Partitioning the heritability of Tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture.
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 explaine...
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| author | Lea K Davis Dongmei Yu Clare L Keenan Eric R Gamazon Anuar I Konkashbaev Eske M Derks Benjamin M Neale Jian Yang S Hong Lee Patrick Evans Cathy L Barr Laura Bellodi Fortu Benarroch Gabriel Bedoya Berrio Oscar J Bienvenu Michael H Bloch Rianne M Blom Ruth D Bruun Cathy L Budman Beatriz Camarena Desmond Campbell Carolina Cappi Julio C Cardona Silgado Danielle C Cath Maria C Cavallini Denise A Chavira Sylvain Chouinard David V Conti Edwin H Cook Vladimir Coric Bernadette A Cullen Dieter Deforce Richard Delorme Yves Dion Christopher K Edlund Karin Egberts Peter Falkai Thomas V Fernandez Patience J Gallagher Helena Garrido Daniel Geller Simon L Girard Hans J Grabe Marco A Grados Benjamin D Greenberg Varda Gross-Tsur Stephen Haddad Gary A Heiman Sian M J Hemmings Ana G Hounie Cornelia Illmann Joseph Jankovic Michael A Jenike James L Kennedy Robert A King Barbara Kremeyer Roger Kurlan Nuria Lanzagorta Marion Leboyer James F Leckman Leonhard Lennertz Chunyu Liu Christine Lochner Thomas L Lowe Fabio Macciardi James T McCracken Lauren M McGrath Sandra C Mesa Restrepo Rainald Moessner Jubel Morgan Heike Muller Dennis L Murphy Allan L Naarden William Cornejo Ochoa Roel A Ophoff Lisa Osiecki Andrew J Pakstis Michele T Pato Carlos N Pato John Piacentini Christopher Pittenger Yehuda Pollak Scott L Rauch Tobias J Renner Victor I Reus Margaret A Richter Mark A Riddle Mary M Robertson Roxana Romero Maria C Rosàrio David Rosenberg Guy A Rouleau Stephan Ruhrmann Andres Ruiz-Linares Aline S Sampaio Jack Samuels Paul Sandor Brooke Sheppard Harvey S Singer Jan H Smit Dan J Stein E Strengman Jay A Tischfield Ana V Valencia Duarte Homero Vallada Filip Van Nieuwerburgh Jeremy Veenstra-Vanderweele Susanne Walitza Ying Wang Jens R Wendland Herman G M Westenberg Yin Yao Shugart Euripedes C Miguel William McMahon Michael Wagner Humberto Nicolini Danielle Posthuma Gregory L Hanna Peter Heutink Damiaan Denys Paul D Arnold Ben A Oostra Gerald Nestadt Nelson B Freimer David L Pauls Naomi R Wray S Evelyn Stewart Carol A Mathews James A Knowles Nancy J Cox Jeremiah M Scharf |
| author_facet | Lea K Davis Dongmei Yu Clare L Keenan Eric R Gamazon Anuar I Konkashbaev Eske M Derks Benjamin M Neale Jian Yang S Hong Lee Patrick Evans Cathy L Barr Laura Bellodi Fortu Benarroch Gabriel Bedoya Berrio Oscar J Bienvenu Michael H Bloch Rianne M Blom Ruth D Bruun Cathy L Budman Beatriz Camarena Desmond Campbell Carolina Cappi Julio C Cardona Silgado Danielle C Cath Maria C Cavallini Denise A Chavira Sylvain Chouinard David V Conti Edwin H Cook Vladimir Coric Bernadette A Cullen Dieter Deforce Richard Delorme Yves Dion Christopher K Edlund Karin Egberts Peter Falkai Thomas V Fernandez Patience J Gallagher Helena Garrido Daniel Geller Simon L Girard Hans J Grabe Marco A Grados Benjamin D Greenberg Varda Gross-Tsur Stephen Haddad Gary A Heiman Sian M J Hemmings Ana G Hounie Cornelia Illmann Joseph Jankovic Michael A Jenike James L Kennedy Robert A King Barbara Kremeyer Roger Kurlan Nuria Lanzagorta Marion Leboyer James F Leckman Leonhard Lennertz Chunyu Liu Christine Lochner Thomas L Lowe Fabio Macciardi James T McCracken Lauren M McGrath Sandra C Mesa Restrepo Rainald Moessner Jubel Morgan Heike Muller