Novel method for combined linkage and genome-wide association analysis finds evidence of distinct genetic architecture for two subtypes of autism

Detalhes bibliográficos
Autor(a) principal: Vieland, V.J.
Data de Publicação: 2011
Outros Autores: Hallmayer, J., Huang, Y., Pagnamenta, A.T., Pinto, D., Khan, H., Monaco, A.P., Paterson, A.D., Scherer, S.W., Sutcliffe, J.S., Szatmari, P., The Autism Genome Project (AGP)
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.18/311
Resumo: Member of the Autism Genome Project Consortium: Astrid M. Vicente
id RCAP_a510cbaace2f14a1926cff722eb3506c
oai_identifier_str oai:repositorio.insa.pt:10400.18/311
network_acronym_str RCAP
network_name_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository_id_str 7160
spelling Novel method for combined linkage and genome-wide association analysis finds evidence of distinct genetic architecture for two subtypes of autismAutismLinkage analysisGenome-wide associationPPLPPLDIQPerturbações do Desenvolvimento Infantil e Saúde MentalMember of the Autism Genome Project Consortium: Astrid M. VicenteThe Autism Genome Project has assembled two large datasets originally designed for linkage analysis and genome-wide association analysis, respectively: 1,069 multiplex families genotyped on the Affymetrix 10 K platform, and 1,129 autism trios genotyped on the Illumina 1 M platform. We set out to exploit this unique pair of resources by analyzing the combined data with a novel statistical method, based on the PPL statistical framework, simultaneously searching for linkage and association to loci involved in autism spectrum disorders (ASD). Our analysis also allowed for potential differences in genetic architecture for ASD in the presence or absence of lower IQ, an important clinical indicator of ASD subtypes. We found strong evidence of multiple linked loci; however, association evidence implicating specific genes was low even under the linkage peaks. Distinct loci were found in the lower IQ families, and these families showed stronger and more numerous linkage peaks, while the normal IQ group yielded the strongest association evidence. It appears that presence/absence of lower IQ (LIQ) demarcates more genetically homogeneous subgroups of ASD patients, with not just different sets of loci acting in the two groups, but possibly distinct genetic architecture between them, such that the LIQ group involves more major gene effects (amenable to linkage mapping), while the normal IQ group potentially involves more common alleles with lower penetrances. The possibility of distinct genetic architecture across subtypes of ASD has implications for further research and perhaps for research approaches to other complex disorders as well.SpringerRepositório Científico do Instituto Nacional de SaúdeVieland, V.J.Hallmayer, J.Huang, Y.Pagnamenta, A.T.Pinto, D.Khan, H.Monaco, A.P.Paterson, A.D.Scherer, S.W.Sutcliffe, J.S.Szatmari, P.The Autism Genome Project (AGP)2011-11-05T10:03:47Z2011-062011-06-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/311engJ Neurodev Disord. 2011 Jun;3(2):113-123. Epub 2011 Jan 191866-1947doi:10.1007/s11689-011-9072-9info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-20T15:38:07Zoai:repositorio.insa.pt:10400.18/311Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:35:32.153773Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Novel method for combined linkage and genome-wide association analysis finds evidence of distinct genetic architecture for two subtypes of autism
title Novel method for combined linkage and genome-wide association analysis finds evidence of distinct genetic architecture for two subtypes of autism
spellingShingle Novel method for combined linkage and genome-wide association analysis finds evidence of distinct genetic architecture for two subtypes of autism
Vieland, V.J.
Autism
Linkage analysis
Genome-wide association
PPL
PPLD
IQ
Perturbações do Desenvolvimento Infantil e Saúde Mental
title_short Novel method for combined linkage and genome-wide association analysis finds evidence of distinct genetic architecture for two subtypes of autism
title_full Novel method for combined linkage and genome-wide association analysis finds evidence of distinct genetic architecture for two subtypes of autism
title_fullStr Novel method for combined linkage and genome-wide association analysis finds evidence of distinct genetic architecture for two subtypes of autism
title_full_unstemmed Novel method for combined linkage and genome-wide association analysis finds evidence of distinct genetic architecture for two subtypes of autism
title_sort Novel method for combined linkage and genome-wide association analysis finds evidence of distinct genetic architecture for two subtypes of autism
author Vieland, V.J.
author_facet Vieland, V.J.
Hallmayer, J.
Huang, Y.
Pagnamenta, A.T.
Pinto, D.
Khan, H.
Monaco, A.P.
Paterson, A.D.
Scherer, S.W.
Sutcliffe, J.S.
Szatmari, P.
The Autism Genome Project (AGP)
author_role author
author2 Hallmayer, J.
Huang, Y.
Pagnamenta, A.T.
Pinto, D.
Khan, H.
Monaco, A.P.
Paterson, A.D.
Scherer, S.W.
Sutcliffe, J.S.
Szatmari, P.
The Autism Genome Project (AGP)
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório Científico do Instituto Nacional de Saúde
dc.contributor.author.fl_str_mv Vieland, V.J.
Hallmayer, J.
Huang, Y.
Pagnamenta, A.T.
Pinto, D.
Khan, H.
Monaco, A.P.
Paterson, A.D.
Scherer, S.W.
Sutcliffe, J.S.
Szatmari, P.
The Autism Genome Project (AGP)
dc.subject.por.fl_str_mv Autism
Linkage analysis
Genome-wide association
PPL
PPLD
IQ
Perturbações do Desenvolvimento Infantil e Saúde Mental
topic Autism
Linkage analysis
Genome-wide association
PPL
PPLD
IQ
Perturbações do Desenvolvimento Infantil e Saúde Mental
description Member of the Autism Genome Project Consortium: Astrid M. Vicente
publishDate 2011
dc.date.none.fl_str_mv 2011-11-05T10:03:47Z
2011-06
2011-06-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.18/311
url http://hdl.handle.net/10400.18/311
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv J Neurodev Disord. 2011 Jun;3(2):113-123. Epub 2011 Jan 19
1866-1947
doi:10.1007/s11689-011-9072-9
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
_version_ 1799132081481056256