{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T13:42:14Z","timestamp":1792590134163,"version":"4.5.0"},"reference-count":67,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,9,6]],"date-time":"2025-09-06T00:00:00Z","timestamp":1757116800000},"content-version":"vor","delay-in-days":189,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100017540","name":"National Heart Lung and Blood Institute Division of Intramural Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000016","name":"U.S. Department of Health and Human Services","doi-asserted-by":"publisher","award":["R01HL162356"],"award-info":[{"award-number":["R01HL162356"]}],"id":[{"id":"10.13039\/100000016","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000016","name":"U.S. Department of Health and Human Services","doi-asserted-by":"publisher","award":["UM1HL098147"],"award-info":[{"award-number":["UM1HL098147"]}],"id":[{"id":"10.13039\/100000016","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000016","name":"U.S. Department of Health and Human Services","doi-asserted-by":"publisher","award":["UM1HL098162"],"award-info":[{"award-number":["UM1HL098162"]}],"id":[{"id":"10.13039\/100000016","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000016","name":"U.S. Department of Health and Human Services","doi-asserted-by":"publisher","award":["UM1HL128761"],"award-info":[{"award-number":["UM1HL128761"]}],"id":[{"id":"10.13039\/100000016","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000016","name":"U.S. Department of Health and Human Services","doi-asserted-by":"publisher","award":["UM1HL098123"],"award-info":[{"award-number":["UM1HL098123"]}],"id":[{"id":"10.13039\/100000016","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000016","name":"U.S. Department of Health and Human Services","doi-asserted-by":"publisher","award":["U01HL131003"],"award-info":[{"award-number":["U01HL131003"]}],"id":[{"id":"10.13039\/100000016","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000016","name":"U.S. Department of Health and Human Services","doi-asserted-by":"publisher","award":["UM1HL128711"],"award-info":[{"award-number":["UM1HL128711"]}],"id":[{"id":"10.13039\/100000016","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR004419"],"award-info":[{"award-number":["UL1TR004419"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["53074"],"award-info":[{"award-number":["53074"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The American Journal of Human Genetics"],"published-print":{"date-parts":[[2025,3]]},"DOI":"10.1016\/j.ajhg.2025.01.024","type":"journal-article","created":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T10:43:10Z","timestamp":1740048190000},"page":"583-598","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":12,"title":["Deciphering the digenic architecture of congenital heart disease using trio exome sequencing data"],"prefix":"10.1016","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5922-5608","authenticated-orcid":false,"given":"Meltem Ece","family":"Kars","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Stein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter D.","family":"Stenson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David N.","family":"Cooper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy K.","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Gruber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine E.","family":"Seidman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufeng","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Tristani-Firouzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce D.","family":"Gelb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuval","family":"Itan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ajhg.2025.01.024_bib1","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1161\/CIRCRESAHA.112.300853","article-title":"Genetics of congenital heart disease: the glass half empty","volume":"112","author":"Fahed","year":"2013","journal-title":"Circ. Res."},{"key":"10.1016\/j.ajhg.2025.01.024_bib2","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1161\/CIRCRESAHA.116.309140","article-title":"Genetics and genomics of congenital heart disease","volume":"120","author":"Zaidi","year":"2017","journal-title":"Circ. Res."},{"key":"10.1016\/j.ajhg.2025.01.024_bib3","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1097\/HCO.0000000000000274","article-title":"Genetics of congenital heart disease","volume":"31","author":"Edwards","year":"2016","journal-title":"Curr. Opin. Cardiol."