{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"technology_type":["Illumina HiSeq 2000, Illumina HiSeq 2000 (ILLUMINA)"],"study_type":["Whole Genome Sequencing"],"full_dataset_link":["https://ega-archive.org/studies/EGAS00001000090"],"host":["EGA"],"description":["EGA study EGAS00001000090"],"dataset_title":["UK10K_COHORT_ALSPAC REL-2012-06-02: Phenotype data","UK10K_COHORT_ALSPAC REL-2011-12-01","UK10K_COHORT_ALSPAC REL-2012-06-02"],"category":["restricted"],"repository":["EGA"],"pubmed_abstract":["Genome-wide association studies (GWAS) have provided strong evidence for inherited predisposition to childhood acute lymphoblastic leukaemia (ALL) identifying a number of risk loci. We have previously shown common SNPs at 9p21.3 influence ALL risk. These SNP associations are generally not themselves candidates for causality, but simply act as markers for functional variants. By means of imputation of GWAS data and subsequent validation SNP genotyping totalling 2,177 ALL cases and 8,240 controls, we have shown that the 9p21.3 association can be ascribed to the rare high-impact CDKN2A p.Ala148Thr variant (rs3731249; Odds ratio = 2.42, P = 3.45 × 10(-19)). The association between rs3731249 genotype and risk was not specific to particular subtype of B-cell ALL. The rs3731249 variant is associated with predominant nuclear localisation of the CDKN2A transcript suggesting the functional effect of p.Ala148Thr on ALL risk may be through compromised ability to inhibit cyclin D within the cytoplasm.","So far six susceptibility loci for renal cell carcinoma (RCC) have been discovered by genome-wide association studies (GWAS). To identify additional RCC common risk loci, we performed a meta-analysis of published GWAS (totalling 2,215 cases and 8,566 controls of Western-European background) with imputation using 1000 Genomes Project and UK10K Project data as reference panels and followed up the most significant association signals [22 single nucleotide polymorphisms (SNPs) and 3 indels in eight genomic regions] in 383 cases and 2,189 controls from The Cancer Genome Atlas (TCGA). A combined analysis identified a promising susceptibility locus mapping to 1q24.1 marked by the imputed SNP rs3845536 (Pcombined =2.30x10-8). Specifically, the signal maps to intron 4 of the ALDH9A1 gene (aldehyde dehydrogenase 9 family, member A1). We further evaluated this potential signal in 2,461 cases and 5,081 controls from the International Agency for Research on Cancer (IARC) GWAS of RCC cases and controls from multiple European regions. In contrast to earlier findings no association was shown in the IARC series (P=0.94; Pcombined =2.73x10-5). While variation at 1q24.1 represents a potential risk locus for RCC, future replication analyses are required to substantiate our observation.","Previous genome-wide association studies (GWASs) have shown that common genetic variation contributes to the heritable risk of glioma. To identify new glioma susceptibility loci, we conducted a meta-analysis of four GWAS (totalling 4,147 cases and 7,435 controls), with imputation using 1000 Genomes and UK10K Project data as reference. After genotyping an additional 1,490 cases and 1,723 controls we identify new risk loci for glioblastoma (GBM) at 12q23.33 (rs3851634, near POLR3B, P=3.02 × 10(-9)) and non-GBM at 10q25.2 (rs11196067, near VTI1A, P=4.32 × 10(-8)), 11q23.2 (rs648044, near ZBTB16, P=6.26 × 10(-11)), 12q21.2 (rs12230172, P=7.53 × 10(-11)) and 15q24.2 (rs1801591, near ETFA, P=5.71 × 10(-9)). Our findings provide further insights into the genetic basis of the different glioma subtypes.","Isolated populations can empower the identification of rare variation associated with complex traits through next generation association studies, but the generalizability of such findings remains unknown. Here we genotype 1,267 individuals from a Greek population isolate on the Illumina HumanExome Beadchip, in search of functional coding variants associated with lipids traits. We find genome-wide significant evidence for