{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T01:48:05Z","timestamp":1788227285700,"version":"build-2803163510"},"update-to":[{"DOI":"10.12688\/f1000research.19571.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2019,7,19]],"date-time":"2019-07-19T00:00:00Z","timestamp":1563494400000}}],"reference-count":65,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2019,7,19]],"date-time":"2019-07-19T00:00:00Z","timestamp":1563494400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005416","name":"Norges Forskningsr\u00e5d","doi-asserted-by":"publisher","award":["245464"],"award-info":[{"award-number":["245464"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005416","name":"Norges Forskningsr\u00e5d","doi-asserted-by":"publisher","award":["262700"],"award-info":[{"award-number":["262700"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006475","name":"Bergens Forskningsstiftelse","doi-asserted-by":"publisher","award":["807191"],"award-info":[{"award-number":["807191"]}],"id":[{"id":"10.13039\/501100006475","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>\n                    <ns4:bold>Background:<\/ns4:bold>\n                    Although both genetic and environmental factors have been reported to influence the risk of isolated cleft lip with or without cleft palate (CL\/P), the exact mechanisms behind CL\/P are still largely unaccounted for. We recently developed new methods to identify parent-of-origin (PoO) interactions with environmental exposures (PoOxE) and now apply them to data from a genome-wide association study (GWAS) of families with children born with isolated CL\/P.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Methods:<\/ns4:bold>\n                    Genotypes from 1594 complete triads and 314 dyads (1908 nuclear families in total) with CL\/P were available for the current analyses. Of these families, 1024 were Asian, 825 were European and 59 had other ancestries. After quality control, 341,191 SNPs remained from the original 569,244. The exposures were maternal cigarette smoking, use of alcohol, and use of vitamin supplements in the periconceptional period. Our new methodology detects if PoO effects are different across environmental strata and is implemented in the\n                    <ns4:italic>R<\/ns4:italic>\n                    -package Haplin.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Results:<\/ns4:bold>\n                    Among Europeans, there was evidence of a PoOxSmoke effect for\n                    <ns4:italic>ANK3<\/ns4:italic>\n                    with three SNPs (rs3793861, q=0.20, p=2.6e-6; rs7087489, q=0.20, p=3.1e-6; rs4310561, q=0.67, p=4.0e-5) and a PoOxAlcohol effect for\n                    <ns4:italic>ARHGEF10<\/ns4:italic>\n                    with two SNPs (rs2294035, q=0.32, p=2.9e-6; rs4876274, q=0.76, p=1.3e-5).\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Conclusion:<\/ns4:bold>\n                    Our results indicate that the detected PoOxE effects have a plausible biological basis, and thus warrant replication in other independent cleft samples. Our demonstration of the feasibility of identifying complex interactions between relevant environmental exposures and PoO effects offers new avenues for future research aimed at unravelling the complex etiology of cleft lip defects.\n                  <\/ns4:p>","DOI":"10.12688\/f1000research.19571.2","type":"journal-article","created":{"date-parts":[[2019,7,19]],"date-time":"2019-07-19T05:15:39Z","timestamp":1563513339000},"page":"960","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["A genome-wide scan of cleft lip triads identifies parent-of-origin interaction effects between ANK3 and maternal smoking, and between ARHGEF10 and alcohol consumption"],"prefix":"10.12688","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5288-7879","authenticated-orcid":false,"given":"\u00d8ystein Ariansen","family":"Haaland","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Romanowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Gjerdevik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolv