{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T09:37:08Z","timestamp":1784885828011,"version":"3.55.0"},"reference-count":34,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,4,27]],"date-time":"2021-04-27T00:00:00Z","timestamp":1619481600000},"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"],"award-info":[{"award-number":["P01HD070454"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01-HL098153, HL128711, HL098188, HL131003, HL098147, HL098162, HL098162"],"award-info":[{"award-number":["U01-HL098153, HL128711, HL098188, HL131003, HL098147, HL098162, HL098162"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50HL74713, UL1RR02134, UL1TR000003"],"award-info":[{"award-number":["P50HL74713, UL1RR02134, UL1TR000003"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>There is strong evidence for a genetic contribution to non-syndromic congenital heart defects (CHDs). However, exome- and genome-wide studies conducted at the variant and gene-level have identified few genome-wide significant CHD-related genes. Gene-set analyses are a useful complement to such studies and candidate gene-set analyses of rare variants have provided insight into the genetics of CHDs. However, similar analyses have not been conducted using data on common genetic variants. Consequently, we conducted common variant analyses of 15 CHD candidate gene-sets, using data from two common types of CHDs: conotruncal heart defects (1431 cases) and left ventricular outflow tract defects (509 cases). After Bonferroni correction for evaluation of multiple gene-sets, the cytoskeletal gene-set was significantly associated with conotruncal heart defects (\u03b2S = 0.09; 95% confidence interval (CI) 0.03\u20130.15). This association was stronger when analyses were restricted to the sub-set of cytoskeletal genes that have been observed to harbor rare damaging genotypes in at least two CHD cases (\u03b2S = 0.32, 95% CI 0.08\u20130.56). These findings add to the evidence linking cytoskeletal genes to CHDs and suggest that, for cytoskeletal genes, common variation may contribute to the risk of CHDs.<\/jats:p>","DOI":"10.3390\/genes12050655","type":"journal-article","created":{"date-parts":[[2021,4,27]],"date-time":"2021-04-27T21:18:20Z","timestamp":1619558300000},"page":"655","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Common Variation in Cytoskeletal Genes Is Associated with Conotruncal Heart Defects"],"prefix":"10.3390","volume":"12","author":[{"given":"Fadi I.","family":"Musfee","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Human Genetics and Environmental Sciences, UTHealth School of Public Health, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Goldmuntz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hakon","family":"Hakonarson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Center for Applied Genomics, The Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernice E.","family":"Morrow","sequence":"additional","affiliation":[{"name":"Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3302-4610","authenticated-orcid":false,"given":"Deanne M.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Department of Biomedical and Health Informatics, The Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5916-442X","authenticated-orcid":false,"given":"Martin","family":"Tristani-Firouzi","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology, University of Utah School of Medicine, Salt Lake City, UT 84113, USA"},{"name":"Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT 84112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Scott","family":"Watkins","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Yandell","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA"},{"name":"Utah Center for Genetic Discovery, University of Utah, Salt Lake City, UT 84112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1161\/CIRCRESAHA.116.309302","article-title":"Changing Landscape of Congenital Heart Disease","volume":"120","author":"Bouma","year":"2017","journal-title":"Circ. 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