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Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture
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نویسنده
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davis l.k. ,yu d. ,keenan c.l. ,gamazon e.r. ,konkashbaev a.i. ,derks e.m. ,neale b.m. ,yang j. ,lee s.h. ,evans p. ,barr c.l. ,bellodi l. ,benarroch f. ,berrio g.b. ,bienvenu o.j. ,bloch m.h. ,blom r.m. ,bruun r.d. ,budman c.l. ,camarena b. ,campbell d. ,cappi c. ,cardona silgado j.c. ,cath d.c. ,cavallini m.c. ,chavira d.a. ,chouinard s. ,conti d.v. ,cook e.h. ,coric v. ,cullen b.a. ,deforce d. ,delorme r. ,dion y. ,edlund c.k. ,egberts k. ,falkai p. ,fernandez t.v. ,gallagher p.j. ,garrido h. ,geller d. ,girard s.l. ,grabe h.j. ,grados m.a. ,greenberg b.d. ,gross-tsur v. ,haddad s. ,heiman g.a. ,hemmings s.m.j. ,hounie a.g. ,illmann c. ,jankovic j. ,jenike m.a. ,kennedy j.l. ,king r.a. ,kremeyer b. ,kurlan r. ,lanzagorta n. ,leboyer m. ,leckman j.f. ,lennertz l. ,liu c. ,lochner c. ,lowe t.l. ,macciardi f. ,mccracken j.t. ,mcgrath l.m. ,mesa restrepo s.c. ,moessner r. ,morgan j. ,muller h. ,murphy d.l. ,naarden a.l. ,ochoa w.c. ,ophoff r.a. ,osiecki l. ,pakstis a.j. ,pato m.t. ,pato c.n. ,piacentini j. ,pittenger c. ,pollak y. ,rauch s.l. ,renner t.j. ,reus v.i. ,richter m.a. ,riddle m.a. ,robertson m.m. ,romero r. ,rosàrio m.c. ,rosenberg d. ,rouleau g.a. ,ruhrmann s. ,ruiz-linares a. ,sampaio a.s. ,samuels j. ,sandor p. ,sheppard b. ,singer h.s. ,smit j.h. ,stein d.j. ,strengman e. ,tischfield j.a. ,valencia duarte a.v. ,vallada h. ,van nieuwerburgh f. ,veenstra-vanderweele j. ,walitza s. ,wang y. ,wendland j.r. ,westenberg h.g.m. ,shugart y.y. ,miguel e.c. ,mcmahon w. ,wagner m. ,nicolini h. ,posthuma d. ,hanna g.l. ,heutink p. ,denys d. ,arnold p.d. ,oostra b.a. ,nestadt g. ,freimer n.b. ,pauls d.l. ,wray n.r. ,stewart s.e. ,mathews c.a. ,knowles j.a. ,cox n.j. ,scharf j.m.
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منبع
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plos genetics - 2013 - دوره : 9 - شماره : 10
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چکیده
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The 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.