Terje","family":"Lie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3544-1063","authenticated-orcid":false,"given":"H\u00e5kon Kristian","family":"Gjessing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astanand","family":"Jugessur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2019,7,19]]},"reference":[{"key":"ref-1","article-title":"Global registry and database on craniofacial anomalies","author":"P Mossey","year":"2003"},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"1063-1070","DOI":"10.1001\/jamapediatrics.2016.1925","article-title":"Health Status Among Adults Born With an Oral Cleft in Norway.","volume":"170","author":"E Berg","year":"2016","journal-title":"JAMA Pediatr."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"e0162196","DOI":"10.1371\/journal.pone.0162196","article-title":"Socio-Economic Status and Reproduction among Adults Born with an Oral Cleft: A Population-Based Cohort Study in Norway.","volume":"11","author":"E Berg","year":"2016","journal-title":"PLoS One."},{"key":"ref-4","doi-asserted-by":"publisher","first-page":"189-195","DOI":"10.1597\/1545-1569_1999_036_0189_toadoc_2.3.co_2","article-title":"The organization and delivery of craniofacial health Services: the state of the art.","volume":"36","author":"R Strauss","year":"1999","journal-title":"Cleft Palate Craniofac J."},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"3-10","DOI":"10.1111\/j.1601-0825.2009.01588.x","article-title":"The impact of orofacial clefts on quality of life and healthcare use and costs.","volume":"16","author":"G Wehby","year":"2010","journal-title":"Oral Dis."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"73-91","DOI":"10.1597\/10-178","article-title":"Genetics of nonsyndromic orofacial clefts.","volume":"49","author":"F Rahimov","year":"2012","journal-title":"Cleft Palate Craniofac J."},{"key":"ref-7","doi-asserted-by":"publisher","first-page":"167-178","DOI":"10.1038\/nrg2933","article-title":"Cleft lip and palate: understanding genetic and environmental influences.","volume":"12","author":"M Dixon","year":"2011","journal-title":"Nat Rev Genet."},{"key":"ref-8","doi-asserted-by":"publisher","first-page":"437-453","DOI":"10.1111\/j.1601-0825.2009.01577.x","article-title":"The genetics of isolated orofacial clefts: from genotypes to subphenotypes.","volume":"15","author":"A Jugessur","year":"2009","journal-title":"Oral Dis."},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"263-283","DOI":"10.1146\/annurev-genom-090711-163729","article-title":"The evolution of human genetic studies of cleft lip and cleft palate.","volume":"13","author":"M Marazita","year":"2012","journal-title":"Annu Rev Genomics Hum Genet."},{"key":"ref-10","doi-asserted-by":"publisher","first-page":"220-232","DOI":"10.1002\/dvdy.24341","article-title":"Toward an orofacial gene regulatory network.","volume":"245","author":"Y Kousa","year":"2016","journal-title":"Dev Dyn."},{"key":"ref-11","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1038\/ng0810-727","article-title":"Erratum: A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4.","volume":"42","author":"T Beaty","year":"2010","journal-title":"Nat Genet."},{"key":"ref-12","doi-asserted-by":"publisher","first-page":"473-477","DOI":"10.1038\/ng.333","article-title":"Key susceptibility locus for nonsyndromic cleft lip with or without cleft palate on chromosome 8q24.","volume":"41","author":"S Birnbaum","year":"2009","journal-title":"Nat Genet."},{"key":"ref-13","doi-asserted-by":"publisher","first-page":"510-514","DOI":"10.1016\/j.ejmg.2012.06.005","article-title":"GWAS reveals new recessive loci associated with non-syndromic facial clefting.","volume":"55","author":"M Camargo","year":"2012","journal-title":"Eur J Med Genet."},{"key":"ref-14","doi-asserted-by":"publisher","first-page":"909-913","DOI":"10.1016\/j.jpeds.2009.06.020","article-title":"A genome-wide association study identifies a locus for nonsyndromic cleft lip with or without cleft palate on 8q24.","volume":"155","author":"S Grant","year":"2009","journal-title":"J Pediatr."