Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/108274
DC Field | Value | Language |
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dc.contributor.author | Oliveira, Guiomar | - |
dc.contributor.author | Mouga, Susana | - |
dc.contributor.author | Duque, Frederico | - |
dc.contributor.author | Café, Cátia | - |
dc.contributor.author | Almeida, Joana | - |
dc.contributor.author | The Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium | - |
dc.date.accessioned | 2023-08-22T09:07:51Z | - |
dc.date.available | 2023-08-22T09:07:51Z | - |
dc.date.issued | 2017 | - |
dc.identifier.issn | 2040-2392 | pt |
dc.identifier.uri | https://hdl.handle.net/10316/108274 | - |
dc.description.abstract | Background: Over the past decade genome-wide association studies (GWAS) have been applied to aid in the understanding of the biology of traits. The success of this approach is governed by the underlying effect sizes carried by the true risk variants and the corresponding statistical power to observe such effects given the study design and sample size under investigation. Previous ASD GWAS have identified genome-wide significant (GWS) risk loci; however, these studies were of only of low statistical power to identify GWS loci at the lower effect sizes (odds ratio (OR) <1.15). Methods: We conducted a large-scale coordinated international collaboration to combine independent genotyping data to improve the statistical power and aid in robust discovery of GWS loci. This study uses genome-wide genotyping data from a discovery sample (7387 ASD cases and 8567 controls) followed by meta-analysis of summary statistics from two replication sets (7783 ASD cases and 11359 controls; and 1369 ASD cases and 137308 controls). Results: We observe a GWS locus at 10q24.32 that overlaps several genes including PITX3, which encodes a transcription factor identified as playing a role in neuronal differentiation and CUEDC2 previously reported to be associated with social skills in an independent population cohort. We also observe overlap with regions previously implicated in schizophrenia which was further supported by a strong genetic correlation between these disorders (Rg = 0.23; P=9 ×10−6). We further combined these Psychiatric Genomics Consortium (PGC) ASD GWAS data with the recent PGC schizophrenia GWAS to identify additional regions which may be important in a common neurodevelopmental phenotype and identified 12 novel GWS loci. These include loci previously implicated in ASD such as FOXP1 at 3p13, ATP2B2 at 3p25.3, and a ‘neurodevelopmental hub’ on chromosome 8p11.23. Conclusions: This study is an important step in the ongoing endeavour to identify the loci which underpin the common variant signal in ASD. In addition to novel GWS loci, we have identified a significant genetic correlation with schizophrenia and association of ASD with several neurodevelopmental-related genes such as EXT1, ASTN2, MACROD2, and HDAC4. | pt |
dc.description.sponsorship | The Autism Working Group of the Psychiatric Genomics Consortium was supported by National Institutes of Mental Health (NIMH, USA) grant MH109539, MH094432 and MH094421 to M.J.D. The ACE Network was supported by MH081754 and MH100027 to D.H.G. The Autism Genetic Resource Exchange (AGRE) is a program of Autism Speaks (USA) and was supported by grant MH081810. The Autism Genome Project (AGP) was supported by grants from Autism Speaks, the Canadian Institutes of Health Research (CIHR), Genome Canada, the Health Research Board (Ireland; AUT/ 2006/1, AUT/2006/2, PD/2006/48), the Hilibrand Foundation (USA), the Medical Research Council (UK), the National Institutes of Health (USA; the National Institute of Child Health and Human Development and the National Institute of Mental Health), the Ontario Genomics Institute, and the University of Toronto McLaughlin Centre. The Simons Simplex Collection (SSC) was supported by a grant from the Simons Foundation (SFARI 124827 to the investigators of the Simons Simplex Collection Genetic Consortium); approved researchers can obtain the SSC population dataset described in this study (http://sfari.org/resources/sfari-base) by applying at https:// base.sfari.org. The Gene Discovery Project of Johns Hopkins was funded by MH060007, MH081754, and the Simons Foundation. The MonBos Collection study was funded in part through a grant from the Autism Consortium of Boston. Support for the Extreme Discordant Sib-Pair (EDSP) family sample (part of the MonBos collection) was provided by the NLM Family foundation. Support for the Massachusetts General Hospital (MGH)–Finnish collaborative sample was