Dennis L Murphy Allan L Naarden William Cornejo Ochoa Roel A Ophoff Lisa Osiecki Andrew J Pakstis Michele T Pato Carlos N Pato John Piacentini Christopher Pittenger Yehuda Pollak Scott L Rauch Tobias J Renner Victor I Reus Margaret A Richter Mark A Riddle Mary M Robertson Roxana Romero Maria C Rosàrio David Rosenberg Guy A Rouleau Stephan Ruhrmann Andres Ruiz-Linares Aline S Sampaio Jack Samuels Paul Sandor Brooke Sheppard Harvey S Singer Jan H Smit Dan J Stein E Strengman Jay A Tischfield Ana V Valencia Duarte Homero Vallada Filip Van Nieuwerburgh Jeremy Veenstra-Vanderweele Susanne Walitza Ying Wang Jens R Wendland Herman G M Westenberg Yin Yao Shugart Euripedes C Miguel William McMahon Michael Wagner Humberto Nicolini Danielle Posthuma Gregory L Hanna Peter Heutink Damiaan Denys Paul D Arnold Ben A Oostra Gerald Nestadt Nelson B Freimer David L Pauls Naomi R Wray S Evelyn Stewart Carol A Mathews James A Knowles Nancy J Cox Jeremiah M Scharf |
| author_sort | Lea K Davis |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-dcefb124869a49fdb60299acf97e56f6 |
| institution | OA Journals |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2013-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-dcefb124869a49fdb60299acf97e56f62025-08-20T02:22:49ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042013-10-01910e100386410.1371/journal.pgen.1003864Partitioning the heritability of Tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture.Lea K DavisDongmei YuClare L KeenanEric R GamazonAnuar I KonkashbaevEske M DerksBenjamin M NealeJian YangS Hong LeePatrick EvansCathy L BarrLaura BellodiFortu BenarrochGabriel Bedoya BerrioOscar J BienvenuMichael H BlochRianne M BlomRuth D BruunCathy L BudmanBeatriz CamarenaDesmond CampbellCarolina CappiJulio C Cardona SilgadoDanielle C CathMaria C CavalliniDenise A ChaviraSylvain ChouinardDavid V ContiEdwin H CookVladimir CoricBernadette A CullenDieter DeforceRichard DelormeYves DionChristopher K EdlundKarin EgbertsPeter FalkaiThomas V FernandezPatience J GallagherHelena GarridoDaniel GellerSimon L GirardHans J GrabeMarco A GradosBenjamin D GreenbergVarda Gross-TsurStephen HaddadGary A HeimanSian M J HemmingsAna G HounieCornelia IllmannJoseph JankovicMichael A JenikeJames L KennedyRobert A KingBarbara KremeyerRoger KurlanNuria LanzagortaMarion LeboyerJames F LeckmanLeonhard LennertzChunyu LiuChristine LochnerThomas L LoweFabio MacciardiJames T McCrackenLauren M McGrathSandra C Mesa RestrepoRainald MoessnerJubel MorganHeike MullerDennis L MurphyAllan L NaardenWilliam Cornejo OchoaRoel A OphoffLisa OsieckiAndrew J PakstisMichele T PatoCarlos N PatoJohn PiacentiniChristopher PittengerYehuda PollakScott L RauchTobias J RennerVictor I ReusMargaret A RichterMark A RiddleMary M RobertsonRoxana RomeroMaria C RosàrioDavid RosenbergGuy A RouleauStephan RuhrmannAndres Ruiz-LinaresAline S SampaioJack SamuelsPaul SandorBrooke SheppardHarvey S SingerJan H SmitDan J SteinE StrengmanJay A TischfieldAna V Valencia DuarteHomero ValladaFilip Van NieuwerburghJeremy Veenstra-VanderweeleSusanne WalitzaYing WangJens R WendlandHerman G M WestenbergYin Yao ShugartEuripedes C MiguelWilliam McMahonMichael WagnerHumberto NicoliniDanielle PosthumaGregory L HannaPeter HeutinkDamiaan DenysPaul D ArnoldBen A OostraGerald NestadtNelson B FreimerDavid L PaulsNaomi R WrayS Evelyn StewartCarol A MathewsJames A KnowlesNancy J CoxJeremiah M ScharfThe 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.https://doi.org/10.1371/journal.pgen.1003864 |