},{"key":"10.1016\/j.ajhg.2025.01.024_bib4","doi-asserted-by":"crossref","first-page":"e653","DOI":"10.1161\/CIR.0000000000000606","article-title":"Genetic basis for congenital heart disease: revisited: a scientific statement from the American Heart Association","volume":"138","author":"Pierpont","year":"2018","journal-title":"Circulation"},{"key":"10.1016\/j.ajhg.2025.01.024_bib5","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s13073-019-0709-8","article-title":"De novo variants in exomes of congenital heart disease patients identify risk genes and pathways","volume":"12","author":"Sevim Bayrak","year":"2020","journal-title":"Genome Med."},{"key":"10.1016\/j.ajhg.2025.01.024_bib6","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1038\/ng.3627","article-title":"Distinct genetic architectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing","volume":"48","author":"Sifrim","year":"2016","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ajhg.2025.01.024_bib7","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1038\/ng.3970","article-title":"Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands","volume":"49","author":"Jin","year":"2017","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ajhg.2025.01.024_bib8","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1126\/science.aac9396","article-title":"De novo mutations in congenital heart disease with neurodevelopmental and other congenital anomalies","volume":"350","author":"Homsy","year":"2015","journal-title":"Science"},{"key":"10.1016\/j.ajhg.2025.01.024_bib9","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/s41569-021-00587-4","article-title":"Genomic frontiers in congenital heart disease","volume":"19","author":"Morton","year":"2022","journal-title":"Nat. Rev. Cardiol."},{"key":"10.1016\/j.ajhg.2025.01.024_bib10","doi-asserted-by":"crossref","first-page":"18924","DOI":"10.1073\/pnas.2005634117","article-title":"Polygenic inheritance, GWAS, polygenic risk scores, and the search for functional variants","volume":"117","author":"Crouch","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ajhg.2025.01.024_bib11","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1111\/cge.13150","article-title":"Digenic inheritance and genetic modifiers","volume":"93","author":"Deltas","year":"2018","journal-title":"Clin. Genet."},{"key":"10.1016\/j.ajhg.2025.01.024_bib12","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1136\/jmedgenet-2013-101713","article-title":"Digenic inheritance in medical genetics","volume":"50","author":"Schaffer","year":"2013","journal-title":"J.\u00a0Med. Genet."},{"key":"10.1016\/j.ajhg.2025.01.024_bib13","doi-asserted-by":"crossref","first-page":"19367","DOI":"10.1073\/pnas.1920650117","article-title":"A genome-wide case-only test for the detection of digenic inheritance in human exomes","volume":"117","author":"Kerner","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ajhg.2025.01.024_bib14","first-page":"904","article-title":"A general framework for identifying oligogenic combinations of rare variants in complex disorders","volume":"32","author":"Pounraja","year":"2022","journal-title":"Genome Res."},{"key":"10.1016\/j.ajhg.2025.01.024_bib15","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/ejhg.2015.147","article-title":"Genome-wide gene-gene interaction analysis for next-generation sequencing","volume":"24","author":"Zhao","year":"2016","journal-title":"Eur. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2025.01.024_bib16","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0083057","article-title":"A robust model-free approach for rare variants association studies incorporating gene-gene and gene-environmental interactions","volume":"8","author":"Fan","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.ajhg.2025.01.024_bib17","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1038\/s41431-022-01191-x","article-title":"Assessing the digenic model in rare disorders using population sequencing data","volume":"30","author":"Moreno-Ruiz","year":"2022","journal-title":"Eur. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2025.01.024_bib18","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s12918-018-0543-4","article-title":"GxGrare: gene-gene interaction analysis method for rare variants from high-throughput sequencing data","volume":"12","author":"Kwon","year":"2018","journal-title":"BMC Syst. Biol."},{"key":"10.1016\/j.ajhg.2025.01.024_bib19","doi-asserted-by":"crossref","DOI":"10.1161\/CIRCGEN.121.003523","article-title":"CELSR1 risk alleles in familial bicuspid aortic valve and hypoplastic left heart syndrome","volume":"15","author":"Theis","year":"2022","journal-title":"Circ. Genom. Precis. Med."},{"key":"10.1016\/j.ajhg.2025.01.024_bib20","doi-asserted-by":"crossref","DOI":"10.3389\/fcvm.2023.1135141","article-title":"A genetic and developmental biological approach for a family with complex congenital heart diseases-evidence of digenic inheritance","volume":"10","author":"Yoshida","year":"2023","journal-title":"Front. Cardiovasc. Med."