{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T06:27:57Z","timestamp":1720765677142},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2013,6,19]],"date-time":"2013-06-19T00:00:00Z","timestamp":1371600000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/2.0"},{"start":{"date-parts":[[2013,6,19]],"date-time":"2013-06-19T00:00:00Z","timestamp":1371600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/2.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Genet"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Epidemiological studies indicate a substantial excess familial recurrence of non-syndromic Tetralogy of Fallot (TOF), implicating genetic factors that remain largely unknown. The Rho induced kinase 1 gene (ROCK1) is a key component of the planar cell polarity signalling pathway, which plays an important role in normal cardiac development. The aim of this study was to investigate the role of genetic variation in ROCK1 on the risk of TOF.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>ROCK1 was sequenced in a discovery cohort of 93 non-syndromic TOF probands to identify rare variants. TagSNPs were selected to capture commoner variation in ROCK1. Novel variants and TagSNPs were genotyped in a discovery cohort of 458 TOF cases and 1331 healthy controls, and positive findings were replicated in a further 209 TOF cases and 1290 healthy controls. Association between genotypes and TOF was assessed using LAMP.<\/jats:p>\n            <jats:p>A rare SNP (c.807C\u2009&gt;\u2009T; rs56085230) discovered by sequencing was associated with TOF risk (p\u2009=\u20090.006) in the discovery cohort. The variant was also significantly associated with the risk of TOF in the replication cohort (p\u2009=\u20090.018). In the combined cohorts the odds ratio for TOF was 2.61 (95% CI 1.58-4.30); p\u2009&lt;\u20090.0001. The minor allele frequency of rs56085230 in the cases was 0.02, and in the controls it was 0.007. The variant accounted for 1% of the population attributable risk (PAR) of TOF. We also found significant association with TOF for an uncommon TagSNP in ROCK1, rs288979 (OR 1.64 [95% CI 1.15-2.30]; p\u2009=\u20091.5x10<jats:sup>-5<\/jats:sup>). The minor allele frequency of rs288979 in the controls was 0.043, and the variant accounted for 11% of the PAR of TOF. These association signals were independent of each other, providing additional internal validation of our result.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Low frequency intermediate penetrance (LFIP) variants in the ROCK1 gene predispose to the risk of TOF.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2156-14-57","type":"journal-article","created":{"date-parts":[[2013,6,19]],"date-time":"2013-06-19T08:14:43Z","timestamp":1371629683000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Low-frequency intermediate penetrance variants in the ROCK1 gene predispose to Tetralogy of Fallot"],"prefix":"10.1186","volume":"14","author":[{"given":"Julian","family":"Palomino Doza","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Topf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jamie","family":"Bentham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shoumo","family":"Bhattacharya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Cosgrove","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J David","family":"Brook","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Granados-Riveron","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frances A","family":"Bu\u2019Lock","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"O\u2019Sullivan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A Graham","family":"Stuart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Parsons","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Relton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judith","family":"Goodship","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah J","family":"Henderson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernard","family":"Keavney","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2013,6,19]]},"reference":[{"issue":"9699","key":"1133_CR1","doi-asserted-by":"publisher","first-page":"1462","DOI":"10.1016\/S0140-6736(09)60657-7","volume":"374","author":"C Apitz","year":"2009","unstructured":"Apitz C, Webb GD, Redington AN: Tetralogy of Fallot. Lancet. 