{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Moreno-Ruiz N"],"funding":["Cancer Research UK","Medical Research Council","National Institute for Health Research (NIHR)","Wellcome Trust"],"pagination":["1439-1443"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9712436"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["30(12)"],"pubmed_abstract":["An important fraction of patients with rare disorders remains with no clear genetic diagnostic, even after whole-exome or whole-genome sequencing, posing a difficulty in giving adequate treatment and genetic counseling. The analysis of genomic data in rare disorders mostly considers the presence of single gene variants in coding regions that follow a concrete monogenic mode of inheritance. A digenic inheritance, with variants in two functionally-related genes in the same individual, is a plausible alternative that might explain the genetic basis of the disease in some cases. In this case, digenic disease combinations should be absent or underrepresented in healthy individuals. We develop a framework to evaluate the significance of digenic combinations and test its statistical power in diff"],"journal":["European journal of human genetics : EJHG"],"pubmed_title":["Assessing the digenic model in rare disorders using population sequencing data."],"pmcid":["PMC9712436"],"funding_grant_id":["MR/M009203/1","MC_EX_MR/M009203/1","MC_PC_14089","NF-SI-0512-10113","NF-SI-0617-10154"],"pubmed_authors":["Stevens HE","Savage K","Craig CEH","Fowler T","Chan GC","Williams E","Sultana R","Smith KR","Boissiere JM","Daugherty LC","Tregidgo C","Pullinger J","Lopez FJ","Walsh E","Maleady-Crowe F","Genomics England Research Consortium","Lahnstein L","Hubbard TJP","Arostegui JI","Watters SA","Welland MJ","Stuckey A","Elgar G","Holman JE","Sieghart A","Zarowiecki M","Caulfield MJ","Hamblin A","Mueller M","Orioli A","Laayouni H","Ambrose JC","Scott RH","Spooner W","McDonagh EM","Tucci A","Moutsianas L","Bleda M","Leigh SEA","Patch C","Thomas ERA","Brittain H","Jones LJ","Mason J","Arumugam P","Kasperaviciute D","Ryten M","Hackett JM","Riesgo-Ferreiro P","Henderson S","Casals F","Pereira MB","Rogers T","Boardman-Pretty F","Polychronopoulos D","Baple EL","Lawson K","Kayikci M","Halai D","Thompson SR","Ibanez K","Murugaesu N","Leong IUS","Kousathanas A","Smedley D","Witkowska K","Tanguy M","Furio-Tari P","Smith SC","Jackson R","Giess A","Rendon A","Moreno-Ruiz N","Sosinsky A","Foulger RE","Perez-Gil D","Need AC","Sawant K","Boustred CR","de Burca A","Lao O","Siddiq A","Odhams CA","Rahim T","Devereau A","Wood SM"],"additional_accession":[]},"is_claimable":false,"name":"Assessing the digenic model in rare disorders using population sequencing data.","description":"An important fraction of patients with rare disorders remains with no clear genetic diagnostic, even after whole-exome or whole-genome sequencing, posing a difficulty in giving adequate treatment and genetic counseling. The analysis of genomic data in rare disorders mostly considers the presence of single gene variants in coding regions that follow a concrete monogenic mode of inheritance. A digenic inheritance, with variants in two functionally-related genes in the same individual, is a plausible alternative that might explain the genetic basis of the disease in some cases. In this case, digenic disease combinations should be absent or underrepresented in healthy individuals. We develop a framework to evaluate the significance of digenic combinations and test its statistical power in diff","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Dec","modification":"2025-04-18T16:56:12.578Z","creation":"2025-04-07T04:24:34.916Z"},"accession":"S-EPMC9712436","cross_references":{"pubmed":["36192439"],"doi":["10.1038/s41431-022-01191-x"]}}