},{"key":"ref-15","doi-asserted-by":"publisher","first-page":"24-26","DOI":"10.1038\/ng.506","article-title":"Genome-wide association study identifies two susceptibility loci for nonsyndromic cleft lip with or without cleft palate.","volume":"42","author":"E Mangold","year":"2010","journal-title":"Nat Genet."},{"key":"ref-16","doi-asserted-by":"publisher","first-page":"968-971","DOI":"10.1038\/ng.2360","article-title":"Genome-wide meta-analyses of nonsyndromic cleft lip with or without cleft palate identify six new risk loci.","volume":"44","author":"K Ludwig","year":"2012","journal-title":"Nat Genet."},{"key":"ref-17","doi-asserted-by":"publisher","first-page":"2468-2474","DOI":"10.1002\/ajmg.a.33608","article-title":"Recurrence risk for offspring of twins discordant for oral cleft: a population-based cohort study of the Danish 1936-2004 cleft twin cohort.","volume":"152A","author":"D Grosen","year":"2010","journal-title":"Am J Med Genet A."},{"key":"ref-18","doi-asserted-by":"publisher","first-page":"162-168","DOI":"10.1136\/jmg.2009.069385","article-title":"A cohort study of recurrence patterns among more than 54,000 relatives of oral cleft cases in Denmark: support for the multifactorial threshold model of inheritance.","volume":"47","author":"D Grosen","year":"2010","journal-title":"J Med Genet."},{"key":"ref-19","doi-asserted-by":"publisher","first-page":"313-319","DOI":"10.1097\/EDE.0b013e3182125f9c","article-title":"Risk of oral clefts in twins.","volume":"22","author":"D Grosen","year":"2011","journal-title":"Epidemiology."},{"key":"ref-20","doi-asserted-by":"publisher","first-page":"432-4","DOI":"10.1136\/bmj.39458.563611.AE","article-title":"Familial risk of oral clefts by morphological type and severity: population based cohort study of first degree relatives.","volume":"336","author":"A Sivertsen","year":"2008","journal-title":"BMJ."},{"key":"ref-21","doi-asserted-by":"publisher","first-page":"609-617","DOI":"10.1038\/nrg3543","article-title":"Genomic imprinting and parent-of-origin effects on complex traits.","volume":"14","author":"H Lawson","year":"2013","journal-title":"Nat Rev Genet."},{"key":"ref-22","first-page":"664-665","article-title":"Parent-of-Origin-Environment Interactions in Case-Parent Triads With or Without Independent Controls.","volume":"41","author":"M Gjerdevik","year":"2017","journal-title":"Genet Epidemiol."},{"key":"ref-23","doi-asserted-by":"publisher","first-page":"201-209","DOI":"10.1111\/j.1399-0004.2011.01790.x","article-title":"Parent of origin effects.","volume":"81","author":"A Guilmatre","year":"2012","journal-title":"Clin Genet."},{"key":"ref-24","doi-asserted-by":"publisher","first-page":"517-530","DOI":"10.1038\/nrg3766","article-title":"The role of genomic imprinting in biology and disease: an expanding view.","volume":"15","author":"J Peters","year":"2014","journal-title":"Nat Rev Genet."},{"key":"ref-25","doi-asserted-by":"publisher","first-page":"259-272","DOI":"10.1038\/nrg2764","article-title":"Gene--environment-wide association studies: emerging approaches.","volume":"11","author":"D Thomas","year":"2010","journal-title":"Nat Rev Genet."},{"key":"ref-26","doi-asserted-by":"publisher","first-page":"382-396","DOI":"10.1111\/j.1529-8817.2005.00218.x","article-title":"Case-parent triads: estimating single- and double-dose effects of fetal and maternal disease gene haplotypes.","volume":"70","author":"H Gjessing","year":"2006","journal-title":"Ann Hum Genet."},{"key":"ref-27","doi-asserted-by":"publisher","first-page":"e0184358","DOI":"10.1371\/journal.pone.0184358","article-title":"Genome-wide analysis of parent-of-origin interaction effects with environmental exposure (PoOxE): An application to European and Asian cleft palate trios.","volume":"12","author":"O Haaland","year":"2017","journal-title":"PLoS One."},{"key":"ref-28","doi-asserted-by":"publisher","first-page":"60","DOI":"10.3389\/fgene.2018.00060","article-title":"A Genome-Wide Search for Gene-Environment Effects in Isolated Cleft Lip with or without Cleft Palate Triads Points to an Interaction between Maternal Periconceptional Vitamin Use and Variants in ESRRG.","volume":"9","author":"A Haaland","year":"2018","journal-title":"Front Genet."