{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T00:53:57Z","timestamp":1792889637788,"version":"4.5.0"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2019,12,17]],"date-time":"2019-12-17T00:00:00Z","timestamp":1576540800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,12,17]],"date-time":"2019-12-17T00:00:00Z","timestamp":1576540800000},"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":["R01-DE016148"],"award-info":[{"award-number":["R01-DE016148"]}],"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":["R03-DE026469"],"award-info":[{"award-number":["R03-DE026469"]}],"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":["R01-DE016148"],"award-info":[{"award-number":["R01-DE016148"]}],"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":["R03-DE026469"],"award-info":[{"award-number":["R03-DE026469"]}],"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-DD000295"],"award-info":[{"award-number":["U01-DD000295"]}],"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":["R01-DE014581"],"award-info":[{"award-number":["R01-DE014581"]}],"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":["R01-DE011931"],"award-info":[{"award-number":["R01-DE011931"]}],"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":["R01-DE014667"],"award-info":[{"award-number":["R01-DE014667"]}],"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":["R00-DE025060"],"award-info":[{"award-number":["R00-DE025060"]}],"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":["R01-DE012472"],"award-info":[{"award-number":["R01-DE012472"]}],"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":["R21-DE016930"],"award-info":[{"award-number":["R21-DE016930"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Hum Genet"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Orofacial clefts (OFCs) are among the most prevalent craniofacial birth defects worldwide and create a significant public health burden. The majority of OFCs are non-syndromic, and the genetic etiology of non-syndromic OFCs is only partially determined. Here, we analyze whole genome sequence (WGS) data for association with risk of OFCs in European and Colombian families selected from a multicenter family-based OFC study. This is the first large-scale WGS study of OFC in parent\u2013offspring trios, and a part of the Gabriella Miller Kids First Pediatric Research Program created for the study of childhood cancers and structural birth defects. WGS provides deeper and more specific genetic data than using imputation on present-day single nucleotide polymorphic (SNP) marker panels. Genotypes of case\u2013parent trios at single nucleotide variants (SNV) and short insertions and deletions (indels) spanning the entire genome were called from their sequences using human GRCh38 genome assembly, and analyzed for association using the transmission disequilibrium test. Among genome-wide significant associations, we identified a new locus on chromosome 21 in Colombian families, not previously observed in other larger OFC samples of Latin American ancestry. This locus is situated within a region known to be expressed during craniofacial development. Based on deeper investigation of this locus, we concluded that it contributed risk for OFCs exclusively in the Colombians. This study reinforces the ancestry differences seen in the genetic etiology of OFCs, and underscores the need for larger samples when studying for OFCs and other birth defects in populations with diverse ancestry.