2009, 374 (9699): 1462-1471. 10.1016\/S0140-6736(09)60657-7.","journal-title":"Lancet"},{"issue":"9099","key":"1133_CR2","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/S0140-6736(97)06486-6","volume":"351","author":"J Burn","year":"1998","unstructured":"Burn J, Brennan P, Little J, Holloway S, Coffey R, Somerville J, Dennis NR, Allan L, Arnold R, Deanfield JE, et al: Recurrence risks in offspring of adults with major heart defects: results from first cohort of British collaborative study. Lancet. 1998, 351 (9099): 311-316. 10.1016\/S0140-6736(97)06486-6.","journal-title":"Lancet"},{"issue":"2","key":"1133_CR3","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1136\/jmg.9.2.179","volume":"9","author":"AR Boon","year":"1972","unstructured":"Boon AR, Farmer MB, Roberts DF: A family study of Fallot\u2019s tetralogy. J Med Genet. 1972, 9 (2): 179-192. 10.1136\/jmg.9.2.179.","journal-title":"J Med Genet"},{"issue":"21","key":"1133_CR4","doi-asserted-by":"publisher","first-page":"2565","DOI":"10.1161\/hc4601.098427","volume":"104","author":"E Goldmuntz","year":"2001","unstructured":"Goldmuntz E, Geiger E, Benson DW: NKX2.5 mutations in patients with tetralogy of fallot. Circulation. 2001, 104 (21): 2565-2568. 10.1161\/hc4601.098427.","journal-title":"Circulation"},{"issue":"20","key":"1133_CR5","doi-asserted-by":"publisher","first-page":"1651","DOI":"10.1136\/hrt.2010.200121","volume":"96","author":"HR Griffin","year":"2010","unstructured":"Griffin HR, Topf A, Glen E, Zweier C, Stuart AG, Parsons J, Peart I, Deanfield J, O\u2019Sullivan J, Rauch A, et al: Systematic survey of variants in TBX1 in non-syndromic tetralogy of Fallot identifies a novel 57 base pair deletion that reduces transcriptional activity but finds no evidence for association with common variants. Heart. 2010, 96 (20): 1651-1655. 10.1136\/hrt.2010.200121.","journal-title":"Heart"},{"issue":"8","key":"1133_CR6","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1038\/ng.415","volume":"41","author":"SC Greenway","year":"2009","unstructured":"Greenway SC, Pereira AC, Lin JC, DePalma SR, Israel SJ, Mesquita SM, Ergul E, Conta JH, Korn JM, McCarroll SA, et al: De novo copy number variants identify new genes and loci in isolated sporadic tetralogy of Fallot. Nat Genet. 2009, 41 (8): 931-935. 10.1038\/ng.415.","journal-title":"Nat Genet"},{"issue":"7","key":"1133_CR7","doi-asserted-by":"publisher","first-page":"1513","DOI":"10.1093\/hmg\/ddr589","volume":"21","author":"R Soemedi","year":"2012","unstructured":"Soemedi R, Topf A, Wilson IJ, Darlay R, Rahman T, Glen E, Hall D, Huang N, Bentham J, Bhattacharya S, et al: Phenotype-specific effect of chromosome 1q21.1 rearrangements and GJA5 duplications in 2436 congenital heart disease patients and 6760 controls. Hum Mol Genet. 2012, 21 (7): 1513-1520. 10.1093\/hmg\/ddr589.","journal-title":"Hum Mol Genet"},{"issue":"3","key":"1133_CR8","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1161\/CIRCGENETICS.111.962035","volume":"5","author":"JA Goodship","year":"2012","unstructured":"Goodship JA, Hall D, Topf A, Mamasoula C, Griffin H, Rahman TJ, Glen E, Tan H, Palomino Doza J, Relton CL, et al: Common Variant in the PTPN11 Gene Contributes to the Risk of Tetralogy of Fallot. Circ Cardiovasc Genet. 2012, 5 (3): 287-292. 10.1161\/CIRCGENETICS.111.962035.","journal-title":"Circ Cardiovasc Genet"},{"issue":"2","key":"1133_CR9","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.cardiores.2006.06.025","volume":"72","author":"T Brade","year":"2006","unstructured":"Brade T, Manner J, Kuhl M: The role of Wnt signalling in cardiac development and tissue remodelling in the mature heart. Cardiovasc Res. 2006, 72 (2): 198-209. 