Partitioning the heritability of tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture

Detalhes bibliográficos
Autor(a) principal: Davis, Lea K.
Data de Publicação: 2013
Outros Autores: Yu, Dongmei, Keenan, Clare L., Gamazon, Eric R., Konkashbaev, Anuar I., Derks, Eske M., Sampaio, Aline S.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UFBA
Texto Completo: http://repositorio.ufba.br/ri/handle/ri/16374
Resumo: p. 1-14
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spelling Davis, Lea K.Yu, DongmeiKeenan, Clare L.Gamazon, Eric R.Konkashbaev, Anuar I.Derks, Eske M.Sampaio, Aline S.Davis, Lea K.Yu, DongmeiKeenan, Clare L.Gamazon, Eric R.Konkashbaev, Anuar I.Derks, Eske M.Sampaio, Aline S.2014-10-10T15:05:44Z2014-10-10T15:05:44Z20131553-7390http://repositorio.ufba.br/ri/handle/ri/16374v. 9, n. 10p. 1-14The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.Submitted by Suelen Reis (suziy.ellen@gmail.com) on 2014-04-24T14:04:29Z No. of bitstreams: 1 10.1371journal.pgen.1003864.pdf: 652592 bytes, checksum: 437d2a27dc80379e2b90d7ee691207ec (MD5)Approved for entry into archive by Rodrigo Meirelles (rodrigomei@ufba.br) on 2014-10-10T15:05:44Z (GMT) No. of bitstreams: 1 10.1371journal.pgen.1003864.pdf: 652592 bytes, checksum: 437d2a27dc80379e2b90d7ee691207ec (MD5)Made available in DSpace on 2014-10-10T15:05:44Z (GMT). No. of bitstreams: 1 10.1371journal.pgen.1003864.pdf: 652592 bytes, checksum: 437d2a27dc80379e2b90d7ee691207ec (MD5) Previous issue date: 2013http://dx.doi.org/10.1371/journal.pgen.1003864reponame:Repositório Institucional da UFBAinstname:Universidade Federal da Bahia (UFBA)instacron:UFBAPartitioning the heritability of tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecturePLoS Geneticsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessengLICENSElicense.txtlicense.txttext/plain1345https://repositorio.ufba.br/bitstream/ri/16374/2/license.txt0d4b811ef71182510d2015daa7c8a900MD52ORIGINAL10.1371journal.pgen.1003864.pdf10.1371journal.pgen.1003864.pdfapplication/pdf652592https://repositorio.ufba.br/bitstream/ri/16374/1/10.1371journal.pgen.1003864.pdf437d2a27dc80379e2b90d7ee691207ecMD51TEXT10.1371journal.pgen.1003864.pdf.txt10.1371journal.pgen.1003864.pdf.txtExtracted texttext/plain88904https://repositorio.ufba.br/bitstream/ri/16374/3/10.1371journal.pgen.1003864.pdf.txtd174df1f9c9c729635ada39364bb2a50MD53ri/163742022-08-08 13:17:52.271oai:repositorio.ufba.br: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Repositório InstitucionalPUBhttp://192.188.11.11:8080/oai/requestopendoar:19322022-08-08T16:17:52Repositório Institucional da UFBA - Universidade Federal da Bahia (UFBA)false
dc.title.pt_BR.fl_str_mv Partitioning the heritability of tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture
dc.title.alternative.pt_BR.fl_str_mv PLoS Genetics
title Partitioning the heritability of tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture
spellingShingle Partitioning the heritability of tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture
Davis, Lea K.
title_short Partitioning the heritability of tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture
title_full Partitioning the heritability of tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture
title_fullStr Partitioning the heritability of tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture
title_full_unstemmed Partitioning the heritability of tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture
title_sort Partitioning the heritability of tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture
author Davis, Lea K.
author_facet Davis, Lea K.
Yu, Dongmei
Keenan, Clare L.
Gamazon, Eric R.
Konkashbaev, Anuar I.
Derks, Eske M.
Sampaio, Aline S.
author_role author
author2 Yu, Dongmei
Keenan, Clare L.
Gamazon, Eric R.
Konkashbaev, Anuar I.
Derks, Eske M.
Sampaio, Aline S.
author2_role author
author
author
author
author
author
dc.contributor.author.fl_str_mv Davis, Lea K.
Yu, Dongmei
Keenan, Clare L.
Gamazon, Eric R.
Konkashbaev, Anuar I.
Derks, Eske M.
Sampaio, Aline S.
Davis, Lea K.
Yu, Dongmei
Keenan, Clare L.
Gamazon, Eric R.
Konkashbaev, Anuar I.
Derks, Eske M.
Sampaio, Aline S.
description p. 1-14
publishDate 2013
dc.date.issued.fl_str_mv 2013
dc.date.accessioned.fl_str_mv 2014-10-10T15:05:44Z
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dc.identifier.number.pt_BR.fl_str_mv v. 9, n. 10
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