<\/jats:p>","DOI":"10.1007\/s00439-019-02099-1","type":"journal-article","created":{"date-parts":[[2019,12,17]],"date-time":"2019-12-17T10:02:48Z","timestamp":1576576968000},"page":"215-226","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Whole genome sequencing of orofacial cleft trios from the Gabriella Miller Kids First Pediatric Research Consortium identifies a new locus on chromosome 21"],"prefix":"10.1007","volume":"139","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7117-9536","authenticated-orcid":false,"given":"Nandita","family":"Mukhopadhyay","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madison","family":"Bishop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Mortillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pankaj","family":"Chopra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline B.","family":"Hetmanski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret A.","family":"Taub","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina M.","family":"Moreno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luz Consuelo","family":"Valencia-Ramirez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Restrepo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George L.","family":"Wehby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline T.","family":"Hecht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic","family":"Deleyiannis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azeez","family":"Butali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth M.","family":"Weinberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terri H.","family":"Beaty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey C.","family":"Murray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth J.","family":"Leslie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanor","family":"Feingold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary L.","family":"Marazita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,12,17]]},"reference":[{"key":"2099_CR1","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1038\/ng.580","volume":"42","author":"TH Beaty","year":"2010","unstructured":"Beaty TH et al (2010) A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4. Nat Genet 42:525\u2013529. https:\/\/doi.org\/10.1038\/ng.580","journal-title":"Nat Genet"},{"key":"2099_CR2","doi-asserted-by":"publisher","first-page":"2800","DOI":"10.12688\/f1000research.9503.1","volume":"5","author":"TH Beaty","year":"2016","unstructured":"Beaty TH, Marazita ML, Leslie EJ (2016) Genetic factors influencing risk to orofacial clefts: today\u2019s challenges and tomorrow\u2019s opportunities. F1000Research 5:2800. https:\/\/doi.org\/10.12688\/f1000research.9503.1","journal-title":"F1000Research"},{"key":"2099_CR3","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1093\/aje\/kwi132","volume":"161","author":"C Bille","year":"2005","unstructured":"Bille C, Winther JF, Bautz A, Murray JC, Olsen J, Christensen K (2005) Cancer risk in persons with oral cleft\u2013a population-based study of 8093 cases. Am J Epidemiol 161:1047\u20131055. https:\/\/doi.org\/10.1093\/aje\/kwi132","journal-title":"Am J Epidemiol"},{"key":"2099_CR4","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1111\/j.1600-0722.2009.00680.x","volume":"117","author":"S Birnbaum","year":"2009","unstructured":"Birnbaum S et al (2009) IRF6 gene variants in Central European patients with non-syndromic cleft lip with or without cleft palate. Eur J Oral Sci 117:766\u2013769. https:\/\/doi.org\/10.1111\/j.1600-0722.2009.00680.x","journal-title":"Eur J Oral Sci"},{"key":"2099_CR5","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1086\/521987","volume":"81","author":"SR Browning","year":"2007","unstructured":"Browning SR, Browning BL (2007) Rapid and accurate haplotype phasing and missing-data inference for whole-genome association studies by use of localized haplotype clustering. Am J Hum Genet 81:1084\u20131097. https:\/\/doi.org\/10.1086\/521987","journal-title":"Am J Hum Genet"},{"key":"2099_CR6","doi-asserted-by":"publisher","first-page":"S178","DOI":"10.1097\/sap.0000000000001331","volume":"80","author":"AH Bui","year":"2018","unstructured":"Bui AH, Ayub A, Ahmed MK, Taioli E, Taub PJ (2018) Association between cleft lip and\/or cleft palate and family history of cancer: a case-control study. Ann Plast Surg 80:S178\u2013s181. https:\/\/doi.org\/10.1097\/sap.0000000000001331","journal-title":"Ann Plast