10.1016\/j.cardiores.2006.06.025.","journal-title":"Cardiovasc Res"},{"issue":"2","key":"1133_CR10","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.tcm.2005.11.005","volume":"16","author":"DJ Henderson","year":"2006","unstructured":"Henderson DJ, Phillips HM, Chaudhry B: Vang-like 2 and noncanonical Wnt signalling in outflow tract development. Trends Cardiovasc Med. 2006, 16 (2): 38-45. 10.1016\/j.tcm.2005.11.005.","journal-title":"Trends Cardiovasc Med"},{"issue":"1","key":"1133_CR11","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1002\/dvdy.10212","volume":"226","author":"Z Zhao","year":"2003","unstructured":"Zhao Z, Rivkees SA: Rho-associated kinases play an essential role in cardiac morphogenesis and cardiomyocyte proliferation. Dev Dyn. 2003, 226 (1): 24-32. 10.1002\/dvdy.10212.","journal-title":"Dev Dyn"},{"issue":"1","key":"1133_CR12","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1002\/dvdy.20648","volume":"235","author":"M Sakabe","year":"2006","unstructured":"Sakabe M, Ikeda K, Nakatani K, Kawada N, Imanaka-Yoshida K, Yoshida T, Yamagishi T, Nakajima Y: Rho kinases regulate endothelial invasion and migration during valvuloseptal endocardial cushion tissue formation. Dev Dyn. 2006, 235 (1): 94-104. 10.1002\/dvdy.20648.","journal-title":"Dev Dyn"},{"issue":"6","key":"1133_CR13","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1083\/jcb.200411179","volume":"168","author":"Y Shimizu","year":"2005","unstructured":"Shimizu Y, Thumkeo D, Keel J, Ishizaki T, Oshima H, Oshima M, Noda Y, Matsumura F, Taketo MM, Narumiya S: ROCK-I regulates closure of the eyelids and ventral body wall by inducing assembly of actomyosin bundles. J Cell Biol. 2005, 168 (6): 941-953. 10.1083\/jcb.200411179.","journal-title":"J Cell Biol"},{"issue":"16","key":"1133_CR14","doi-asserted-by":"publisher","first-page":"2903","DOI":"10.1242\/dev.007542","volume":"134","author":"VL Ruiz-Perez","year":"2007","unstructured":"Ruiz-Perez VL, Blair HJ, Rodriguez-Andres ME, Blanco MJ, Wilson A, Liu YN, Miles C, Peters H, Goodship JA: Evc is a positive mediator of Ihh-regulated bone growth that localises at the base of chondrocyte cilia. Development. 2007, 134 (16): 2903-2912. 10.1242\/dev.007542.","journal-title":"Development"},{"issue":"6","key":"1133_CR15","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1136\/jmg.2004.027631","volume":"42","author":"N Gaukrodger","year":"2005","unstructured":"Gaukrodger N, Mayosi BM, Imrie H, Avery P, Baker M, Connell JM, Watkins H, Farrall M, Keavney B, Connell JMC: A rare variant of the leptin gene has large effects on blood pressure and carotid intima-medial thickness: a study of 1428 individuals in 248 families. J Med Genet. 2005, 42 (6): 474-478. 10.1136\/jmg.2004.027631.","journal-title":"J Med Genet"},{"issue":"5","key":"1133_CR16","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1136\/jmg.35.5.413","volume":"35","author":"DS Chase","year":"1998","unstructured":"Chase DS, Tawn EJ, Parker L, Jonas P, Parker CO, Burn J: The North Cumbria Community Genetics Project. J Med Genet. 1998, 35 (5): 413-416. 10.1136\/jmg.35.5.413.","journal-title":"J Med Genet"},{"issue":"16","key":"1133_CR17","doi-asserted-by":"publisher","first-page":"3445","DOI":"10.1093\/bioinformatics\/bti529","volume":"21","author":"JE Wigginton","year":"2005","unstructured":"Wigginton JE, Abecasis GR: PEDSTATS: descriptive statistics, graphics and quality assessment for gene mapping data. Bioinformatics. 2005, 21 (16): 3445-3447. 10.1093\/bioinformatics\/bti529.","journal-title":"Bioinformatics"},{"issue":"6","key":"1133_CR18","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1086\/430277","volume":"76","author":"M Li","year":"2005","unstructured":"Li M, Boehnke M, Abecasis GR: Joint modelling of linkage and association: identifying SNPs responsible for a linkage signal. Am J Hum Genet. 2005, 76 (6): 934-949. 