Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture

Davis, Lea K., Yu, Dongmei, Keenan, Clare L., Gamazon, Eric R., Konkashbaev, Anuar I., Derks, Eske M., Neale, Benjamin M., Yang, Jian, Lee, S. Hong, Evans, Patrick, Barr, Cathy L., Bellodi, Laura, Benarroch, Fortu, Berrio, Gabriel Bedoya, Bienvenu, Oscar J., Bloch, Michael H., Blom, Rianne M., Bruun, Ruth D., Budman, Cathy L., Camarena, Beatriz, Campbell, Desmond, Cappi, Carolina, Cardona Silgado, Julio C., Cath, Danielle C., Cavallini, Maria C., Chavira, Denise A., Chouinard, Sylvain, Conti, David V, Cook, Edwin H, Coric, Vladimir, Cullen, Bernadette A., Deforce, Dieter, Delorme, Richard, Dion, Yves, Edlund, Christopher K., Egberts, Karin, Falka, Peter, Fernandez, Thomas V., Gallagher, Patience J., Garrido, Helena, Geller, Daniel, Girard, Simon L, Grabe, Hans J., Grados, Marco A., Greenberg, Benjamin D., Gross-Tsur, Varda, Haddad, Stephen, Heiman, Gary A., Hemmings, Sian M. J., Hounie, Ana G., Illmann, Cornelia, Jankovic, Joseph, Jenike, Michael A., Kennedy, James L., King, Robert A., Kremeyer, Barbara, Kurlan, Roger, Lanzagorta, Nuria, Leboyer, Marion, Leckman, James F, Lennertz, Leonhard, Liu, , Chunyu, Lochner, Christine, Lowe, Thomas L., Macciardi,Fabio, McCracken, James T., McGrath, Lauren M., Mesa Restrepo, Sandra C., Moessner, Rainald, Morgan, Jubel, Muller, Heike, Murphy, Dennis L., Naarden, Allan L., Ochoa, William Cornejo, Ophoff, Roel A., Osiecki, Lisa, Pakstis, Andrew J., Pato, , Michele T., Pato, Carlos N., Piacentini, John, Pittenger, Christopher, Pollak, Yehuda, Rauch, Scott L., Renner, Tobias J., Reus, Victor I., Richter, Margaret A., Riddle, Mark A., Robertson, Mary M., Romero, Roxana, Rosario, Maria C., Rosenberg, David, Rouleau, , Guy A., Ruhrmann, Stephan, Ruiz-Linares, Andres, Sampaio, Aline S., Samuels, Jack, Sandor, Paul, Sheppard, Brooke, Singer, Harvey S., Smit, Jan H., Stein, Dan J, Strengman, E., Tischfield, Jay A., Valencia Duarte, Ana V., Vallada, Homero, Van Nieuwerburgh, Filip, Veenstra-VanderWeele, Jeremy, Walitza, Susanne, Wang, Ying, Wendland, Jens R., Westenberg, Herman G. M., Shugart, Yin Yao, Miguel,Euripedes C., McMahon, William, Wagner, Michael, Nicolini, Humberto, Posthuma, Danielle, Hanna, Gregory L., Heutink, Peter, Denys, Damiaan, Arnold, Paul D., Oostra, Ben A., Nestadt, Gerald, Freimer, Nelson B., Pauls, David L., Wray, Naomi R., Stewart, S. Evelyn, Mathews, Carol A., Knowles, James A., Cox, Nancy J. and Scharf, Jeremiah M. (2013) Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture. PLoS Genetics, 9 10: e1003864.1-e1003864.14. doi:10.1371/journal.pgen.1003864