Surg"},{"key":"2099_CR7","doi-asserted-by":"publisher","first-page":"D1005","DOI":"10.1093\/nar\/gky1120","volume":"47","author":"A Buniello","year":"2019","unstructured":"Buniello A et al (2019) The NHGRI-EBI GWAS Catalog of published genome-wide association studies, targeted arrays and summary statistics 2019. Nucleic Acids Res 47:D1005\u2013d1012. https:\/\/doi.org\/10.1093\/nar\/gky1120","journal-title":"Nucleic Acids Res"},{"key":"2099_CR8","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s13742-015-0047-8","volume":"4","author":"CC Chang","year":"2015","unstructured":"Chang CC, Chow CC, Tellier LC, Vattikuti S, Purcell SM, Lee JJ (2015) Second-generation PLINK: rising to the challenge of larger and richer datasets. GigaScience 4:7. https:\/\/doi.org\/10.1186\/s13742-015-0047-8","journal-title":"GigaScience"},{"key":"2099_CR9","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1038\/ng.806","volume":"43","author":"MA DePristo","year":"2011","unstructured":"DePristo MA et al (2011) A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat Genet 43:491\u2013498. https:\/\/doi.org\/10.1038\/ng.806","journal-title":"Nat Genet"},{"key":"2099_CR10","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1038\/nrg2933","volume":"12","author":"MJ Dixon","year":"2011","unstructured":"Dixon MJ, Marazita ML, Beaty TH, Murray JC (2011) Cleft lip and palate: understanding genetic and environmental influences. Nat Rev Genet 12:167\u2013178. https:\/\/doi.org\/10.1038\/nrg2933","journal-title":"Nat Rev Genet"},{"key":"2099_CR11","doi-asserted-by":"publisher","DOI":"10.1097\/ede.0b013e3182125f9c","author":"MH Gouveia","year":"2019","unstructured":"Gouveia MH et al (2019) Origins, admixture dynamics and homogenization of the African gene pool in the Americas. bioRxiv. https:\/\/doi.org\/10.1097\/ede.0b013e3182125f9c","journal-title":"bioRxiv"},{"key":"2099_CR12","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1101\/652701","volume":"22","author":"D Grosen","year":"2011","unstructured":"Grosen D et al (2011) Risk of oral clefts in twins. Epidemiology (Cambridge, Mass) 22:313\u2013319. https:\/\/doi.org\/10.1101\/652701","journal-title":"Epidemiology (Cambridge, Mass)"},{"key":"2099_CR13","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1080\/15384101.2015.1120928","volume":"15","author":"DJ Hazelett","year":"2016","unstructured":"Hazelett DJ et al (2016) Reducing GWAS complexity. Cell Cycle (Georgetown, Tex) 15:22\u201324. https:\/\/doi.org\/10.1080\/15384101.2015.1120928","journal-title":"Cell Cycle (Georgetown, Tex)"},{"key":"2099_CR14","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.ajhg.2013.11.021","volume":"94","author":"Z He","year":"2014","unstructured":"He Z et al (2014) Rare-variant extensions of the transmission disequilibrium test: application to autism exome sequence data. Am J Hum Genet 94:33\u201346. https:\/\/doi.org\/10.1016\/j.ajhg.2013.11.021","journal-title":"Am J Hum Genet"},{"key":"2099_CR15","doi-asserted-by":"publisher","DOI":"10.1101\/531210","author":"KJ Karczewski","year":"2019","unstructured":"Karczewski KJ et al (2019) Variation across 141,456 human exomes and genomes reveals the spectrum of loss-of-function intolerance across human protein-coding genes. bioRxiv. https:\/\/doi.org\/10.1101\/531210","journal-title":"bioRxiv"},{"key":"2099_CR16","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/s13059-018-1387-3","volume":"19","author":"AV Kotlar","year":"2018","unstructured":"Kotlar AV, Trevino CE, Zwick ME, Cutler DJ, Wingo TS (2018) Bystro: rapid online variant annotation and natural-language filtering at whole-genome scale. Genome Biol 19:14. https:\/\/doi.org\/10.1186\/s13059-018-1387-3","journal-title":"Genome Biol"},{"key":"2099_CR17","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/s0065-2660(07)00410-5","volume":"60","author":"NM Laird","year":"2008","unstructured":"Laird NM, Lange C (2008) Family-based methods for linkage and association analysis. Adv Genet 