{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"contact_person":["STYLIANOS  ANTONARAKIS"],"full_dataset_link":["https://ega-archive.org/dacs/EGAC01000000023"],"host":["EGA"],"description":["EGA DAC EGAC01000000023"],"repository":["EGA"],"email":["Stylianos.Antonarakis@unige.ch"],"pubmed_abstract":["Congenital heart defect (CHD) occurs in 40% of Down syndrome (DS) cases. While carrying three copies of chromosome 21 increases the risk for CHD, trisomy 21 itself is not sufficient to cause CHD. Thus, additional genetic variation and/or environmental factors could contribute to the CHD risk. Here we report genomic variations that in concert with trisomy 21, determine the risk for CHD in DS. This case-control GWAS includes 187 DS with CHD (AVSD = 69, ASD = 53, VSD = 65) as cases, and 151 DS without CHD as controls. Chromosome 21-specific association studies revealed rs2832616 and rs1943950 as CHD risk alleles (adjusted genotypic P-values <0.05). These signals were confirmed in a replication cohort of 92 DS-CHD cases and 80 DS-without CHD (nominal P-value 0.0022). Furthermore, CNV analyses using a customized chromosome 21 aCGH of 135K probes in 55 DS-AVSD and 53 DS-without CHD revealed three CNV regions associated with AVSD risk (FDR ≤ 0.05). Two of these regions that are located within the previously identified CHD region on chromosome 21 were further confirmed in a replication study of 49 DS-AVSD and 45 DS- without CHD (FDR ≤ 0.05). One of these CNVs maps near the RIPK4 gene, and the second includes the ZBTB21 (previously ZNF295) gene, highlighting the potential role of these genes in the pathogenesis of CHD in DS. We propose that the genetic architecture of the CHD risk of DS is complex and includes trisomy 21, and SNP and CNV variations in chromosome 21. In addition, a yet-unidentified genetic variation in the rest of the genome may contribute to this complex genetic architecture."],"pubmed_title":["The complex SNP and CNV genetic architecture of the increased risk of congenital heart defects in Down syndrome."],"pubmed_authors":["Sailani M Reza MR, Makrythanasis Periklis P, Valsesia Armand A, Santoni Federico A FA, Deutsch Samuel S, Popadin Konstantin K, Borel Christelle C, Migliavacca Eugenia E, Sharp Andrew J AJ, Duriaux Sail Genevieve G, Falconnet Emilie E, Rabionet Kelly K, Serra-Juhé Clara C, Vicari Stefano S, Laux Daniela D, Grattau Yann Y, Dembour Guy G, Megarbane Andre A, Touraine Renaud R, Stora Samantha S, Kitsiou Sofia S, Fryssira Helena H, Chatzisevastou-Loukidou Chariklia C, Kanavakis Emmanouel E, Merla Giuseppe G, Bonnet Damien D, Pérez-Jurado Luis A LA, Estivill Xavier X, Delabar Jean M JM, Antonarakis Stylianos E SE"],"name_synonyms":["XX, fbwd4, XY, Trisomy 21 NOS, 47, l(2)04454, DmelCG1772, dac, CIB1, G Trisomy, Trisomy 21, Down Syndrome, Down's Syndrome, Complete trisomy 21 syndrome, p21[dacapo], dactylin, E130112M23Rik, cdi4, Down's syndrome NOS (disorder), Complete trisomy 21 syndrome (disorder), +21, dactylyn, p21, CG1772, FBWD4, Down's, Cdi4, CDI4, p27, trisomy 21 syndrome, Down's syndrome - trisomy 21, Trisomy 21 Syndrome, Partial Trisomy 21 Down Syndrome, Down's syndrome NOS, shsf3, Trisomy G, shfm3, Decapo., complete trisomy 21 syndrome, E(Sev-CycE)2B, Fbw4, Mitotic Nondisjunction, FBW4, Mongolism, Down, Dach, CDKN2B, SHFM3, trisomy 21, Dac, DAC, p27[Dap], Meiotic Nondisjunction, Down syndrome, dacapo/cyclin-dependent