{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T18:16:06Z","timestamp":1792692966817,"version":"4.5.0"},"reference-count":67,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Genomic and Precision Medicine"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Deciphering hypoplastic left heart syndrome (HLHS) pathogenesis is confounded by its genetic heterogeneity and oligogenic underpinnings.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>\n              Whole genome sequences were analyzed by 3 independent strategies to identify\n              <jats:italic>HLHS<\/jats:italic>\n              gene candidates, ranked by variant, gene, and disease-level metrics.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              First, a genome-wide association study of 174 cases and 853 controls revealed suggestive association with a\n              <jats:italic>MYO18B<\/jats:italic>\n              intron 33 variant (rs2269628-G; frequency=0.55 versus 0.39; OR, 1.97 [95% CI, 1.54\u20132.52];\n              <jats:italic>P<\/jats:italic>\n              =6.70\u00d710\n              <jats:sup>\u2212<\/jats:sup>\n              <jats:sup>8<\/jats:sup>\n              ). Second, transmission disequilibrium testing of 161 HLHS proband-parent trios revealed overrepresentation of a\n              <jats:italic>MYO18B<\/jats:italic>\n              intron 42 variant (rs73154186-A; frequency=0.05; OR, 24 [95% CI, 3.2\u2013177.4];\n              <jats:italic>P<\/jats:italic>\n              =4.23\u00d710\n              <jats:sup>\u2212<\/jats:sup>\n              <jats:sup>6<\/jats:sup>\n              ). Third, rare, predicted-damaging variants were filtered in 2 multiplex families. In 141H, 2 fifth-degree relatives with HLHS shared a paternally-inherited\n              <jats:italic>MYO5A<\/jats:italic>\n              missense variant (p.Arg801Trp; frequency=0.00003; combined annotation-dependent depletion score=29), each with a maternally-inherited or de novo candidate modifier variant in a MYO5A-interacting conventional myosin. In 442H, a HLHS proband was compound heterozygous for\n              <jats:italic>MYO15A<\/jats:italic>\n              variants\u2014a maternally-inherited pathogenic stop-gain variant co-segregating with tetralogy of Fallot and bicuspid aortic valve in maternal relatives (p.Tyr2819Ter; frequency=0.00003) and a paternally-inherited intronic variant altering a canonical transcription factor binding site (rs1277068603; frequency=0.00001; position weight matrix score=0.98).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>\n              Collectively, these findings suggest that common and rare alleles within unconventional myosin genes are associated with HLHS susceptibility. The identified candidate\n              <jats:italic>MYO18B<\/jats:italic>\n              regulates cardiac sarcomerogenesis, supporting the hypothesis of intrinsic myogenic perturbation in arrested left heart development.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circgen.122.003761","type":"journal-article","created":{"date-parts":[[2022,12,29]],"date-time":"2022-12-29T16:24:21Z","timestamp":1672331061000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Genome-Wide Association and Inheritance-Based Analyses Implicate Unconventional Myosin Genes in Hypoplastic Left Heart Syndrome"],"prefix":"10.1161","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4494-8683","authenticated-orcid":true,"given":"Jeanne L.","family":"Theis","sequence":"first","affiliation":[{"name":"Cardiovascular Genetics Research Laboratory (J.L.T., T.M.O.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah-Dana H.","family":"Shatila","sequence":"additional","affiliation":[{"name":"Division of Clinical Trials and Biostatistics (S.-D.H.S., W.R.B.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5588-3216","authenticated-orcid":true,"given":"Zachary C.","family":"Fogarty","sequence":"additional","affiliation":[{"name":"Division of Computational Biology, Department of Quantitative Health Sciences (Z.C.F.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2903-1284","authenticated-orcid":true,"given":"William R.","family":"Bamlet","sequence":"additional","affiliation":[{"name":"Division of Clinical Trials and Biostatistics (S.-D.H.S., W.R.B.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2716-9423","authenticated-orcid":true,"given":"Timothy M.","family":"Olson","sequence":"additional","affiliation":[{"name":"Cardiovascular Genetics Research Laboratory (J.L.T., T.M.O.), Mayo Clinic, Rochester, MN."},{"name":"Division of Pediatric Cardiology, Department of Pediatric and Adolescent Medicine (T.M.O.), Mayo Clinic, Rochester, MN."},{"name":"Department of Cardiovascular Medicine (T.M.O.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2007.07.021"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2016.02.052"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30090"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp532"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3870"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2637"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu420"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddw071"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.116.001449"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehy142"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.038376"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI141837"},{"key":"e_1_3_3_14_2","first-page":"506","article-title":"Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM).","volume":"52","author":"Spielman RS","year":"1993","unstructured":"Spielman, RS, McGinnis, RE, Ewens, WJ. Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am J Hum Genet. 1993;52:506\u2013516.","journal-title":"Am J Hum Genet"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20049"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGEN.120.003126"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03940"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-015-1582-1"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGEN.118.002397"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.59554"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3970"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-38062-5_19"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2308-7"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.115.001070"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00091.2016"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-020-00762-2"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab466"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0133-9"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0171-3"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv402"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1262110"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.137323.112"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddz231"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jjcc.2014.12.022"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2003.05.004"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13302"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.120.316704"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2443.2008.01226.x"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108090"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.3233\/JND-150085"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGEN.121.003523"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.121.056198"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2013.06.006"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.806"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1086\/519795"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.09.004"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature15393"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq559"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/164.4.1567"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/155.2.945"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.9.8.677"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.21105\/joss.00731"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btab186"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/27.2.573"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-0974-4"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0089570"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2892"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks1221"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1754"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aac9396"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1081"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1100"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1056"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1120"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2017.01.004"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1131"}],"container-title":["Circulation: Genomic and Precision Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCGEN.122.003761","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T01:15:20Z","timestamp":1715562920000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCGEN.122.003761"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2]]},"references-count":67,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,2]]}},"alternative-id":["10.1161\/CIRCGEN.122.003761"],"URL":"https:\/\/doi.org\/10.1161\/circgen.122.003761","relation":{},"ISSN":["2574-8300"],"issn-type":[{"value":"2574-8300","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2]]},"assertion":[{"value":"2022-03-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}