},{"key":"10.1016\/j.ajhg.2025.01.024_bib21","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1186\/s12967-023-03994-y","article-title":"Expanding the phenome and variome of the ROBO-SLIT pathway in congenital heart defects: toward improving the genetic testing yield of CHD","volume":"21","author":"Jaouadi","year":"2023","journal-title":"J.\u00a0Transl. Med."},{"key":"10.1016\/j.ajhg.2025.01.024_bib22","article-title":"Assessing the contribution of rare variants to congenital heart disease through a large-scale case-control exome study","author":"Audain","year":"2023","journal-title":"medRxiv"},{"key":"10.1016\/j.ajhg.2025.01.024_bib23","article-title":"An oligogenic inheritance test detects risk genes and their interactions in congenital heart defects and developmental comorbidities","author":"Pittman","year":"2022","journal-title":"bioRxiv"},{"key":"10.1016\/j.ajhg.2025.01.024_bib24","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1161\/CIRCRESAHA.111.300297","article-title":"The Congenital Heart Disease Genetic Network Study: rationale, design, and early results","volume":"112","author":"Gelb","year":"2013","journal-title":"Circ. Res."},{"key":"10.1016\/j.ajhg.2025.01.024_bib25","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.neuron.2010.10.006","article-title":"The Simons Simplex Collection: a resource for identification of autism genetic risk factors","volume":"68","author":"Fischbach","year":"2010","journal-title":"Neuron"},{"key":"10.1016\/j.ajhg.2025.01.024_bib26","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with Burrows-Wheeler transform","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"10.1016\/j.ajhg.2025.01.024_bib27","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1101\/gr.107524.110","article-title":"The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data","volume":"20","author":"McKenna","year":"2010","journal-title":"Genome Res."},{"key":"10.1016\/j.ajhg.2025.01.024_bib28","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/s41586-021-03205-y","article-title":"Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program","volume":"590","author":"Taliun","year":"2021","journal-title":"Nature"},{"key":"10.1016\/j.ajhg.2025.01.024_bib29","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/s41586-020-2308-7","article-title":"The mutational constraint spectrum quantified from variation in 141,456 humans","volume":"581","author":"Karczewski","year":"2020","journal-title":"Nature"},{"key":"10.1016\/j.ajhg.2025.01.024_bib30","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/nature15393","article-title":"A global reference for human genetic variation","volume":"526","author":"Auton","year":"2015","journal-title":"Nature"},{"key":"10.1016\/j.ajhg.2025.01.024_bib31","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s13059-016-0974-4","article-title":"The Ensembl Variant Effect Predictor","volume":"17","author":"McLaren","year":"2016","journal-title":"Genome Biol."},{"key":"10.1016\/j.ajhg.2025.01.024_bib32","doi-asserted-by":"crossref","first-page":"D886","DOI":"10.1093\/nar\/gky1016","article-title":"CADD: predicting the deleteriousness of variants throughout the human genome","volume":"47","author":"Rentzsch","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ajhg.2025.01.024_bib33","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1038\/nmeth.3739","article-title":"The mutation significance cutoff: gene-level thresholds for variant predictions","volume":"13","author":"Itan","year":"2016","journal-title":"Nat. Methods"},{"key":"10.1016\/j.ajhg.2025.01.024_bib34","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41586-023-06045-0","article-title":"A genomic mutational constraint map using variation in 76,156 human genomes","volume":"625","author":"Chen","year":"2024","journal-title":"Nature"},{"key":"10.1016\/j.ajhg.2025.01.024_bib35","doi-asserted-by":"crossref","first-page":"13615","DOI":"10.1073\/pnas.1518646112","article-title":"The human gene damage index as a gene-level approach to prioritizing exome variants","volume":"112","author":"Itan","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ajhg.2025.01.024_bib36","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s13059-016-0869-4","article-title":"The intolerance to functional genetic variation of protein domains predicts the localization of pathogenic mutations within genes","volume":"17","author":"Gussow","year":"2016","journal-title":"Genome Biol."},{"key":"10.1016\/j.ajhg.2025.01.024_bib37","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.1002\/sim.1047","article-title":"A solution to the problem of separation in logistic regression","volume":"21","author":"Heinze","year":"2002","journal-title":"Stat. Med."