "pdf"=>"16", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"6", "cited-by"=>"0", "year"=>"2015", "month"=>"10"}
  • {"unique-ip"=>"59", "full-text"=>"85", "pdf"=>"36", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"29", "cited-by"=>"0", "year"=>"2016", "month"=>"2"}
  • {"unique-ip"=>"38", "full-text"=>"37", "pdf"=>"22", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"8", "cited-by"=>"0", "year"=>"2015", "month"=>"11"}
  • {"unique-ip"=>"48", "full-text"=>"55", "pdf"=>"26", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"19", "cited-by"=>"0", "year"=>"2015", "month"=>"12"}
  • {"unique-ip"=>"70", "full-text"=>"95", "pdf"=>"50", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"47", "cited-by"=>"0", "year"=>"2016", "month"=>"1"}
  • {"unique-ip"=>"58", "full-text"=>"95", "pdf"=>"50", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"51", "cited-by"=>"0", "year"=>"2016", "month"=>"3"}
  • {"unique-ip"=>"75", "full-text"=>"102", "pdf"=>"56", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"16", "supp-data"=>"45", "cited-by"=>"0", "year"=>"2016", "month"=>"4"}
  • {"unique-ip"=>"56", "full-text"=>"86", "pdf"=>"36", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"31", "cited-by"=>"0", "year"=>"2016", "month"=>"5"}
  • {"unique-ip"=>"64", "full-text"=>"86", "pdf"=>"35", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"37", "cited-by"=>"0", "year"=>"2016", "month"=>"6"}
  • {"unique-ip"=>"66", "full-text"=>"87", "pdf"=>"39", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"38", "cited-by"=>"0", "year"=>"2016", "month"=>"7"}
  • {"unique-ip"=>"51", "full-text"=>"73", "pdf"=>"32", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"30", "cited-by"=>"0", "year"=>"2016", "month"=>"8"}
  • {"unique-ip"=>"66", "full-text"=>"81", "pdf"=>"32", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"42", "cited-by"=>"0", "year"=>"2016", "month"=>"9"}
  • {"unique-ip"=>"54", "full-text"=>"65", "pdf"=>"40", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"27", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
  • {"unique-ip"=>"57", "full-text"=>"78", "pdf"=>"39", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"28", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
  • {"unique-ip"=>"49", "full-text"=>"64", "pdf"=>"21", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"29", "cited-by"=>"6", "year"=>"2016", "month"=>"12"}
  • {"unique-ip"=>"73", "full-text"=>"95", "pdf"=>"39", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"13", "supp-data"=>"53", "cited-by"=>"1", "year"=>"2017", "month"=>"1"}
  • {"unique-ip"=>"52", "full-text"=>"69", "pdf"=>"32", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"30", "cited-by"=>"0", "year"=>"2017", "month"=>"2"}
  • {"unique-ip"=>"53", "full-text"=>"72", "pdf"=>"25", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"13", "supp-data"=>"27", "cited-by"=>"0", "year"=>"2017", "month"=>"3"}
  • {"unique-ip"=>"49", "full-text"=>"56", "pdf"=>"26", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"18", "cited-by"=>"0", "year"=>"2017", "month"=>"4"}
  • {"unique-ip"=>"37", "full-text"=>"51", "pdf"=>"24", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"19", "cited-by"=>"0", "year"=>"2017", "month"=>"5"}
  • {"unique-ip"=>"45", "full-text"=>"62", "pdf"=>"28", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"12", "supp-data"=>"25", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
  • {"unique-ip"=>"38", "full-text"=>"50", "pdf"=>"20", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"25", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
  • {"unique-ip"=>"44", "full-text"=>"62", "pdf"=>"22", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"22", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
  • {"unique-ip"=>"38", "full-text"=>"53", "pdf"=>"12", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"11", "supp-data"=>"17", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
  • {"unique-ip"=>"47", "full-text"=>"57", "pdf"=>"18", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"25", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}
  • {"unique-ip"=>"53", "full-text"=>"63", "pdf"=>"21", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"38", "cited-by"=>"0", "year"=>"2017", "month"=>"11"}
  • {"unique-ip"=>"37", "full-text"=>"47", "pdf"=>"20", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"20", "cited-by"=>"0", "year"=>"2017", "month"=>"12"}
  • {"unique-ip"=>"52", "full-text"=>"57", "pdf"=>"25", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"22", "cited-by"=>"0", "year"=>"2018", "month"=>"1"}