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آدرس
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section of genetic medicine,department of medicine,university of chicago,chicago,il, United States, psychiatric and neurodevelopmental genetics unit,center for human genetics research,department of psychiatry,harvard medical school,massachusetts general hospital,boston,ma,united states,stanley center for psychiatric research,broad institute of harvard and mit,cambridge,ma, United States, department of medicine,university of chicago,chicago,il,united states,department of human genetics,university of chicago,chicago,il, United States, section of genetic medicine,department of medicine,university of chicago,chicago,il, United States, section of genetic medicine,department of medicine,university of chicago,chicago,il, United States, department of psychiatry,academic medical center,university of amsterdam,amsterdam, Netherlands, stanley center for psychiatric research,broad institute of harvard and mit,cambridge,ma,united states,analytic and translational genetics unit,massachusetts general hospital,boston,ma, United States, the university of queensland,diamantina institute,queensland,australia,the university of queensland,queensland brain institute,queensland, Australia, the university of queensland,queensland brain institute,queensland, Australia, section of genetic medicine,department of medicine,university of chicago,chicago,il, United States, the toronto western research institute,university health network,toronto,on,canada,the hospital for sick children,toronto,on, Canada, università vita-salute san raffaele,milano, Italy, herman dana division of child and adolescent psychiatry,hadassah-hebrew university medical center,jerusalem, Israel, universidad de antioquia,universidad pontificia bolivariana,medellín, Colombia, department of psychiatry and behavioral sciences,johns hopkins university school of medicine,baltimore,md, United States, department of psychiatry,yale university,new haven,ct,united states,child study center,yale university school of medicine,new haven,ct, United States, department of psychiatry,academic medical center,university of amsterdam,amsterdam, Netherlands, north shore-long island jewish medical center,manhasset,ny,united states,new york university medical center,new york,ny, United States, north shore-long island jewish health system,manhasset,ny,united states,hofstra university school of medicine,hempstead,ny, United States, instituto nacional de psiquiatría ramon de la fuente muñiz,mexico city, Mexico, university college london,london,united kingdom,department of psychiatry,university of hong kong,hong kong, China, department of psychiatry,university of são paulo medical school,são paulo, Brazil, universidad de antioquia,universidad pontificia bolivariana,medellín, Colombia, department of psychiatry,vu university medical center,amsterdam,netherlands,department of clinical and health psychology,utrecht university,utrecht,netherlands,altrecht academic anxiety center,utrecht, Netherlands, ospedale san raffaele,milano, Italy, department of psychology,university of california los angeles,los angeles,ca,united states,department of psychiatry,university of california san diego,la jolla,ca, United States, university of montreal,montreal,qc, Canada, department of preventative medicine,division of biostatistics,keck school of medicine,university of southern california,los angeles,ca, United States, institute for juvenile research,department of psychiatry,university of illinois at chicago,chicago,il, United States, department of psychiatry,yale university,new haven,ct, United States, department of psychiatry and behavioral sciences,johns hopkins university school of medicine,baltimore,md, United States, laboratory of pharmaceutical biotechnology,ghent university,ghent, Belgium, human genetics and cognitive functions,institut pasteur,paris,france,fondation fondamental,french national science foundation,creteil,france,ap-hp,robert debré hospital,department of child and adolescent psychiatry,paris, France, department of psychiatry,university of montreal,montreal,qc, Canada, department of preventative medicine,division of biostatistics,keck school of medicine,university of southern california,los angeles,ca, United States, department of child and adolescent psychiatry,psychosomatics and psychotherapy,university of würzburg,würzburg, Germany, department of psychiatry and psychotherapy,university of munich,munich, Germany, child study center,yale university school of medicine,new haven,ct,united states,department of psychiatry,yale university school of medicine,new haven,ct, United States, psychiatric and neurodevelopmental genetics unit,center for human genetics research,department of psychiatry,harvard medical school,massachusetts general hospital,boston,ma, United States, clinica herrera amighetti,avenida escazú,san josé, Costa Rica, ocd program,department of psychiatry,massachusetts general hospital,harvard medical school,boston,ma, United States, university of montreal,montreal,qc, Canada, department of psychiatry and psychotherapy,helios-hospital stralsund,university medicine greifswald,greifswald, Germany, department of psychiatry and behavioral sciences,johns hopkins university school of medicine,baltimore,md, United