kinase interactor 4, AI182278, Syndrome, Dap, CES5A1, T21 - Trisomy 21, P15, fbw4, SHSF3, Partial Trisomy 21, Downs Syndrome"],"pubmed_title_synonyms":["Heart, XX, XY, Congenital Heart Defect, Trisomy 21 NOS, 47, cg11478, Disease, Malformation Of Hearts, Abnormally shaped heart, G Trisomy, Abnormality, Trisomy 21, Down Syndrome, familial, defect, Congenital heart defect, Down's Syndrome, Complete trisomy 21 syndrome, CG30327, Heart defect, CG11478, Congenital Heart Disease, Congenital, Cardiac abnormality, abnormalities, Down's syndrome NOS (disorder), Complete trisomy 21 syndrome (disorder), +21, congenital, CG6393, heart, Heart Disease, Congenital heart defects, Down's, Congenital Heart Defects, defects, increase in risk, malformation Of, trisomy 21 syndrome, Abnormality of the heart, Dmel_CG6393, DmelCG42257, Congenital Heart Diseases, Abnormality of cardiac morphology, Malformation Of, congenital heart, heart-congenital defect, Trisomy 21 Syndrome, heart abnormalities, Partial Trisomy 21 Down Syndrome, Down's syndrome NOS, Cardiac anomaly, Down's syndrome - trisomy 21., Defects, Congenital Heart, Trisomy G, complete trisomy 21 syndrome, Cardiac anomalies, Heart Abnormalities, Defect, Mitotic Nondisjunction, Heart Abnormality, Mongolism, Heart Defect, genetic, Down, heart abnormality, Malformation Of Heart, trisomy 21, Meiotic Nondisjunction, Down syndrome, 65K, heart defect, Syndrome, CG42257, Dmel_CG30327, snp, inherited genetic, T21 - Trisomy 21, constitutitional genetic, hereditary, Partial Trisomy 21, Downs Syndrome"],"pubmed_abstract_synonyms":["Heart, TAPETUM 1, Trisomy 21 NOS, ZNF295, Malformation Of Hearts, CDH, Materials, Abnormally shaped heart, \"Congenital heart anomaly NOS (disorder)\" EXACT [SNOMEDCT_2005_07_31:204413006], positive regulation by symbiont of host non-apoptotic programmed cell death, Progress Reports, \"Heart Malformation\" EXACT [NCI2004_11_17:C34666], CG30327, PPS2, prevention, Intraventricular Septal, Relative, CG11478, abnormalities, Roles, congenital, Summary Report, Associations, Znf295, Heart Disease, atrioventricular septal defect, Concepts, pathogenesis, Congenital Heart Defects, prevention and control, Summary Reports, hereditary., ANKK2, \"heart defect\" EXACT [CSP2005:0724-8315], DmelCG42257, Congenital Heart Diseases, heart-congenital defect, reference sample, stimulation by symbiont of host programmed cell death, Progress Report, Genomes, Cardiac anomaly, Rests, Defects, ASD, Defect, genetic, preventive measures, Progress, heart abnormality, geographical area, trisomy 21, Field Reports, g, DIK, Meiotic Nondisjunction, \"Congenital Heart Defects\" EXACT [MTH:NOCODE], Role Concepts, megakaryoblastic, Allele, asd, s, \"Heart-congenital defect\" EXACT [SNOMEDCT_2005_07_31:156911006], Ventricular Septal, RIP4, Chd, CHD, 47, preventive therapy, DIk, ventricular, Trisomy 21, familial, Down's Syndrome, common AV canal, Maps, Diversities, 3.1.6.