| spellingShingle | Lea K Davis Dongmei Yu Clare L Keenan Eric R Gamazon Anuar I Konkashbaev Eske M Derks Benjamin M Neale Jian Yang S Hong Lee Patrick Evans Cathy L Barr Laura Bellodi Fortu Benarroch Gabriel Bedoya Berrio Oscar J Bienvenu Michael H Bloch Rianne M Blom Ruth D Bruun Cathy L Budman Beatriz Camarena Desmond Campbell Carolina Cappi Julio C Cardona Silgado Danielle C Cath Maria C Cavallini Denise A Chavira Sylvain Chouinard David V Conti Edwin H Cook Vladimir Coric Bernadette A Cullen Dieter Deforce Richard Delorme Yves Dion Christopher K Edlund Karin Egberts Peter Falkai Thomas V Fernandez Patience J Gallagher Helena Garrido Daniel Geller Simon L Girard Hans J Grabe Marco A Grados Benjamin D Greenberg Varda Gross-Tsur Stephen Haddad Gary A Heiman Sian M J Hemmings Ana G Hounie Cornelia Illmann Joseph Jankovic Michael A Jenike James L Kennedy Robert A King Barbara Kremeyer Roger Kurlan Nuria Lanzagorta Marion Leboyer James F Leckman Leonhard Lennertz Chunyu Liu Christine Lochner Thomas L Lowe Fabio Macciardi James T McCracken Lauren M McGrath Sandra C Mesa Restrepo Rainald Moessner Jubel Morgan Heike Muller Dennis L Murphy Allan L Naarden William Cornejo Ochoa Roel A Ophoff Lisa Osiecki Andrew J Pakstis Michele T Pato Carlos N Pato John Piacentini Christopher Pittenger Yehuda Pollak Scott L Rauch Tobias J Renner Victor I Reus Margaret A Richter Mark A Riddle Mary M Robertson Roxana Romero Maria C Rosàrio David Rosenberg Guy A Rouleau Stephan Ruhrmann Andres Ruiz-Linares Aline S Sampaio Jack Samuels Paul Sandor Brooke Sheppard Harvey S Singer Jan H Smit Dan J Stein E Strengman Jay A Tischfield Ana V Valencia Duarte Homero Vallada Filip Van Nieuwerburgh Jeremy Veenstra-Vanderweele Susanne Walitza Ying Wang Jens R Wendland Herman G M Westenberg Yin Yao Shugart Euripedes C Miguel William McMahon Michael Wagner Humberto Nicolini Danielle Posthuma Gregory L Hanna Peter Heutink Damiaan Denys Paul D Arnold Ben A Oostra Gerald Nestadt Nelson B Freimer David L Pauls Naomi R Wray S Evelyn Stewart Carol A Mathews James A Knowles Nancy J Cox Jeremiah M Scharf Partitioning the heritability of Tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture. PLoS Genetics |
| title | 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_short | 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 |
| url | https://doi.org/10.1371/journal.pgen.1003864 |
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partitioningtheheritabilityoftourettesyndromeandobsessivecompulsivedisorderrevealsdifferencesingeneticarchitecture AT janhsmit partitioningtheheritabilityoftourettesyndromeandobsessivecompulsivedisorderrevealsdifferencesingeneticarchitecture AT danjstein partitioningtheheritabilityoftourettesyndromeandobsessivecompulsivedisorderrevealsdifferencesingeneticarchitecture AT estrengman partitioningtheheritabilityoftourettesyndromeandobsessivecompulsivedisorderrevealsdifferencesingeneticarchitecture AT jayatischfield partitioningtheheritabilityoftourettesyndromeandobsessivecompulsivedisorderrevealsdifferencesingeneticarchitecture AT anavvalenciaduarte partitioningtheheritabilityoftourettesyndromeandobsessivecompulsivedisorderrevealsdifferencesingeneticarchitecture AT homerovallada partitioningtheheritabilityoftourettesyndromeandobsessivecompulsivedisorderrevealsdifferencesingeneticarchitecture AT filipvannieuwerburgh