},{"key":"ref-29","doi-asserted-by":"publisher","first-page":"887-893","DOI":"10.1086\/429864","article-title":"A note on exact tests of Hardy-Weinberg equilibrium.","volume":"76","author":"J Wigginton","year":"2005","journal-title":"Am J Hum Genet."},{"key":"ref-30","article-title":"R: A Language and Environment for Statistical Computing","year":"2017"},{"key":"ref-31","doi-asserted-by":"publisher","first-page":"221-236","DOI":"10.1111\/j.1469-1809.2012.00707.x","article-title":"Application of a novel hybrid study design to explore gene-environment interactions in orofacial clefts.","volume":"76","author":"O Skare","year":"2012","journal-title":"Ann Hum Genet."},{"key":"ref-32","doi-asserted-by":"publisher","first-page":"9440-9445","DOI":"10.1073\/pnas.1530509100","article-title":"Statistical significance for genomewide studies.","volume":"100","author":"J Storey","year":"2003","journal-title":"Proc Natl Acad Sci U S A."},{"key":"ref-33","article-title":"qvalue: Q-value estimation for false discovery rate control","author":"J Storey","year":"2015"},{"key":"ref-34","first-page":"305-307","article-title":"Retire statistical significance.","volume":"567","author":"V Amrhein","year":"2019","journal-title":"Nature."},{"key":"ref-35","doi-asserted-by":"publisher","first-page":"1-19","DOI":"10.1080\/00031305.2019.1583913","article-title":"Moving to a World Beyond \"p < 0.05\".","volume":"73","author":"R Wasserstein","year":"2019","journal-title":"Am Stat."},{"key":"ref-36","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1186\/s12859-019-2727-3","article-title":"Haplin power analysis: a software module for power and sample size calculations in genetic association analyses of family triads and unrelated controls.","volume":"20","author":"M Gjerdevik","year":"2019","journal-title":"BMC Bioinformatics."},{"key":"ref-37","doi-asserted-by":"publisher","first-page":"2336-2337","DOI":"10.1093\/bioinformatics\/btq419","article-title":"LocusZoom: regional visualization of genome-wide association scan results.","volume":"26","author":"R Pruim","year":"2010","journal-title":"Bioinformatics."},{"key":"ref-38","article-title":"A genome-wide scan of cleft lip triads identifies parent-of-origin interaction effects between ANK3 and maternal smoking, and between ARHGEF10 and alcohol consumption.","author":"A Haaland","year":"2019","journal-title":"Zenodo."},{"key":"ref-39","doi-asserted-by":"publisher","first-page":"D447-452","DOI":"10.1093\/nar\/gku1003","article-title":"STRING v10: protein-protein interaction networks, integrated over the tree of life.","volume":"43","author":"D Szklarczyk","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref-40","doi-asserted-by":"publisher","first-page":"D746-752","DOI":"10.1093\/nar\/gkv1045","article-title":"Expression Atlas update--an integrated database of gene and protein expression in humans, animals and plants.","volume":"44","author":"R Petryszak","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref-41","doi-asserted-by":"publisher","first-page":"2748","DOI":"10.12688\/f1000research.9973.1","article-title":"BgeeDB, an R package for retrieval of curated expression datasets and for gene list expression localization enrichment tests [version 1; peer review: 1 approved, 1 approved with reservations, 1 not approved].","volume":"5","author":"A Komljenovic","year":"2016","journal-title":"F1000Res."},{"key":"ref-42","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.26726","article-title":"Systematic integration of biomedical knowledge prioritizes drugs for repurposing.","volume":"6","author":"D Himmelstein","year":"2017","journal-title":"eLife."},{"key":"ref-43","doi-asserted-by":"publisher","first-page":"525-529","DOI":"10.1038\/ng.580","article-title":"A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4.","volume":"42","author":"T Beaty","year":"2010","journal-title":"Nat Genet."},{"key":"ref-44","first-page":"679-684","article-title":"Involvement of the CREB5 regulatory network in colorectal cancer metastasis.","volume":"36","author":"L Qi","year":"2014","journal-title":"Yi Chuan."