  • {"unique-ip"=>"3", "full-text"=>"4", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2018", "month"=>"2"}
  • {"unique-ip"=>"54", "full-text"=>"67", "pdf"=>"31", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"33", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
  • {"unique-ip"=>"67", "full-text"=>"76", "pdf"=>"18", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"40", "cited-by"=>"0", "year"=>"2019", "month"=>"1"}
  • {"unique-ip"=>"62", "full-text"=>"81", "pdf"=>"23", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"27", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"62", "full-text"=>"84", "pdf"=>"37", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"25", "cited-by"=>"0", "year"=>"2018", "month"=>"4"}
  • {"unique-ip"=>"64", "full-text"=>"90", "pdf"=>"26", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"20", "cited-by"=>"0", "year"=>"2018", "month"=>"5"}
  • {"unique-ip"=>"76", "full-text"=>"96", "pdf"=>"29", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"34", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"57", "full-text"=>"85", "pdf"=>"29", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"34", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"54", "full-text"=>"77", "pdf"=>"25", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"27", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"56", "full-text"=>"74", "pdf"=>"20", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"48", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"68", "full-text"=>"79", "pdf"=>"28", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"27", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"78", "full-text"=>"103", "pdf"=>"26", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"26", "cited-by"=>"2", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"54", "full-text"=>"72", "pdf"=>"17", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"30", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"75", "full-text"=>"104", "pdf"=>"27", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"36", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"65", "full-text"=>"81", "pdf"=>"28", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"45", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"75", "full-text"=>"178", "pdf"=>"38", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"25", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"50", "full-text"=>"200", "pdf"=>"15", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"27", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"62", "full-text"=>"77", "pdf"=>"27", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"37", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
  • {"unique-ip"=>"62", "full-text"=>"77", "pdf"=>"16", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"31", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}
  • {"unique-ip"=>"36", "full-text"=>"48", "pdf"=>"11", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"14", "cited-by"=>"0", "year"=>"2019", "month"=>"12"}
  • {"unique-ip"=>"52", "full-text"=>"85", "pdf"=>"16", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"25", "cited-by"=>"0", "year"=>"2020", "month"=>"2"}
  • {"unique-ip"=>"52", "full-text"=>"63", "pdf"=>"8", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"27", "cited-by"=>"0", "year"=>"2020", "month"=>"3"}
  • {"unique-ip"=>"53", "full-text"=>"65", "pdf"=>"14", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"25", "cited-by"=>"0", "year"=>"2020", "month"=>"4"}
  • {"unique-ip"=>"37", "full-text"=>"49", "pdf"=>"13", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"17", "cited-by"=>"0", "year"=>"2020", "month"=>"5"}
  • {"unique-ip"=>"44", "full-text"=>"55", "pdf"=>"15", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"24", "cited-by"=>"0", "year"=>"2020", "month"=>"6"}
  • {"unique-ip"=>"40", "full-text"=>"48", "pdf"=>"18", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"21", "cited-by"=>"0", "year"=>"2020", "month"=>"7"}
  • {"unique-ip"=>"38", "full-text"=>"40", "pdf"=>"7", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"25", "cited-by"=>"0", "year"=>"2020", "month"=>"8"}
  • {"unique-ip"=>"38", "full-text"=>"42", "pdf"=>"11", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"19", "cited-by"=>"1", "year"=>"2020", "month"=>"9"}
  • {"unique-ip"=>"39", "full-text"=>"55", "pdf"=>"10", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"27", "cited-by"=>"0", "year"=>"2020", "month"=>"10"}

Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
Loading … Spinner
There are currently no alerts