association between R19X, a functional variant in APOC3, with increased high-density lipoprotein and decreased triglycerides levels. Approximately 3.8% of individuals are heterozygous for this cardioprotective variant, which was previously thought to be private to the Amish founder population. R19X is rare (<0.05% frequency) in outbred European populations. The increased frequency of R19X enables discovery of this lipid traits signal at genome-wide significance in a small sample size. This work exemplifies the value of isolated populations in successfully detecting transferable rare variant associations of high medical relevance."],"pubmed_title":["Genome-wide association study identifies multiple susceptibility loci for glioma.","Common variation at 1q24.1 (ALDH9A1) is a potential risk factor for renal cancer.","A rare functional cardioprotective APOC3 variant has risen in frequency in distinct population isolates.","The 9p21.3 risk of childhood acute lymphoblastic leukaemia is explained by a rare high-impact variant in CDKN2A."],"pubmed_authors":["Henrion Marc Y R MY, Purdue Mark P MP, Scelo Ghislaine G, Broderick Peter P, Frampton Matthew M, Ritchie Alastair A, Meade Angela A, Li Peng P, McKay James J, Johansson Mattias M, Lathrop Mark M, Larkin James J, Rothman Nathaniel N, Wang Zhaoming Z, Chow Wong-Ho WH, Stevens Victoria L VL, Diver W Ryan WR, Albanes Demetrius D, Virtamo Jarmo J, Brennan Paul P, Eisen Timothy T, Chanock Stephen S, Houlston Richard S RS","Tachmazidou Ioanna I, Dedoussis George G, Southam Lorraine L, Farmaki Aliki-Eleni AE, Ritchie Graham R S GR, Xifara Dionysia K DK, Matchan Angela A, Hatzikotoulas Konstantinos K, Rayner Nigel W NW, Chen Yuan Y, Pollin Toni I TI, O'Connell Jeffrey R JR, Yerges-Armstrong Laura M LM, Kiagiadaki Chrysoula C, Panoutsopoulou Kalliope K, Schwartzentruber Jeremy J, Moutsianas Loukas L, Tsafantakis Emmanouil E, Tyler-Smith Chris C, McVean Gil G, Xue Yali Y, Zeggini Eleftheria E","Vijayakrishnan Jayaram J, Henrion Marc M, Moorman Anthony V AV, Fiege Bettina B, Kumar Rajiv R, da Silva Filho Miguel Inacio MI, Holroyd Amy A, Koehler Rolf R, Thomsen Hauke H, Irving Julie A JA, Allan James M JM, Lightfoot Tracy T, Roman Eve E, Kinsey Sally E SE, Sheridan Eamonn E, Thompson Pamela D PD, Hoffmann Per P, Nöthen Markus M MM, Mühleisen Thomas W TW, Eisele Lewin L, Bartram Claus R CR, Schrappe Martin M, Greaves Mel M, Hemminki Kari K, Harrison Christine J CJ, Stanulla Martin M, Houlston Richard S RS","Kinnersley Ben B, Labussière Marianne M, Holroyd Amy A, Di Stefano Anna-Luisa AL, Broderick Peter P, Vijayakrishnan Jayaram J, Mokhtari Karima K, Delattre Jean-Yves JY, Gousias Konstantinos K, Schramm Johannes J, Schoemaker Minouk J MJ, Fleming Sarah J SJ, Herms Stefan S, Heilmann Stefanie S, Schreiber Stefan S, Wichmann Heinz-Erich HE, Nöthen Markus M MM, Swerdlow Anthony A, Lathrop Mark M, Simon Matthias M, Bondy Melissa M, Sanson Marc M, Houlston Richard S RS"],"description_synonyms":["Networks, setulae, Disorders, Kinship, single-organism developmental process, Activity, Laboratory, acetylglucosaminyltransferase-like protein, PNT-P1, Blood, DmelCG17077, postnatal development, Mbp1, Nail, EY3-1, growth and development, yolk stalk, Pregnant Women, Pnt, TALL-2, Adiposis, Disorders Usually Diagnosed in Infancy, Milk, Status, Hair, Obese, Techniques, unspecified, sampling, png, diseases, Method, hindlimb claw, Life Cycle, diseases and disorders, AW048865, Cow's, Umbilical Cords, D-ets-2, 3520, Research Activity, myd, Laboratory Research, Family Life Cycle, Pnt-P1, Priorities, average, me75, human disease, Fetal Hairs, Kinship Network, like-acetylglucosaminyltransferase, Genomes, pre-mortem, TRDL-1, vibrissa, Mbp-1, Information Retrieval System, procedures, D17Mit170, T1, genetic, Methodological Studies, Fetal, urinary aspects, Conserved, sample, birth cord, Homo sapiens disease, Ancillary Information Systems, Mental Disorders, Fingernails, Research Priority, Family Life Cycles, Toenails, Information Retrieval, protein-coding, close to, cord