{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T07:15:27Z","timestamp":1765610127442,"version":"build-2065373602"},"reference-count":31,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01HD070454","R01HL084410","U01MH101720","R21HL118637","T32GM007491-41","R01MH085903","R01HD042974","R21HD060309-01"],"award-info":[{"award-number":["P01HD070454","R01HL084410","U01MH101720","R21HL118637","T32GM007491-41","R01MH085903","R01HD042974","R21HD060309-01"]}],"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","award":["P50-HL74731","U01-HL098147","U01-HL098188","U01-HL131003","U01-HL098153","U01-HL098163","U01-HL098123","U01-HL098162"],"award-info":[{"award-number":["P50-HL74731","U01-HL098147","U01-HL098188","U01-HL131003","U01-HL098153","U01-HL098163","U01-HL098123","U01-HL098162"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Cardiovascular Development Consortium","award":["U01-HL098166"],"award-info":[{"award-number":["U01-HL098166"]}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["U54-HG006504"],"award-info":[{"award-number":["U54-HG006504"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000097","name":"National Center for Research Resources","doi-asserted-by":"publisher","award":["M01-RR-000240","RR024134"],"award-info":[{"award-number":["M01-RR-000240","RR024134"]}],"id":[{"id":"10.13039\/100000097","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1-TR000003"],"award-info":[{"award-number":["UL1-TR000003"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["14PRE199800006"],"award-info":[{"award-number":["14PRE199800006"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fondo National de Desarrollo Cientifico y Tecnologico-Chile","award":["1100131","1130392"],"award-info":[{"award-number":["1100131","1130392"]}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["97800","89066"],"award-info":[{"award-number":["97800","89066"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["324730_121996","324730_144260"],"award-info":[{"award-number":["324730_121996","324730_144260"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Conotruncal defects with normally related great vessels (CTD-NRGVs) occur in both patients with and without 22q11.2 deletion syndrome (22q11.2DS), but it is unclear to what extent the genetically complex etiologies of these heart defects may overlap across these two groups, potentially involving variation within and\/or outside of the 22q11.2 region. To explore this potential overlap, we conducted genome-wide SNP-level, gene-level, and gene set analyses using common variants, separately in each of five cohorts, including two with 22q11.2DS (N = 1472 total cases) and three without 22q11.2DS (N = 935 total cases). Results from the SNP-level analyses were combined in meta-analyses, and summary statistics from these analyses were also used in gene and gene set analyses. Across all these analyses, no association was significant after correction for multiple comparisons. However, several SNPs, genes, and gene sets with suggestive evidence of association were identified. For common inherited variants, we did not identify strong evidence for shared genomic mechanisms for CTD-NRGVs across individuals with and without 22q11.2 deletions. Nevertheless, several of our top gene-level and gene set results have been linked to cardiogenesis and may represent candidates for future work.<\/jats:p>","DOI":"10.3390\/genes12071030","type":"journal-article","created":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T12:03:27Z","timestamp":1625141007000},"page":"1030","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Genome-Wide Association Studies of Conotruncal Heart Defects with Normally Related Great Vessels in the United States"],"prefix":"10.3390","volume":"12","author":[{"given":"Omobola O.","family":"Oluwafemi","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Human Genetics and Environmental Sciences, UTHealth School of Public Health, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fadi I.","family":"Musfee","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Human Genetics and Environmental Sciences, UTHealth School of Public Health, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura E.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Human Genetics and Environmental Sciences, UTHealth School of Public Health, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Goldmuntz","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"},{"name":"Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongbo M.","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Health Informatics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2814-7461","authenticated-orcid":false,"given":"Hakon","family":"Hakonarson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA"},{"name":"Center for Applied Genomics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernice E.","family":"Morrow","sequence":"additional","affiliation":[{"name":"Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingwei","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deanne M.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA"},{"name":"Department of Biomedical and Health Informatics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4077-250X","authenticated-orcid":false,"given":"Donna M.","family":"McDonald-McGinn","sequence":"additional","affiliation":[{"name":"Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA"},{"name":"Division of Human Genetics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beverly S.","family":"Emanuel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA"},{"name":"Division of Human Genetics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. J.","family":"Agopian","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Human Genetics and Environmental Sciences, UTHealth School of Public Health, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,1]]},"reference":[{"key":"ref_1","first-page":"100685","article-title":"Neurodevelopmental outcomes of children with congenital heart disease: A review","volume":"49","author":"Howell","year":"2019","journal-title":"Curr. Probl. Pediatr. Adolesc. Health Care"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s00246-019-02271-4","article-title":"Genetic Contribution to Congenital Heart Disease (CHD)","volume":"41","author":"Shabana","year":"2020","journal-title":"Pediatr. 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