Author Davis, Lea K.
Yu, Dongmei
Keenan, Clare L.
Gamazon, Eric R.
Konkashbaev, Anuar I.
Derks, Eske M.
Neale, Benjamin M.
Yang, Jian
Lee, S. Hong
Evans, Patrick
Barr, Cathy L.
Bellodi, Laura
Benarroch, Fortu
Berrio, Gabriel Bedoya
Bienvenu, Oscar J.
Bloch, Michael H.
Blom, Rianne M.
Bruun, Ruth D.
Budman, Cathy L.
Camarena, Beatriz
Campbell, Desmond
Cappi, Carolina
Cardona Silgado, Julio C.
Cath, Danielle C.
Cavallini, Maria C.
Chavira, Denise A.
Chouinard, Sylvain
Conti, David V
Cook, Edwin H
Coric, Vladimir
Cullen, Bernadette A.
Deforce, Dieter
Delorme, Richard
Dion, Yves
Edlund, Christopher K.
Egberts, Karin
Falka, Peter
Fernandez, Thomas V.
Gallagher, Patience J.
Garrido, Helena
Geller, Daniel
Girard, Simon L
Grabe, Hans J.
Grados, Marco A.
Greenberg, Benjamin D.
Gross-Tsur, Varda
Haddad, Stephen
Heiman, Gary A.
Hemmings, Sian M. J.
Hounie, Ana G.
Illmann, Cornelia
Jankovic, Joseph
Jenike, Michael A.
Kennedy, James L.
King, Robert A.
Kremeyer, Barbara
Kurlan, Roger
Lanzagorta, Nuria
Leboyer, Marion
Leckman, James F
Lennertz, Leonhard
Liu, , Chunyu
Lochner, Christine
Lowe, Thomas L.
Macciardi,Fabio
McCracken, James T.
McGrath, Lauren M.
Mesa Restrepo, Sandra C.
Moessner, Rainald
Morgan, Jubel
Muller, Heike
Murphy, Dennis L.
Naarden, Allan L.
Ochoa, William Cornejo
Ophoff, Roel A.
Osiecki, Lisa
Pakstis, Andrew J.
Pato, , Michele T.
Pato, Carlos N.
Piacentini, John
Pittenger, Christopher
Pollak, Yehuda
Rauch, Scott L.
Renner, Tobias J.
Reus, Victor I.
Richter, Margaret A.
Riddle, Mark A.
Robertson, Mary M.
Romero, Roxana
Rosario, Maria C.
Rosenberg, David
Rouleau, , Guy A.
Ruhrmann, Stephan
Ruiz-Linares, Andres
Sampaio, Aline S.
Samuels, Jack
Sandor, Paul
Sheppard, Brooke
Singer, Harvey S.
Smit, Jan H.
Stein, Dan J
Strengman, E.
Tischfield, Jay A.
Valencia Duarte, Ana V.
Vallada, Homero
Van Nieuwerburgh, Filip
Veenstra-VanderWeele, Jeremy
Walitza, Susanne
Wang, Ying
Wendland, Jens R.
Westenberg, Herman G. M.
Shugart, Yin Yao
Miguel,Euripedes C.
McMahon, William
Wagner, Michael
Nicolini, Humberto
Posthuma, Danielle
Hanna, Gregory L.
Heutink, Peter
Denys, Damiaan
Arnold, Paul D.
Oostra, Ben A.
Nestadt, Gerald
Freimer, Nelson B.
Pauls, David L.
Wray, Naomi R.
Stewart, S. Evelyn
Mathews, Carol A.
Knowles, James A.
Cox, Nancy J.
Scharf, Jeremiah M.
Title Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture
Journal name PLoS Genetics   Check publisher's open access policy
ISSN 1553-7390
Publication date 2013-01-01
Year available 2013
Sub-type Article (original research)
DOI 10.1371/journal.pgen.1003864
Open Access Status DOI
Volume 9
Issue 10
Start page e1003864.1
End page e1003864.14
Total pages 14
Place of publication San Francisco, CA United States
Publisher Public Library of Science
Language eng
Subject 1311 Genetics
1312 Molecular Biology
1105 Dentistry
1306 Cancer Research
2716 Genetics (clinical)
Abstract 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.
Keyword Genetics & Heredity
Genetics & Heredity
GENETICS & HEREDITY
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID NS40024
R01MH092293
NS40024-07S1
FT0991360
1047956
DFG GR 1912/1-1
U01 HG004422
U01HG004438
R01 MH090937
P50MH094267
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2014 Collection
UQ Diamantina Institute Publications
 
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