blood, notes, Child Mental Disorder, Child Mental, claw of toe, wide/broad, gyltl1b-b, Step Parents, frequency, SSP29, familial, Pregnant Woman, D-Ets-2, Research Priorities, Hairs, ets94F, 0123/09, Normalcy, Procedure, Umbilical, Tl3, Tl2, Stepparent, fetal blood, funiculus umbilicalis, Umbilical Cord Bloods, Parenthood, Perinatal, MDDGA6, mKIAA0609, Diseases, Obesity [Ambiguous], Obese (finding), Step-Parents, OBESITY, Neurodevelopmental Disorders Usually Diagnosed in Infancy, materials, Individual, KIAA0609, Filiation, connecting stalk, acetylglucosaminyltransferase-like 1A, Research and Development, fg, Parent, pntP2, whisker, gyltl1b, Child Mental Disorders, Pointed-P1, Parental Age, Information System, 2310026N09Rik, Ets94F, mdc1d, Exomes, Parental Ages, claw of pes, Adiposity, whole genome, Methodological, umbilical cord blood, surveillance, Methodological Study, Children, LARGE_HUMAN, morbidity, Age, Activities, ptd, Phenotypes, Life Cycles, disease, Neurodevelopmental, living, PntP2, MDC1D, wide, Health, People, enr, Festa, PntP1, E(E2F)3D, inherited genetic, PNTP2, neurodevelopmental disorder, Toenail, collection of teeth, PNTP1, footnotes, Mental Disorder, other disease, whole exome, 0998/12, Family Member, Procedures, FESTA-L, FESTA-S, Neurodevelopmental Disorder, ETS2, Ets2, Prospective, number, obesity disease, Perinatal Information Systems, Fetal Bloods, Information Retrieval Systems, Network, broad, teeth, Normalcies, ZTNF2, presence, LARGE1, Bloods, Child, froggy, Gyltl1a, Women, Obesity, Childhood or Adolescence, Perinatal Information System, DMPOINT1A, pntegfr, 0608/07, Conserved Sequences, Cow's Milk, Ancillary, Studies, Prospective Study, disease or disorder, Parenthood Status, Low, Trait, Technique, Stepparents, U19, Lanugo, Normalities, putative HLA-DR-associated protein I-2, study, Fingernail, BM040, Umbilical Cord, urinary levels, FOCUS, Mental Disorders Diagnosed in Childhood, A proliferation-inducing ligand, Fetal Hair, pointed-RC, occurrence, Research, MDDGB6, coat/ hair, Having too much body fat, prevalence, TNF-related death ligand 1, Pregnant Peoples, Mother, LARGE, Overweight and obesity, Research Activities., EK3-2, Genotypes, non-neoplastic, Study, l(3)07825, BPFD#36, chorda umbilicalis, Cow Milk, Cow, quill, Ages, Disorder, Cord Blood, disorder, CG17077, Development and Research, Kinship Networks, constitutitional genetic, Family, Neurodevelopmental Disorders, l(3)j1B7, incidence, Individual Health, fur, Ets, cou, Family Research, whole blood, Traits, Parental, disorders, Cords, Umbilical Cord Blood, medical condition, Ancillary Information System, claw of foot, TALL2, Woman, CD256, obesity, Trdl1, Cord, near to, Family Members, Sequences, development, mammary gland milk, count in organism, Lr, Priority, TNF- and APOL-related leukocyte expressed ligand 2, Teeth, Genogroup, Sequence, April, Systems, sequence, condition, Step-Parent, rare (European definition), hindlimb digit claw, techniques, pnt-P1, outbreaks, pnt-P2, obesity disorder, l(3)s118306, Obesity (disorder), Tall2, Normality, Obesity NOS, postnatal growth, hair, Cord Bloods, pedal claw, TRAITS, endemics, primary structure of sequence macromolecule, sample population, microchaeta, APRIL, Pregnant Person, Pregnant, Genogroups, Emergency Care Information Systems, Ets58AB, sample collection, like-glycosyltransferase, PHAPI2, approaches, Families, vicinity of, cardinality, Bra, Mental Disorders Usually Diagnosed in Infancy, epidemics, coat hair, hereditary, growth, Relatives, POINT, methodology, glycosyltransferase-like protein LARGE1, CG8705"],"pubmed_title_synonyms":["Glioma 1, Genome-Wide Association, Glioma NOS, Glioma (except Nasal glioma, GLM, glial tumors, malignant, Genome Wide Association Analysis, Whole Genome Association Study, neuroglial tumor, obsolete_glioma, Mixed Glioma, Malignant Glioma, Neuroglial Tumor, tumour of the neuroglia, Tumor, Malignant, Genome-Wide, neoplasm of neuroglia, GWA Studies, [M]Glioma NOS (morphologic abnormality), Genome Wide Association