-, Septal Defects, ANKRD3, chd, heart septal defects, Ventricular Septal Defect, Congenital, Cardiac abnormality, Down's syndrome NOS (disorder), Role Concept, Investigative Report, XBR, CG6393, Relative Risks, Role, modulation by symbiont of host system process, Genetic Materials, Genetic Material, \"Congenital heart anomaly NOS\" EXACT [SNOMEDCT_2005_07_31:268318000], Dmel_CG6393, Abnormality of cardiac morphology, AI747421, positional polypeptide feature, Trisomy 21 Syndrome, Risk, mKIAA1227, Down's syndrome NOS, Autistic behaviors, Zfp295, Field, INSDC_feature:gene, Cardiac anomalies, Intraventricular Septal Defects, whole genome, Genetic Diversity, Mitotic Nondisjunction, X-chordin, Down, Report, Ankrd3, Material, activation by symbiont of host programmed cell death, atrioventricular canal defect, Cistron, inherited genetic, Partial Trisomy 21, Gruppe, XX, AA407358, XY, ALCOHOL DEHYDROGENASE, Allelomorphs, Ventricular, ventricular septal defects, NKRD3, G Trisomy, region or site annotation, regulation by symbiont of host system process, Abnormality, defect, Gene, Heart defect, \"Congenital heart anomaly NOS\" EXACT [SNOMEDCT_2005_07_31:204405005], Congenital Heart Disease, Gus, Gur, Gut, Investigative, TAPETUM1, induction by organism of non-apoptotic programmed cell death in other organism during symbiotic interaction, 5430437K12Rik, Congenital heart defects, Down's, NRSF, Carrying, defects, Chromosome 21, trisomy 21 syndrome, Down's syndrome - trisomy 21, Abnormality of the heart, study, positional, endocardial cushion defect, Diversity, Genetic, AVCD, congenital heart, Partial Trisomy 21 Down Syndrome, Down syndrome chromosome region, \"Congenital anomaly of heart\" EXACT [SNOMEDCT_2005_07_31:13213009], Congenital Heart, of Down syndrome, \"Congenital anomaly of heart NOS\" EXACT [MTHICD9_2006:746.9], causes, AVSD, Atrial septal defect, Heart Abnormality, Mongolism, Allelomorph, 1.1.99.1, TA1, Malformation Of Heart, ECD, grupos, Down syndrome, 65K, heart defect, Syndrome, causality, CG42257, Dmel_CG30327, transient myeloproliferative disorder of Down syndrome, Ventricular Septal Defects, snp, \"Heart-congenital defect\" EXACT [SNOMEDCT_2005_07_31:268315002], Investigative Reports, constitutitional genetic, Variation, Controlled, Genetic Variations, leukemia, Congenital Heart Defect, Intraventricular Septal Defect, Disease, Controlling, cg11478, coronary arteriosclerosis, \"Unspecified congenital anomaly of heart\" EXACT [ICD9CM_2006:746.9], activation by organism of non-apoptotic programmed cell death in other organism, Variations, grupo, hemolysin activity, Autistic behaviours, AI552420, Down Syndrome, Congenital heart defect, 2610008J04Rik, Septal Defect, 2310069J12Rik, common atrioventricular canal, TelN, Complete trisomy 21 syndrome, Cistrons, B430213I24Rik, AV septal defect, group, Concept, Complete trisomy 21 syndrome (disorder), +21, heart, Research Reports, Genetic Diversities, Autism spectrum disorders, sequence, PKK, malformation Of, Relative Risk, \"Congenital heart anomaly NOS\" EXACT [SNOMEDCT_2005_07_31:156926008], Malformation Of, heart abnormalities, prophylaxis, Trisomy G, Risks, Gus-u, Rest, Gus-t, complete trisomy 21 syndrome, Gus-s, Gus-r, Heart Abnormalities, Heart Defect, primary structure of sequence macromolecule, Reports, control, Down syndrome critical region, Autism spectrum disorder, interatrial communication, ResT, T21 - Trisomy 21, Intraventricular, Summary, hereditary, groupe, Downs Syndrome, Field Report"],"additional_accession":[]},"is_claimable":false,"name":"Down syndrome Data Access Committee (DS-DAC)","description":"Data Access Committee EGAC01000000023","dates":{"output":"2025-1-9"},"accession":"EGAC01000000023","cross_references":{"TAXONOMY":["9606"],"pubmed":["23783273"],"EGA":["EGAS00000000129","EGAD00010000464","EGAD00010000466"]}}