},{"key":"10.1016\/j.ajhg.2025.01.024_bib38","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.jspi.2003.07.019","article-title":"Choice of a null distribution in resampling-based multiple testing","volume":"125","author":"Pollard","year":"2004","journal-title":"J.\u00a0Stat. Plan. Inference"},{"key":"10.1016\/j.ajhg.2025.01.024_bib39","series-title":"Applied Statistical Genetics with R: For\u00a0Population-Based Association Studies","author":"Foulkes","year":"2009"},{"key":"10.1016\/j.ajhg.2025.01.024_bib40","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1086\/514346","article-title":"Mendelian Inheritance in Man and its online version, OMIM","volume":"80","author":"McKusick","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2025.01.024_bib41","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1007\/s00439-020-02199-3","article-title":"The Human Gene Mutation Database (HGMD\u00ae): optimizing its use in a clinical diagnostic or research setting","volume":"139","author":"Stenson","year":"2020","journal-title":"Hum. Genet."},{"key":"10.1016\/j.ajhg.2025.01.024_bib42","doi-asserted-by":"crossref","first-page":"D1062","DOI":"10.1093\/nar\/gkx1153","article-title":"ClinVar: improving access to variant interpretations and supporting evidence","volume":"46","author":"Landrum","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ajhg.2025.01.024_bib43","doi-asserted-by":"crossref","first-page":"5558","DOI":"10.1073\/pnas.1218167110","article-title":"The human gene connectome as a map of short cuts for morbid allele discovery","volume":"110","author":"Itan","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ajhg.2025.01.024_bib44","doi-asserted-by":"crossref","first-page":"W305","DOI":"10.1093\/nar\/gkp427","article-title":"ToppGene Suite for gene list enrichment analysis and candidate gene prioritization","volume":"37","author":"Chen","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ajhg.2025.01.024_bib45","doi-asserted-by":"crossref","first-page":"W168","DOI":"10.1093\/nar\/gkad393","article-title":"Enrichr-KG: bridging enrichment analysis across multiple libraries","volume":"51","author":"Evangelista","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ajhg.2025.01.024_bib46","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: tool for the unification of biology. The Gene Ontology Consortium","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ajhg.2025.01.024_bib47","doi-asserted-by":"crossref","first-page":"D1333","DOI":"10.1093\/nar\/gkad1005","article-title":"The Human Phenotype Ontology in 2024: phenotypes around the world","volume":"52","author":"Gargano","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ajhg.2025.01.024_bib48","doi-asserted-by":"crossref","first-page":"D981","DOI":"10.1093\/nar\/gkaa1083","article-title":"Mouse Genome Database (MGD): Knowledgebase for mouse-human comparative biology","volume":"49","author":"Blake","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ajhg.2025.01.024_bib49","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1038\/s41586-019-1338-5","article-title":"Gene expression across mammalian organ development","volume":"571","author":"Cardoso-Moreira","year":"2019","journal-title":"Nature"},{"key":"10.1016\/j.ajhg.2025.01.024_bib50","doi-asserted-by":"crossref","first-page":"e34","DOI":"10.1161\/CIRCRESAHA.117.312015","article-title":"Asb2alpha-filamin A axis Is essential for actin cytoskeleton remodeling during heart development","volume":"122","author":"Metais","year":"2018","journal-title":"Circ. Res."},{"key":"10.1016\/j.ajhg.2025.01.024_bib51","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1161\/01.RES.87.5.346","article-title":"Role of gap junctions in cardiac conduction and development: insights from the connexin knockout mice","volume":"87","author":"Lo","year":"2000","journal-title":"Circ. Res."},{"key":"10.1016\/j.ajhg.2025.01.024_bib52","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1002\/ajmg.1265","article-title":"Congenital heart defects in Kabuki syndrome","volume":"100","author":"Digilio","year":"2001","journal-title":"Am. J. Med. Genet."},{"key":"10.1016\/j.ajhg.2025.01.024_bib53","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1111\/cen.13841","article-title":"Comprehensive screening shows that mutations in the known syndromic genes are rare in infants presenting with hyperinsulinaemic hypoglycaemia","volume":"89","author":"Laver","year":"2018","journal-title":"Clin. Endocrinol."},{"key":"10.1016\/j.ajhg.2025.01.024_bib54","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1161\/CIRCGENETICS.115.001070","article-title":"Recessive MYH6 mutations in hypoplastic left heart with reduced ejection fraction","volume":"8","author":"Theis","year":"2015","journal-title":"Circ. Cardiovasc. Genet."