Study, tumor of the neuroglia, Studies, [M]Gliomas (morphologic abnormality), Gliomas, Mixed, Whole Genome Association Analysis, Glial Cell Tumor, [M]Glioma NOS, Mixed Gliomas, Glial Tumor, GWA Study, susceptibility, NOS (except Nasal glioma, Neuroglial Neoplasm, glioma (morphologic abnormality), Neuroglial Neoplasms, Glioma NOS (morphologic abnormality), neuroglial tumour, GWA, Glial Cell, Malignant glioma, Neoplasm of the Neuroglia, Tumor of Neuroglia, Glial Neoplasm, Genome Wide Association Studies, neuroglial neoplasm, Genome Wide Association Scan, Genome-Wide Association Studies, tumor of neuroglia, Study, Neoplasm of Neuroglia, glial tumor, no ICD-O subtype, Neoplasms of Neuroglia., Tumor of the Neuroglia, tumour of neuroglia, glial tumour, Glial Cell Tumors, Association Studies, not neoplastic), Gliomas (morphologic abnormality), Malignant Gliomas, Glioma, Association Study, glial neoplasm, [M]Gliomas, malignant (morphologic abnormality), glioma, Tumors of Neuroglia, neoplasm of the neuroglia, Tumors"],"pubmed_abstract_synonyms":["Genome-Wide Association, MTS1, B Cells, Previously, p19<ARF>, WGA study, 2410041A17Rik, ACTG, Bursa-Dependent Lymphocytes, ACTE, CDK4I Protein Variant A148T, Whole Genome Association Study, lymphoblastic, B cell, positive regulation by symbiont of host non-apoptotic programmed cell death, Pctr1, fs(1)M34, CG30327, Multifactorial Causality, Enabling, csp2, Act5, l(1)G0420, SUBTYPE, DmelCG12051, Relative, CG11478, Odds Ratios, Protoplasm., Reinforcing Factor, Treatment Effect, Associations, Causations, treatment outcome, pathogenesis, HEL-176, CG4601, ARF-INK4a, Arf, establishment and maintenance of substrate location, ARF, Influence, Ability Question, p16(INK4a), Effect, Risk Ratio, imprinted and ancient gene protein, A, strong, GWA Study, DmelCG42257, C, modification by symbiont of host biological process, cyt5C, stimulation by symbiont of host programmed cell death, DHO, Provide, CG18572, MTS-1, Genome-Wide Association Studies, Inherited Susceptibility, Type D Cyclins, B lymphocyte, Had, Ability To, act 42A, Subsequent, Cyclins, Ac5C, CG4027, ACT, P14, Act, P16, P19, Has, P16-INK4A, Organism by Subtype, Multifactorial, establishment and maintenance of substance location, CDKN2A NP_000068.1:p.A148T, l(1)G0330, Followed By, D Cyclins, Actin/BAP47, B Lymphocytes, CTE-II, Cytoplasms, pediatric, AACT, MLM, SNP Genotyping, CTE-IIa, Cyclin-Dependent Kinase Inhibitor 2A Protein Variant A148T, Ratios, act, Multiple Causations, Ach1, hBACH, p16, ACH1, LACH1, Genome-Wide, INSDC_feature:misc_RNA, act42A, Acute onset, GIG25, single organism localization, Genome Wide Association Study, Su(b), Alpha-1-antichymotrypsin His-Pro-less, CG6393, AFFX-Dros-ACTIN_M_r_at, GIG24, Relative Risks, Predisposing, modulation by symbiont of host system process, DFNA26, actin, Whole Genome Association Analysis, LACH, GAT, DFNA20, Impute, SNP ARRAY, Subtype, Dmel_CG6393, Factors, DmelCG4027, Risk, Type D, l(1)G0117, CDKN2A Ala148Thr, Predominant, common, Actin, induction by organism of programmed cell death in other organism during symbiotic interaction, beta-actin/Bap47, modification by symbiont of host morphology or physiology, Statistical Imputation, l(1)G0486, l(1)G0245, Multiple, actin5C, l(1)G0009, Treatment Outcome, ACTL3, B-Lymphocyte, Lach1, CDKN2A p.Ala148Thr, activation by symbiont of host programmed cell death, Cyclin-Dependent Kinase Inhibitor p16 Protein Variant Ala148Thr, SNP Probe, Association Study, Previous, E430016J11Rik, BACH, INK4A, Provided, establishment and maintenance of cellular component location, CDKN2, l(1)Ab, p16INK4A Protein Variant Ala148Thr, Act5c, GWAS, p16(INK4a) Protein Variant Ala148Thr, l(1)G0010, Type D Cyclin, Effects, INK4, Genome Wide Association Analysis, regulation by symbiont of host system process, Cyclin-Dependent Kinase Inhibitor 2A Protein Variant Ala148Thr, number, CDKN2A NP_000068.1:p.Ala148Thr, ACT5C, treatment effect, CG12051, Inherited Predisposition, genetic predisposition, Serpin A3, Bach, Ximpact, Therapy