{"doi":"10.1371/journal.pgen.1007104","title":"A case-control collapsing analysis identifies epilepsy genes implicated in trio sequencing studies focused on de novo mutations","abstract":null,"journal":"PLOS Genetics","year":2017,"id":631135,"datarank":0.5495342469194471,"base_score":3.6635616461296463,"endowment":3.6635616461296463,"self_citation_contribution":0.5495342469194471,"citation_network_contribution":0.0,"self_endowment_contribution":0.5495342469194471,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":38,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1635474,"name":"Raghavendra Padmanabhan","orcid":null,"position":1,"is_corresponding":false},{"id":857877,"name":"Brett Copeland","orcid":"0000-0003-2933-6061","position":2,"is_corresponding":false},{"id":1592623,"name":"Joshua Bridgers","orcid":null,"position":3,"is_corresponding":false},{"id":417584,"name":"Zhong Ren","orcid":"0000-0001-7098-3127","position":4,"is_corresponding":false},{"id":299863,"name":"Sitharthan Kamalakaran","orcid":null,"position":5,"is_corresponding":false},{"id":1635475,"name":"Ailbhe O'Driscoll-Collins","orcid":"0000-0002-8447-0944","position":6,"is_corresponding":false},{"id":297269,"name":"Samuel F. Berkovic","orcid":"0000-0003-4580-841X","position":7,"is_corresponding":false},{"id":1635476,"name":"Ingrid E. Scheffer","orcid":null,"position":8,"is_corresponding":false},{"id":5709,"name":"Annapurna Poduri","orcid":"0000-0002-7350-5136","position":9,"is_corresponding":false},{"id":855138,"name":"Davide Mei","orcid":"0000-0001-6790-6251","position":10,"is_corresponding":false},{"id":52251,"name":"Renzo Guerrini","orcid":"0000-0002-7272-7079","position":11,"is_corresponding":false},{"id":297272,"name":"Daniel H. Lowenstein","orcid":"0000-0002-9546-2085","position":12,"is_corresponding":false},{"id":29944,"name":"Andrew S. Allen","orcid":"0000-0002-7232-2143","position":13,"is_corresponding":false},{"id":41846,"name":"Erin L. Heinzen","orcid":"0000-0002-7268-8559","position":14,"is_corresponding":false},{"id":297271,"name":"David B. Goldstein","orcid":"0000-0001-7627-0259","position":15,"is_corresponding":false},{"id":1207389,"name":"Xiaolin Zhu","orcid":"0000-0002-3221-595X","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"A case-control collapsing analysis identifies epilepsy genes implicated in trio sequencing studies focused on de novo mutations","abstract":"Trio exome sequencing has been successful in identifying genes with de novo mutations (DNMs) causing epileptic encephalopathy (EE) and other neurodevelopmental disorders. Here, we evaluate how well a case-control collapsing analysis recovers genes causing dominant forms of EE originally implicated by DNM analysis. We performed a genome-wide search for an enrichment of \"qualifying variants\" in protein-coding genes in 488 unrelated cases compared to 12,151 unrelated controls. These \"qualifying variants\" were selected to be extremely rare variants predicted to functionally impact the protein to enrich for likely pathogenic variants. Despite modest sample size, three known EE genes (KCNT1, SCN2A, and STXBP1) achieved genome-wide significance (p<2.68×10-6). In addition, six of the 10 most significantly associated genes are known EE genes, and the majority of the known EE genes (17 out of 25) originally implicated in trio sequencing are nominally significant (p<0.05), a proportion significantly higher than the expected (Fisher's exact p = 2.33×10-17). Our results indicate that a case-control collapsing analysis can identify several of the EE genes originally implicated in trio sequencing studies, and clearly show that additional genes would be implicated with larger sample sizes. The case-control analysis not only makes discovery easier and more economical in early onset disorders, particularly when large cohorts are available, but also supports the use of this approach to identify genes in diseases that present later in life when parents are not readily available.","is_dataset_classified":null,"base_score":3.6635616461296463,"endowment":3.6635616461296463,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"29186148","pmcid":"PMC5724893","openalex_id":"https://openalex.org/W2768522891","authors":[],"funders":[{"funder_name":"NIA NIH HHS","grant_id":"R01 AG037212","title":null},{"funder_name":"NINDS NIH HHS","grant_id":"U01 NS077274","title":null},{"funder_name":"NINDS NIH HHS","grant_id":"U54 NS078059","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"U19 AI067854","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"UM1 AI100645","title":null},{"funder_name":"NICHD NIH 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HHS","grant_id":"U01 HG007672","title":null},{"funder_name":"NINDS NIH HHS","grant_id":"U01 NS053998","title":null},{"funder_name":"NINDS NIH HHS","grant_id":"U01 NS077276","title":null},{"funder_name":"NICHD NIH HHS","grant_id":"P01 HD080642","title":null},{"funder_name":"NINDS NIH HHS","grant_id":"U01 NS077303","title":null},{"funder_name":"NCATS NIH HHS","grant_id":"UL1 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and Rare Diseases","Genomics and Phylogenetic Studies","Genomic variations and chromosomal abnormalities","Case-Control Studies","DNA Mutational Analysis","Epilepsy","Female","Genes, Dominant","Genome-Wide Association Study","Humans","Male","Munc18 Proteins","Mutation","NAV1.2 Voltage-Gated Sodium Channel","Nerve Tissue Proteins","Potassium Channels","Potassium Channels, Sodium-Activated","Exome Sequencing"],"mesh_terms":["Exome Sequencing","Potassium Channels, Sodium-Activated","DNA Mutational Analysis","Epilepsy","Female","Genes, Dominant","Humans","Male","Mutation","Nerve Tissue Proteins","Potassium Channels","Case-Control Studies","Munc18 Proteins","Genome-Wide Association Study","NAV1.2 Voltage-Gated Sodium Channel"],"keywords":["Biology","Gene","Genetics","Exome sequencing","Genome","Exome","Computational 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