partitioningtheheritabilityoftourettesyndromeandobsessivecompulsivedisorderrevealsdifferencesingeneticarchitecture AT jeremyveenstravanderweele partitioningtheheritabilityoftourettesyndromeandobsessivecompulsivedisorderrevealsdifferencesingeneticarchitecture AT susannewalitza partitioningtheheritabilityoftourettesyndromeandobsessivecompulsivedisorderrevealsdifferencesingeneticarchitecture AT yingwang partitioningtheheritabilityoftourettesyndromeandobsessivecompulsivedisorderrevealsdifferencesingeneticarchitecture AT jensrwendland partitioningtheheritabilityoftourettesyndromeandobsessivecompulsivedisorderrevealsdifferencesingeneticarchitecture AT hermangmwestenberg partitioningtheheritabilityoftourettesyndromeandobsessivecompulsivedisorderrevealsdifferencesingeneticarchitecture AT yinyaoshugart partitioningtheheritabilityoftourettesyndromeandobsessivecompulsivedisorderrevealsdifferencesingeneticarchitecture AT euripedescmiguel partitioningtheheritabilityoftourettesyndromeandobsessivecompulsivedisorderrevealsdifferencesingeneticarchitecture AT williammcmahon partitioningtheheritabilityoftourettesyndromeandobsessivecompulsivedisorderrevealsdifferencesingeneticarchitecture AT michaelwagner partitioningtheheritabilityoftourettesyndromeandobsessivecompulsivedisorderrevealsdifferencesingeneticarchitecture AT humbertonicolini partitioningtheheritabilityoftourettesyndromeandobsessivecompulsivedisorderrevealsdifferencesingeneticarchitecture AT danielleposthuma partitioningtheheritabilityoftourettesyndromeandobsessivecompulsivedisorderrevealsdifferencesingeneticarchitecture AT gregorylhanna partitioningtheheritabilityoftourettesyndromeandobsessivecompulsivedisorderrevealsdifferencesingeneticarchitecture AT peterheutink partitioningtheheritabilityoftourettesyndromeandobsessivecompulsivedisorderrevealsdifferencesingeneticarchitecture AT damiaandenys partitioningtheheritabilityoftourettesyndromeandobsessivecompulsivedisorderrevealsdifferencesingeneticarchitecture AT pauldarnold partitioningtheheritabilityoftourettesyndromeandobsessivecompulsivedisorderrevealsdifferencesingeneticarchitecture AT benaoostra partitioningtheheritabilityoftourettesyndromeandobsessivecompulsivedisorderrevealsdifferencesingeneticarchitecture AT geraldnestadt partitioningtheheritabilityoftourettesyndromeandobsessivecompulsivedisorderrevealsdifferencesingeneticarchitecture AT nelsonbfreimer partitioningtheheritabilityoftourettesyndromeandobsessivecompulsivedisorderrevealsdifferencesingeneticarchitecture AT davidlpauls partitioningtheheritabilityoftourettesyndromeandobsessivecompulsivedisorderrevealsdifferencesingeneticarchitecture AT naomirwray partitioningtheheritabilityoftourettesyndromeandobsessivecompulsivedisorderrevealsdifferencesingeneticarchitecture AT sevelynstewart partitioningtheheritabilityoftourettesyndromeandobsessivecompulsivedisorderrevealsdifferencesingeneticarchitecture AT carolamathews partitioningtheheritabilityoftourettesyndromeandobsessivecompulsivedisorderrevealsdifferencesingeneticarchitecture AT jamesaknowles partitioningtheheritabilityoftourettesyndromeandobsessivecompulsivedisorderrevealsdifferencesingeneticarchitecture AT nancyjcox partitioningtheheritabilityoftourettesyndromeandobsessivecompulsivedisorderrevealsdifferencesingeneticarchitecture AT jeremiahmscharf partitioningtheheritabilityoftourettesyndromeandobsessivecompulsivedisorderrevealsdifferencesingeneticarchitecture |