States, department of psychiatry and human behavior,brown medical school,butler hospital,providence,ri, United States, neuropediatric unit,shaare zedek medical center,jerusalem, Israel, psychiatric and neurodevelopmental genetics unit,center for human genetics research,department of psychiatry,harvard medical school,massachusetts general hospital,boston,ma, United States, department of genetics,human genetics institute of new jersey,rutgers university,piscataway,nj, United States, department of psychiatry,university of stellenbosch,stellenbosch, South Africa, department of psychiatry, Brazil, psychiatric and neurodevelopmental genetics unit,center for human genetics research,department of psychiatry,harvard medical school,massachusetts general hospital,boston,ma, United States, parkinson's disease center and movement disorders clinic,department of neurology,baylor college of medicine,houston,tx, United States, department of psychiatry,massachusetts general hospital,boston,ma, United States, neurogenetics section,centre for addiction and mental health,toronto,on,canada,department of psychiatry,university of toronto,toronto,on, Canada, yale child study center,department of genetics,yale university school of medicine,new haven,ct, United States, university college london,london, United Kingdom, atlantic neuroscience institute,overlook hospital,summit,nj, United States, carracci medical group,mexico city, Mexico, fondation fondamental,french national science foundation,creteil,france,ap-hp,robert debré hospital,department of child and adolescent psychiatry,paris,france,institut mondor de recherche biomédicale,psychiatric genetics,créteil, France, child study center,psychiatry,pediatrics and psychology,yale university,new haven,ct, United States, department of psychiatry and psychotherapy,university of bonn,bonn, Germany, department of psychiatry,institute of human genetics,university of illinois at chicago,chicago,il, United States, mrc unit on anxiety and stress disorders,department of psychiatry,university of stellenbosch,stellenbosch, South Africa, department of psychiatry,university of california at san francisco,san francisco,ca, United States, department of psychiatry and human behavior,school of medicine,university of california irvine (uci),irvine,ca, United States, department of psychiatry and human behavior,school of medicine,university of california irvine (uci),irvine,ca, United States, psychiatric and neurodevelopmental genetics unit,center for human genetics research,department of psychiatry,harvard medical school,massachusetts general hospital,boston,ma, United States, universidad de antioquia,universidad pontificia bolivariana,medellín, Colombia, department of psychiatry and psychotherapy,university of bonn,bonn, Germany, university of utah,salt lake city,ut, United States, university college london,london, United Kingdom, laboratory of clinical science,nimh intramural research program,bethesda,md, United States, department of clinical research,medical city dallas hospital,dallas,tx, United States, universidad de antioquia,universidad pontificia bolivariana,medellín, Colombia, department of psychiatry,rudolf magnus institute of neuroscience,university medical center,utrecht,netherlands,center for neurobehavioral genetics,semel institute for neuroscience and human behavior,university of california los angeles,los angeles,ca, United States, psychiatric and neurodevelopmental genetics unit,center for human genetics research,department of psychiatry,harvard medical school,massachusetts general hospital,boston,ma, United States, department of genetics,yale university school of medicine,new haven,ct, United States, department of psychiatry and the behavioral sciences,zilkha neurogenetic institute,keck school of medicine,university of southern california,los angeles,ca, United States, department of psychiatry and the behavioral sciences,zilkha neurogenetic institute,keck school of medicine,university of southern california,los angeles,ca, United States, department of psychiatry and biobehavioral sciences,university of california,los angeles,david geffen school of medicine,los angeles,ca, United States, departments of psychiatry and psychology and the child study center,yale university,new haven,ct, United States, neuropediatric unit,shaare zedek medical center,jerusalem, Israel, partners psychiatry and mclean hospital,boston,ma, United States, department of child and adolescent psychiatry,psychosomatics and psychotherapy,university of würzburg,würzburg, Germany, department of psychiatry,university of california at san francisco,san francisco,ca, United States, department of psychiatry,university of toronto,toronto,on,canada,frederick w. thompson anxiety disorders centre,sunnybrook health sciences centre,toronto,on, Canada, department of psychiatry and behavioral sciences,johns hopkins university school of medicine,baltimore,md, United States, university college london,london,united kingdom,st george's hospital and medical school,london, United Kingdom, hospital nacional de niños,san jose, Costa Rica, child and adolescent psychiatry unit (upia),department of psychiatry,federal university of são paulo,são paulo, Brazil, department of psychiatry and behavioral neurosciences,wayne state university and the detroit medical