60:219\u2013252. https:\/\/doi.org\/10.1016\/s0065-2660(07)00410-5","journal-title":"Adv Genet"},{"key":"2099_CR18","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/j.ajhg.2015.01.004","volume":"96","author":"EJ Leslie","year":"2015","unstructured":"Leslie EJ et al (2015) Identification of functional variants for cleft lip with or without cleft palate in or near PAX7, FGFR2, and NOG by targeted sequencing of GWAS loci. Am J Hum Genet 96:397\u2013411. https:\/\/doi.org\/10.1016\/j.ajhg.2015.01.004","journal-title":"Am J Hum Genet"},{"key":"2099_CR19","doi-asserted-by":"publisher","first-page":"2862","DOI":"10.1093\/hmg\/ddw104","volume":"25","author":"EJ Leslie","year":"2016","unstructured":"Leslie EJ et al (2016) A multi-ethnic genome-wide association study identifies novel loci for non-syndromic cleft lip with or without cleft palate on 2p24.2, 17q23 and 19q13. Hum Mol Genet 25:2862\u20132872. https:\/\/doi.org\/10.1093\/hmg\/ddw104","journal-title":"Hum Mol Genet"},{"key":"2099_CR20","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1038\/ng.2360","volume":"44","author":"KU Ludwig","year":"2012","unstructured":"Ludwig KU et al (2012) Genome-wide meta-analyses of nonsyndromic cleft lip with or without cleft palate identify six new risk loci. Nat Genet 44:968\u2013971. https:\/\/doi.org\/10.1038\/ng.2360","journal-title":"Nat Genet"},{"key":"2099_CR21","doi-asserted-by":"publisher","first-page":"2867","DOI":"10.1093\/bioinformatics\/btq559","volume":"26","author":"A Manichaikul","year":"2010","unstructured":"Manichaikul A, Mychaleckyj JC, Rich SS, Daly K, Sale M, Chen WM (2010) Robust relationship inference in genome-wide association studies. Bioinformatics (Oxford, England) 26:2867\u20132873. https:\/\/doi.org\/10.1093\/bioinformatics\/btq559","journal-title":"Bioinformatics (Oxford, England)"},{"key":"2099_CR22","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1038\/nature08494","volume":"461","author":"TA Manolio","year":"2009","unstructured":"Manolio TA et al (2009) Finding the missing heritability of complex diseases. Nature 461:747\u2013753. https:\/\/doi.org\/10.1038\/nature08494","journal-title":"Nature"},{"key":"2099_CR23","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1101\/gr.107524.110","volume":"20","author":"A McKenna","year":"2010","unstructured":"McKenna A et al (2010) The genome analysis toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res 20:1297\u20131303. https:\/\/doi.org\/10.1101\/gr.107524.110","journal-title":"Genome Res"},{"key":"2099_CR24","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1186\/s13059-016-0974-4","volume":"17","author":"W McLaren","year":"2016","unstructured":"McLaren W et al (2016) The ensembl variant effect predictor. Genome Biol 17:122. https:\/\/doi.org\/10.1186\/s13059-016-0974-4","journal-title":"Genome Biol"},{"key":"2099_CR25","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1002\/gepi.21633","volume":"36","author":"T Murray","year":"2012","unstructured":"Murray T et al (2012) Examining markers in 8q24 to explain differences in evidence for association with cleft lip with\/without cleft palate between Asians and Europeans. Genet Epidemiol 36:392\u2013399. https:\/\/doi.org\/10.1002\/gepi.21633","journal-title":"Genet Epidemiol"},{"key":"2099_CR26","doi-asserted-by":"publisher","first-page":"1758","DOI":"10.1016\/j.jcms.2018.07.004","volume":"46","author":"A Naros","year":"2018","unstructured":"Naros A, Brocks A, Kluba S, Reinert S, Krimmel M (2018) Health-related quality of life in cleft lip and\/or palate patients\u2014a cross-sectional study from preschool age until adolescence. J Craniomaxillofac Surg 46:1758\u20131763. https:\/\/doi.org\/10.1016\/j.jcms.2018.07.004","journal-title":"J Craniomaxillofac Surg"},{"issue":"1","key":"2099_CR27","doi-asserted-by":"crossref","first-page":"2","DOI":"10.31532\/OralHealthDentStud.2.1.002","volume":"2","author":"N Nidey","year":"2019","unstructured":"Nidey N, Wehby G (2019) Barriers to health care for children with orofacial clefts: a systematic literature review and recommendations for research priorities. Oral Health Dent Stud 2(1):2","journal-title":"Oral Health Dent Stud"},{"key":"2099_CR28","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1111\/cch.12276","volume":"42","author":"N Nidey","year":"2016","unstructured":"Nidey N, Moreno Uribe LM, Marazita MM, Wehby GL (2016) Psychosocial well-being of parents of children with oral clefts. Child Care Health Dev 42:42\u201350. https:\/\/doi.org\/10.1111\/cch.12276","journal-title":"Child Care Health Dev"},{"key":"2099_CR29","doi-asserted-by":"publisher","first-page":"2840","DOI":"10.1093\/bioinformatics\/btu383","volume":"30","author":"H Poon","year":"2014","unstructured":"Poon H, Quirk C, DeZiel C, Heckerman D (2014) Literome: pubmed-scale genomic knowledge base in the cloud. Bioinformatics (Oxford, England) 30:2840\u20132842. https:\/\/doi.org\/10.1093\/bioinformatics\/btu383","journal-title":"Bioinformatics (Oxford, England)"},{"key":"2099_CR30","unstructured":"Purcell S, Chang C (2019) PLINK version 1.9, cited October 2019, available at URL: http:\/\/www.cog-genomics.org\/plink\/1.9\/"},{"key":"2099_CR31","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1597\/10-178","volume":"49","author":"F Rahimov","year":"2012","unstructured":"Rahimov F, Jugessur A, Murray JC (2012) Genetics of nonsyndromic orofacial cleft. Cleft Palate-craniofac J 49:73\u201391. https:\/\/doi.org\/10.1597\/10-178","journal-title":"Cleft Palate-craniofac J"},{"key":"2099_CR32","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1002\/(sici)1098-2272(1996)13:5<423::Aid-gepi1>3.0.Co;2-3","volume":"13","author":"DJ Schaid","year":"1996","unstructured":"Schaid DJ (1996) General score tests for associations of genetic markers with disease using cases and their parents. Genet Epidemiol 13:423\u2013449. https:\/\/doi.org\/10.1002\/(sici)1098-2272(1996)13:5%3c423:Aid-gepi1%3e3.0.Co;2-3","journal-title":"Genet Epidemiol"},{"key":"2099_CR33","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1111\/j.1541-0420.2011.01713.x","volume":"68","author":"H Schwender","year":"2012","unstructured":"Schwender H, Taub MA, Beaty TH, Marazita ML, Ruczinski I (2012) Rapid testing of SNPs and gene-environment interactions in case-parent trio data based on exact analytic parameter estimation. Biometrics 68:766\u2013773. https:\/\/doi.org\/10.1111\/j.1541-0420.2011.01713.x","journal-title":"Biometrics"},{"key":"2099_CR34","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1002\/gepi.21836","volume":"38","author":"H Schwender","year":"2014","unstructured":"Schwender H et al (2014) Detecting disease variants in case-parent trio studies using the bioconductor software package trio. Genet Epidemiol 38:516\u2013522. https:\/\/doi.org\/10.1002\/gepi.21836","journal-title":"Genet Epidemiol"},{"key":"2099_CR35","first-page":"559","volume":"54","author":"RS Spielman","year":"1994","unstructured":"Spielman RS, McGinnis RE, Ewens WJ (1994) The transmission\/disequilibrium test detects cosegregation and linkage. Am J Hum Genet 54:559\u2013560 (author reply 560-553)","journal-title":"Am J Hum Genet"},{"key":"2099_CR36","doi-asserted-by":"publisher","first-page":"958","DOI":"10.3109\/07357907.2010.483510","volume":"28","author":"E Taioli","year":"2010","unstructured":"Taioli E, Ragin C, Robertson L, Linkov F, Thurman NE, Vieira AR (2010) Cleft lip and palate in family members of cancer survivors. Cancer Invest 28:958\u2013962. https:\/\/doi.org\/10.3109\/07357907.2010.483510","journal-title":"Cancer Invest"},{"key":"2099_CR37","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/s13072-015-0050-4","volume":"8","author":"YG Tak","year":"2015","unstructured":"Tak YG, Farnham PJ (2015) Making sense of GWAS: using epigenomics and genome engineering to understand the functional relevance of SNPs in non-coding regions of the human genome. Epigenet Chromatin 8:57. https:\/\/doi.org\/10.1186\/s13072-015-0050-4","journal-title":"Epigenet