provided by NARSAD. The PAGES collection was funded by NIMH grant MH097849. The collection of data and biomaterials that participated in the NIMH Autism Genetics Initiative has been supported by National Institute of Health grants MH52708, MH39437, MH00219, and MH00980; National Health Medical Research Council grant 0034328; and by grants from the Scottish Rite, the Spunk Fund, Inc., the Rebecca and Solomon Baker Fund, the APEX Foundation, the National Alliance for Research in Schizophrenia and Affective Disorders (NARSAD), the endowment fund of the Nancy Pritzker Laboratory (Stanford); and by gifts from the Autism Society of America, the Janet M. Grace Pervasive Developmental Disorders Fund, and families and friends of individuals with autism. The iPSYCH project is funded by The Lundbeck Foundation and the universities and university hospitals of Aarhus and Copenhagen. In addition, the genotyping of iPSYCH samples was supported by grants from the Stanley Foundation, the Simons Foundation (SFARI 311789 to MJD), and NIMH (5U01MH094432-02 to MJD). The Study to Explore Early Development (SEED) was funded by the Centers for Disease Control and Prevention (CDC) grants U10DD000180, U10DD000181, U10DD000182, U10DD000183, U10DD000184, and U10DD000498. Statistical analyses were carried out on the Genetic Cluster Computer (http:// www.geneticcluster.org) hosted by SURFsara and financially supported by the Netherlands Scientific Organization (NWO 480-05-003), along with a supplement from the Dutch Brain Foundation and the VU University Amsterdam. Additional statistical analyses were performed and supported by the Trinity Centre for High Performance Computing (http://www.tchpc.tcd.ie/) funded through Science Foundation Ireland. Computational support for the PAGES collection was provided in part through the computational resources and staff expertise of the Department of Scientific Computing at the Icahn School of Medicine at Mount Sinai (https://hpc.mssm.edu). Data QC and statistical analyses of the iPSYCH samples were performed at the high-performance computing cluster GenomeDK (http://genome.au.dk) at the Center for Integrative Sequencing, iSEQ, Aarhus University. iSEQ provided computed time, data storage, and technical support for the study. | pt |
dc.language.iso | eng | pt |
dc.publisher | Springer Nature | pt |
dc.rights | openAccess | pt |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | pt |
dc.subject | Autism spectrum disorder | pt |
dc.subject | Genome-wide association study | pt |
dc.subject | Meta-analysis | pt |
dc.subject | Genetic correlation | pt |
dc.subject | Heritability | pt |
dc.subject | Gene-set analysis | pt |
dc.subject | Schizophrenia | pt |
dc.subject | Neurodevelopment | pt |
dc.subject.mesh | Adaptor Proteins, Signal Transducing | pt |
dc.subject.mesh | Autism Spectrum Disorder | pt |
dc.subject.mesh | Carrier Proteins | pt |
dc.subject.mesh | Case-Control Studies | pt |
dc.subject.mesh | Chromosomes, Human, Pair 10 | pt |
dc.subject.mesh | Female | pt |
dc.subject.mesh | Forkhead Transcription Factors | pt |
dc.subject.mesh | Gene Expression | pt |
dc.subject.mesh | Genome-Wide Association Study | pt |
dc.subject.mesh | Homeodomain Proteins | pt |
dc.subject.mesh | Humans | pt |
dc.subject.mesh | Male | pt |
dc.subject.mesh | Membrane Proteins | pt |
dc.subject.mesh | Plasma Membrane Calcium-Transporting ATPases | pt |
dc.subject.mesh | Repressor Proteins | pt |
dc.subject.mesh | Schizophrenia | pt |
dc.subject.mesh | Transcription Factors | pt |
dc.subject.mesh | Genetic Loci | pt |
dc.subject.mesh | Genetic Predisposition to Disease | pt |
dc.title | Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia | pt |
dc.type | article | - |
degois.publication.firstPage | 21 | pt |
degois.publication.issue | 1 | pt |
degois.publication.title | Molecular Autism | pt |
dc.peerreviewed | yes | pt |
dc.identifier.doi | 10.1186/s13229-017-0137-9 | pt |
degois.publication.volume | 8 | pt |
dc.date.embargo | 2017-01-01 | * |
uc.date.periodoEmbargo | 0 | pt |
item.grantfulltext | open | - |
item.cerifentitytype | Publications | - |
item.languageiso639-1 | en | - |
item.openairetype | article | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.fulltext | Com Texto completo | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.researchunit | ICNAS - Institute for Nuclear Sciences Applied to Health | - |
crisitem.author.orcid | 0000-0003-4031-3880 | - |
crisitem.author.orcid | 0000-0003-1072-4208 | - |
Appears in Collections: | FMUC Medicina - Artigos em Revistas Internacionais |
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