center,detroit,mi, United States, montreal neurological institute,mcgill university,montreal,qc, Canada, department of psychiatry and psychotherapy,university of cologne,cologne, Germany, university college london,london, United Kingdom, department of psychiatry,brazil,university health care services - smurb,universidade federal da bahia,salvador,bahia, Brazil, department of psychiatry and behavioral sciences,johns hopkins university school of medicine,baltimore,md, United States, department of psychiatry,university of toronto and university health network,toronto western research institute and youthdale treatment centers,toronto,on, Canada, department of psychiatry,university of california at san francisco,san francisco,ca, United States, johns hopkins university school of medicine,baltimore,md, United States, department of psychiatry,vu university medical center,amsterdam, Netherlands, university of cape town,cape town, South Africa, department of medical genetics,university medical center utrecht,utrecht, Netherlands, department of genetics,human genetics institute of new jersey,rutgers university,piscataway,nj, United States, universidad de antioquia,universidad pontificia bolivariana,medellín, Colombia, department of psychiatry,university of são paulo medical school,são paulo, Brazil, laboratory of pharmaceutical biotechnology,ghent university,ghent, Belgium, departments of psychiatry,pediatrics,and pharmacology,kennedy center for research on human development,and brain institute,vanderbilt university,nashville,tn, United States, department of child and adolescent psychiatry,university of zurich,zurich,switzerland,department of child and adolescent psychiatry,university of würzburg,würzburg, Germany, department of psychiatry and behavioral sciences,johns hopkins university school of medicine,baltimore,md, United States, laboratory of clinical science,nimh intramural research program,bethesda,md, United States, department of psychiatry,academic medical center and netherlands institute for neuroscience,institute of the royal netherlands academy of arts and sciences (nin-knaw),amsterdam, Netherlands, unit on statistical genomics,nimh intramural research program,bethesda,md, United States, department of psychiatry,university of são paulo medical school,são paulo, Brazil, department of psychiatry,university of utah,salt lake city,ut, United States, department of psychiatry and psychotherapy,university of bonn,bonn, Germany, national institute of genomic medicine-sap,carracci medical group,mexico city, Mexico, department of functional genomics,center for neurogenomics and cognitive research,neuroscience campus amsterdam,vu university amsterdam,de boelelaan,amsterdam,netherlands,department of clinical genetics,vu medical centre,de boelelaan,amsterdam,netherlands,department of child and adolescent psychiatry,erasmus university medical centre,rotterdam, Netherlands, department of psychiatry,university of michigan,ann arbor,mi, United States, section of medical genomics,department of clinical genetics,vu university medical center,amsterdam,netherlands,german center for neurodegenerative diseases,tübingen, Germany, department of psychiatry,academic medical center,university of amsterdam,amsterdam,netherlands,netherlands institute for neuroscience,institute of the royal netherlands academy of arts and sciences (nin-knaw),amsterdam, Netherlands, department of psychiatry,university of toronto,toronto,on,canada,program in genetics and genome biology,the hospital for sick children,toronto,on, Canada, department of clinical genetics,erasmus medical center,rotterdam, Netherlands, department of psychiatry and behavioral sciences,johns hopkins university school of medicine,baltimore,md, United States, center for neurobehavioral genetics,semel institute for neuroscience and human behavior,university of california los angeles,los angeles,ca, United States, psychiatric and neurodevelopmental genetics unit,center for human genetics research,department of psychiatry,harvard medical school,massachusetts general hospital,boston,ma, United States, the university of queensland,queensland brain institute,queensland, Australia, department of psychiatry,massachusetts general hospital,boston,ma,united states,british columbia mental health and addictions research institute,university of british columbia,vancouver,bc, Canada, department of psychiatry,university of california at san francisco,san francisco,ca, United States, department of psychiatry and the behavioral sciences,zilkha neurogenetic institute,keck school of medicine,university of southern california,los angeles,ca, United States, section of genetic medicine,department of medicine,university of chicago,chicago,il, United States, psychiatric and neurodevelopmental genetics unit,center for human genetics research,department of psychiatry,harvard medical school,massachusetts general hospital,boston,ma,united states,stanley center for psychiatric research,broad institute of harvard and mit,cambridge,ma,united states,division of cognitive and behavioral neurology,brigham and womens hospital,boston,ma,united states,department of neurology,massachusetts general hospital,boston,ma, United States
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Authors
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