Chromatin"},{"key":"2099_CR38","doi-asserted-by":"publisher","first-page":"11.10.11","DOI":"10.1002\/0471250953.bi1110s43","volume":"43","author":"GA Van der Auwera","year":"2013","unstructured":"Van der Auwera GA et al (2013) From FastQ data to high confidence variant calls: the genome analysis toolkit best practices pipeline. Curr Protoc Bioinform 43:11.10.11\u201311.10.33. https:\/\/doi.org\/10.1002\/0471250953.bi1110s43","journal-title":"Curr Protoc Bioinform"},{"key":"2099_CR39","doi-asserted-by":"publisher","DOI":"10.1101\/588020","author":"P Wainschtein","year":"2019","unstructured":"Wainschtein P et al (2019) Recovery of trait heritability from whole genome sequence data. bioRxi. https:\/\/doi.org\/10.1101\/588020","journal-title":"bioRxi"},{"key":"2099_CR40","doi-asserted-by":"publisher","first-page":"D877","DOI":"10.1093\/nar\/gkv1340","volume":"44","author":"LD Ward","year":"2016","unstructured":"Ward LD, Kellis M (2016) HaploReg v4: systematic mining of putative causal variants, cell types, regulators and target genes for human complex traits and disease. Nucleic Acids Res 44:D877\u2013881. https:\/\/doi.org\/10.1093\/nar\/gkv1340","journal-title":"Nucleic Acids Res"},{"key":"2099_CR41","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1111\/j.1601-0825.2009.01588.x","volume":"16","author":"GL Wehby","year":"2010","unstructured":"Wehby GL, Cassell CH (2010) The impact of orofacial clefts on quality of life and healthcare use and costs. Oral Dis 16:3\u201310. https:\/\/doi.org\/10.1111\/j.1601-0825.2009.01588.x","journal-title":"Oral Dis"},{"key":"2099_CR42","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1016\/j.mod.2007.06.007","volume":"124","author":"IC Welsh","year":"2007","unstructured":"Welsh IC, Hagge-Greenberg A, O\u2019Brien TP (2007) A dosage-dependent role for Spry2 in growth and patterning during palate development. Mech Dev 124:746\u2013761. https:\/\/doi.org\/10.1016\/j.mod.2007.06.007","journal-title":"Mech Dev"},{"key":"2099_CR43","doi-asserted-by":"publisher","first-page":"1581","DOI":"10.1016\/j.celrep.2018.03.129","volume":"23","author":"A Wilderman","year":"2018","unstructured":"Wilderman A, VanOudenhove J, Kron J, Noonan JP, Cotney J (2018) High-resolution epigenomic atlas of human embryonic craniofacial development. Cell Rep 23:1581\u20131597. https:\/\/doi.org\/10.1016\/j.celrep.2018.03.129","journal-title":"Cell Rep"},{"key":"2099_CR44","doi-asserted-by":"publisher","first-page":"1325","DOI":"10.1177\/1535370217713750","volume":"242","author":"Y Zhu","year":"2017","unstructured":"Zhu Y, Tazearslan C, Suh Y (2017) Challenges and progress in interpretation of non-coding genetic variants associated with human disease. Exp Biol Med (Maywood, NJ) 242:1325\u20131334. https:\/\/doi.org\/10.1177\/1535370217713750","journal-title":"Exp Biol Med (Maywood, NJ)"}],"container-title":["Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00439-019-02099-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00439-019-02099-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00439-019-02099-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T14:14:35Z","timestamp":1665238475000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00439-019-02099-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,17]]},"references-count":44,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,2]]}},"alternative-id":["2099"],"URL":"https:\/\/doi.org\/10.1007\/s00439-019-02099-1","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/743526","asserted-by":"object"}]},"ISSN":["0340-6717","1432-1203"],"issn-type":[{"value":"0340-6717","type":"print"},{"value":"1432-1203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,17]]},"assertion":[{"value":"26 September 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 December 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 December 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors have no conflict of interest to declare.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}