},{"key":"ref-45","doi-asserted-by":"publisher","first-page":"9759-9769","DOI":"10.1074\/jbc.RA118.002743","article-title":"Differential activities and mechanisms of the four R-spondins in potentiating Wnt\/\u03b2-catenin signaling.","volume":"293","author":"S Park","year":"2018","journal-title":"J Biol Chem."},{"key":"ref-46","doi-asserted-by":"publisher","first-page":"1821-1830","DOI":"10.1242\/dev.075796","article-title":"Wnt9b-dependent FGF signaling is crucial for outgrowth of the nasal and maxillary processes during upper jaw and lip development.","volume":"139","author":"Y Jin","year":"2012","journal-title":"Development."},{"key":"ref-47","doi-asserted-by":"publisher","first-page":"511-519","DOI":"10.1016\/j.ydbio.2010.12.021","article-title":"Epithelial Wnt\/\u03b2-catenin signaling regulates palatal shelf fusion through regulation of Tgf\u03b23 expression.","volume":"350","author":"F He","year":"2011","journal-title":"Dev Biol."},{"key":"ref-48","doi-asserted-by":"publisher","first-page":"e898","DOI":"10.1038\/cddis.2013.424","article-title":"Retinoic acid alters the proliferation and survival of the epithelium and mesenchyme and suppresses Wnt\/\u03b2-catenin signaling in developing cleft palate.","volume":"4","author":"X Hu","year":"2013","journal-title":"Cell Death Dis."},{"key":"ref-49","doi-asserted-by":"publisher","first-page":"5339-5344","DOI":"10.3892\/etm.2017.5240","article-title":"Wnt6 influences the viability of mouse embryonic palatal mesenchymal cells via the \u03b2-catenin pathway.","volume":"14","author":"Z Jiang","year":"2017","journal-title":"Exp Ther Med."},{"key":"ref-50","doi-asserted-by":"publisher","first-page":"1371-1379","DOI":"10.1016\/S0140-6736(12)62129-1","article-title":"Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis.","volume":"381","year":"2013","journal-title":"Lancet."},{"key":"ref-51","doi-asserted-by":"publisher","DOI":"10.15363\/thinklab.d67","article-title":"Mining knowledge from MEDLINE articles and their indexed MeSH terms","author":"D Himmelstein","year":"2015"},{"key":"ref-52","doi-asserted-by":"publisher","first-page":"4212","DOI":"10.1038\/ncomms5212","article-title":"Human symptoms-disease network.","volume":"5","author":"X Zhou","year":"2014","journal-title":"Nat Commun."},{"key":"ref-53","doi-asserted-by":"publisher","first-page":"753-761","DOI":"10.1093\/aje\/kwx227","article-title":"Current Challenges and New Opportunities for Gene-Environment Interaction Studies of Complex Diseases.","volume":"186","author":"K McAllister","year":"2017","journal-title":"Am J Epidemiol."},{"key":"ref-54","doi-asserted-by":"publisher","first-page":"3956-3966","DOI":"10.1242\/jcs.080374","article-title":"Cell organization, growth, and neural and cardiac development require \u03b1II-spectrin.","volume":"124","author":"M Stankewich","year":"2011","journal-title":"J Cell Sci."},{"key":"ref-55","doi-asserted-by":"publisher","first-page":"926-932","DOI":"10.1086\/378159","article-title":"Slowed conduction and thin myelination of peripheral nerves associated with mutant rho Guanine-nucleotide exchange factor 10.","volume":"73","author":"K Verhoeven","year":"2003","journal-title":"Am J Hum Genet."},{"key":"ref-56","doi-asserted-by":"publisher","first-page":"e0161909","DOI":"10.1371\/journal.pone.0161909","article-title":"In Silico and Biochemical Characterization of Lysozyme-Like Proteins in the Rat.","volume":"11","author":"G Narmadha","year":"2016","journal-title":"PLoS One."},{"key":"ref-57","doi-asserted-by":"publisher","first-page":"1027-1041","DOI":"10.1093\/brain\/aws045","article-title":"KIAA1797\/FOCAD encodes a novel focal adhesion protein with tumour suppressor function in gliomas.","volume":"135","author":"A Brockschmidt","year":"2012","journal-title":"Brain."},{"key":"ref-58","doi-asserted-by":"publisher","first-page":"155-164","DOI":"10.1002\/path.4520","article-title":"Germline deletions in the tumour suppressor gene FOCAD are associated with polyposis and colorectal cancer development.","volume":"236","author":"R Weren","year":"2015","journal-title":"J Pathol."