Effect, Cyclin-Dependent Kinase 4 Inhibitor A Protein Variant A148T, l(1)G0025, Imputed, Child Life Stage, GWA Studies, resilient, WGAS, induction by organism of non-apoptotic programmed cell death in other organism during symbiotic interaction, Therapy Outcome, tough, Predisposing Factors, Studies, establishment and maintenance of position, Cell growth-inhibiting gene 24|25 protein, Next, Pediatric, whole genome association study, Means, induction of non-apoptotic programmed cell death by other organism, act5C, B-cell, Cross-Product Ratio, Risk Ratios, Supply, NP_000068.1:p.A148T, BRWS2, GWA, Former, causes, Ratio, Genotypes, Genome Wide Association Scan, fs(1)829, Study, Odds, Act42a, anon-EST:fe2D2, Single Nucleotide Polymorphism Array, 1700027G07Rik, Ink4a|Arf, Supplied, Following, 65K, DmelCG18572, Appearance, CG42257, Dmel_CG30327, causality, CMM2, p19ARF, Type, snp, T11, Act-5C, CDK4I Protein Variant Ala148Thr, treatment_outcome, Cte-II, Possess, l(1)G0177, Multifactorial Causalities, FORMER, 42A, D Cyclin, cg11478, Cross-Product, TP16, disruption by symbiont of host cell, activation by organism of non-apoptotic programmed cell death in other organism, CPS, P16INK4, Enabling Factors, p16(INK4a) Protein Variant A148T, dJ393D12.2, Factor, Reinforcing, p19-lt-ARF-gt-, genetic susceptibility, Enabling Factor, impact-a, p16INK4a, 9p21.3, Cross-Product Ratios, CDKN2A p.A148T, NP_000068.1:p.Ala148Thr, CAD, Genome-Wide Association Analysis, Genogroup, Have, beta-actin, P14ARF, M32055, Ink4a/Arf, Act42, imprinted and ancient gene protein homolog, IMPACT, Nuclear, establishment and maintenance of localization, Multiple Causation, rare (European definition), ACTA3, effect, Causality, Predisposing Factor, Cross Product Ratio, Relative Risk, Reinforcing Factors, P16INK4A, l(1)G0079, Genotype Chip, p16-INK4 Protein Variant Ala148Thr, Causalities, Organism Subtype, p16INK4A Protein Variant A148T, Cyclin, PYR1, VSCM, CDK4I, Risks, act 5C, Bursa-Equivalent Lymphocyte, Childhood, single-organism localization, Imputation, Genome Wide Association Studies, Specified, INK4a-ARF, Genome-Wide Association Study, CDKN2A A148T, Genogroups, Relative Odds, Causation, localisation, Outcome of Therapy, Specific, p16-INK4 Protein Variant A148T, P19ARF, cardinality, Protoplasms, Genetic Susceptibility, Cyclin-Dependent Kinase Inhibitor p16 Protein Variant A148T, Association Studies, DRORUD, BAP47, ACTSG, genome-wide association study, B-lymphocyte, Bap47, Cyclin-Dependent Kinase 4 Inhibitor A Protein Variant Ala148Thr, RWDD5, Actin5C, Main"],"additional_accession":[]},"is_claimable":false,"name":"UK10K COHORT ALSPAC","description":"The UK10K project proposes a series of complementary genetic approaches to find new low-frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome-wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein-coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will directly analyse quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches.\n\nThe Avon Longitudinal Study of Parents and Children (ALSPAC) is a two-generation prospective study. Pregnant women living in one of three health districts in the former county of Avon with an expected delivery date between April 1991 and December 1992 were eligible to be enrolled in the study, and this formed the initial point of contact for the development of a large, family based resource.\n\nInformation has been collected on the children and the mothers through retrieval of biological materials (e.g. antenatal blood samples, placentas), biological sampling (e.g. collection of cord blood, umbilical cord, milk teeth, hair, toenails, blood and urine), self-administered questionnaires, data extraction from medical notes, linkage to routine information systems and at repeat research clinics.","dates":{"updated":"2021-04-23 20:10:07"},"accession":"EGAS00001000090","cross_references":{"TAXONOMY":["9606"],"pubmed":["24343240","26463672","25826619","26424050"],"EGA":["EGAD00001000195","EGAD00001000789","EGAD00001000740","EGAC00001000205"]}}