10.1086\/430277.","journal-title":"Am J Hum Genet"},{"key":"1133_CR19","doi-asserted-by":"publisher","first-page":"2013","DOI":"10.1214\/aos\/1074290335","volume":"31","author":"J Storey","year":"2003","unstructured":"Storey J: The positive palse discovery rate: A bayesian interpretation and the q-value. Ann Stat. 2003, 31: 2013-2035. 10.1214\/aos\/1074290335.","journal-title":"Ann Stat"},{"key":"1133_CR20","doi-asserted-by":"publisher","first-page":"3568","DOI":"10.1093\/nar\/gkg616","volume":"31","author":"L Cartegni","year":"2003","unstructured":"Cartegni L, Wang J, Zhu Z, Zhang MQ, Krainer AR: ESEfinder: a web resource to identify exonic splicing enhancers. Nucleic Acids Res. 2003, 31: 3568-3571. 10.1093\/nar\/gkg616.","journal-title":"Nucleic Acids Res"},{"key":"1133_CR21","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1002\/humu.20151","volume":"25","author":"VK Nalla","year":"2005","unstructured":"Nalla VK, Rogan PK: Automated splicing mutation analysis by information theory. Hum Mutat. 2005, 25: 334-342. 10.1002\/humu.20151.","journal-title":"Hum Mutat"},{"key":"1133_CR22","doi-asserted-by":"publisher","first-page":"D64","DOI":"10.1093\/nar\/gks1048","volume":"41","author":"LR Meyer","year":"2012","unstructured":"Meyer LR, Zweig AS, Hinrichs AS, Karolchik D, Kuhn RM, Wong M, Sloan CA, Rosenbloom KR, Roe G, Rhead B, et al: The UCSC Genome Browser database: extensions and updates 2013. Nucleic Acids Res. 2012, 41: D64-69.","journal-title":"Nucleic Acids Res"},{"issue":"20","key":"1133_CR23","doi-asserted-by":"publisher","first-page":"2417","DOI":"10.1093\/hmg\/11.20.2417","volume":"11","author":"JK Pritchard","year":"2002","unstructured":"Pritchard JK, Cox NJ: The allelic architecture of human disease genes: common disease-common variant\u2026or not?. Hum Mol Genet. 2002, 11 (20): 2417-2423. 10.1093\/hmg\/11.20.2417.","journal-title":"Hum Mol Genet"},{"issue":"1","key":"1133_CR24","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1086\/321272","volume":"69","author":"JK Pritchard","year":"2001","unstructured":"Pritchard JK: Are rare variants responsible for susceptibility to complex diseases?. Am J Hum Genet. 2001, 69 (1): 124-137. 10.1086\/321272.","journal-title":"Am J Hum Genet"},{"issue":"4","key":"1133_CR25","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1086\/513473","volume":"80","author":"GV Kryukov","year":"2007","unstructured":"Kryukov GV, Pennacchio LA, Sunyaev SR, Kryukov GV, Pennacchio LA, Sunyaev SR: Most rare missense alleles are deleterious in humans: implications for complex disease and association studies. Am J Hum Genet. 2007, 80 (4): 727-739. 10.1086\/513473.","journal-title":"Am J Hum Genet"},{"issue":"9","key":"1133_CR26","doi-asserted-by":"publisher","first-page":"1202","DOI":"10.2105\/AJPH.85.9.1202","volume":"85","author":"ME Northridge","year":"1995","unstructured":"Northridge ME: Public health methods\u2013attributable risk as a link between causality and public health action. Am J Public Health. 1995, 85 (9): 1202-1204. 10.2105\/AJPH.85.9.1202.","journal-title":"Am J Public Health"}],"container-title":["BMC Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2156-14-57.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/1471-2156-14-57\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2156-14-57.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T00:53:16Z","timestamp":1630543996000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcgenet.biomedcentral.com\/articles\/10.1186\/1471-2156-14-57"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,6,19]]},"references-count":26,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,12]]}},"alternative-id":["1133"],"URL":"https:\/\/doi.org\/10.1186\/1471-2156-14-57","relation":{},"ISSN":["1471-2156"],"issn-type":[{"value":"1471-2156","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,6,19]]},"assertion":[{"value":"13 June 2012","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 June 2013","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 June 2013","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"57"}}