},{"key":"ref-59","doi-asserted-by":"publisher","first-page":"290-298","DOI":"10.1038\/ng.82","article-title":"MicroRNA Mirn140 modulates Pdgf signaling during palatogenesis.","volume":"40","author":"J Eberhart","year":"2008","journal-title":"Nat Genet."},{"key":"ref-60","doi-asserted-by":"publisher","first-page":"427-435","DOI":"10.1080\/15216540701510581","article-title":"Let's stick together: the role of the Fras1 and Frem proteins in epidermal adhesion.","volume":"59","author":"K Short","year":"2007","journal-title":"IUBMB Life."},{"key":"ref-61","doi-asserted-by":"publisher","first-page":"203-208","DOI":"10.1038\/ng1142","article-title":"Fraser syndrome and mouse blebbed phenotype caused by mutations in FRAS1\/Fras1 encoding a putative extracellular matrix protein.","volume":"34","author":"L McGregor","year":"2003","journal-title":"Nat Genet."},{"key":"ref-62","doi-asserted-by":"publisher","first-page":"3750-3756","DOI":"10.1128\/mcb.12.9.3750","article-title":"Isolation of Rsp-1, a Novel Cdna Capable of Suppressing V-Ras Transformation.","volume":"12","author":"M Cutler","year":"1992","journal-title":"Mol Cell Biol."},{"key":"ref-63","doi-asserted-by":"publisher","first-page":"907-916","DOI":"10.4161\/cbt.8.10.8132","article-title":"Characterization CSMD1 in a large set of primary lung, head and neck, breast and skin cancer tissues.","volume":"8","author":"C Ma","year":"2009","journal-title":"Cancer Biol Ther."},{"key":"ref-64","doi-asserted-by":"publisher","first-page":"555-563","DOI":"10.1007\/s10549-009-0500-4","article-title":"Loss of CSMD1 expression is associated with high tumour grade and poor survival in invasive ductal breast carcinoma.","volume":"121","author":"M Kamal","year":"2010","journal-title":"Breast Cancer Res Treat."},{"key":"ref-65","doi-asserted-by":"publisher","first-page":"1155-1162","DOI":"10.1016\/S0140-6736(02)11203-7","article-title":"Clinical importance of the cytochromes P450.","volume":"360","author":"D Nebert","year":"2002","journal-title":"Lancet."}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/8-960\/v2\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/8-960\/v2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/8-960\/v2\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,23]],"date-time":"2019-09-23T14:43:31Z","timestamp":1569249811000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/8-960\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,19]]},"references-count":65,"URL":"https:\/\/doi.org\/10.12688\/f1000research.19571.2","relation":{"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.21886.r51378","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.21886.r51378","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,19]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/8-960\/v2#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.21886.r51378, Evie Stergiakouli, School of Oral and Dental Sciences, University of Bristol, Bristol, UK, 26 Jul 2019, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/8-960\/v2#referee-response-51378","order":0,"name":"referee-response-51378","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.21459.r50328, Yongchu Pan, Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University (NMU), Nanjing, China, 25 Jul 2019, version 1, 1 approved, 1 approved with reservations","URL":"https:\/\/f1000research.com\/articles\/8-960\/v1#referee-response-50328","order":1,"name":"referee-response-50328","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This research was supported by the Bergen Medical Research Foundation [807191], by the Research Council of Norway (RCN) through its Centres of Excellence funding scheme [grant 262700], and by the Biobank Norway II from the RCN [245464]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Data associated with the article are available under the terms of the Creative Commons Zero \"No rights reserved\" data waiver (CC0 1.0 Public domain dedication).","order":0,"name":"copyright-info","label":"Copyright"}]}}