},{"key":"10.1016\/j.ajhg.2025.01.024_bib55","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.ajhg.2012.08.017","article-title":"An excess of deleterious variants in VEGF-A pathway genes in Down-syndrome-associated atrioventricular septal defects","volume":"91","author":"Ackerman","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2025.01.024_bib56","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1136\/jmedgenet-2012-101282","article-title":"Asphyxiating thoracic dysplasia: clinical and molecular review of 39 families","volume":"50","author":"Baujat","year":"2013","journal-title":"J.\u00a0Med. Genet."},{"key":"10.1016\/j.ajhg.2025.01.024_bib57","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1002\/ana.24303","article-title":"A comprehensive genomic approach for neuromuscular diseases gives a high diagnostic yield","volume":"77","author":"Ankala","year":"2015","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.ajhg.2025.01.024_bib58","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1111\/ahg.12123","article-title":"Identification of two homozygous sequence variants in the COL7A1 gene underlying dystrophic epidermolysis bullosa by whole-exome analysis in a consanguineous family","volume":"79","author":"Serafi","year":"2015","journal-title":"Ann. Hum. Genet."},{"key":"10.1016\/j.ajhg.2025.01.024_bib59","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1158\/0008-5472.CAN-07-5733","article-title":"Multiple rare nonsynonymous variants in the adenomatous polyposis coli gene predispose to colorectal adenomas","volume":"68","author":"Azzopardi","year":"2008","journal-title":"Cancer Res."},{"key":"10.1016\/j.ajhg.2025.01.024_bib60","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/s41586-018-0579-z","article-title":"The UK Biobank resource with deep phenotyping and genomic data","volume":"562","author":"Bycroft","year":"2018","journal-title":"Nature"},{"key":"10.1016\/j.ajhg.2025.01.024_bib61","doi-asserted-by":"crossref","first-page":"D900","DOI":"10.1093\/nar\/gkv1068","article-title":"DIDA: A curated and annotated digenic diseases database","volume":"44","author":"Gazzo","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ajhg.2025.01.024_bib62","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkx557","article-title":"Understanding mutational effects in digenic diseases","volume":"45","author":"Gazzo","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ajhg.2025.01.024_bib63","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1038\/nature04370","article-title":"Dissection of epistasis in oligogenic Bardet-Biedl syndrome","volume":"439","author":"Badano","year":"2006","journal-title":"Nature"},{"key":"10.1016\/j.ajhg.2025.01.024_bib64","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.ajhg.2010.12.004","article-title":"NEK1 mutations cause short-rib polydactyly syndrome type majewski","volume":"88","author":"Thiel","year":"2011","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2025.01.024_bib65","doi-asserted-by":"crossref","first-page":"263","DOI":"10.3389\/fncel.2016.00263","article-title":"A subset of autism-associated genes regulate the structural stability of neurons","volume":"10","author":"Lin","year":"2016","journal-title":"Front. Cell. Neurosci."},{"key":"10.1016\/j.ajhg.2025.01.024_bib66","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/jhg.2015.141","article-title":"Whole-exome sequencing and neurite outgrowth analysis in autism spectrum disorder","volume":"61","author":"Hashimoto","year":"2016","journal-title":"J.\u00a0Hum. Genet."},{"key":"10.1016\/j.ajhg.2025.01.024_bib67","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1007\/s00018-012-1131-1","article-title":"Heavy and light roles: myosin in the morphogenesis of the heart","volume":"70","author":"England","year":"2013","journal-title":"Cell. Mol. Life Sci."}],"container-title":["The American Journal of Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002929725000448?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002929725000448?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T01:30:52Z","timestamp":1778635852000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0002929725000448"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3]]},"references-count":67,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["S0002929725000448"],"URL":"https:\/\/doi.org\/10.1016\/j.ajhg.2025.01.024","relation":{},"ISSN":["0002-9297"],"issn-type":[{"value":"0002-9297","type":"print"}],"subject":[],"published":{"date-parts":[[2025,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Deciphering the digenic architecture of congenital heart disease using trio exome sequencing data","name":"articletitle","label":"Article Title"},{"value":"The American Journal of Human Genetics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ajhg.2025.01.024","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 American Society of Human Genetics. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}