Please use this identifier to cite or link to this item: http://repositorio.unifesp.br/handle/11600/36782
Title: Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture
Authors: 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
Silgado, Julio C. Cardona
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
Falkai, 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.
Restrepo, Sandra C. Mesa
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. [UNIFESP]
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.
Duarte, Ana V. Valencia
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.
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Issue Date: 1-Oct-2013
Publisher: Public Library Science
Citation: Plos Genetics. San Francisco: Public Library Science, v. 9, n. 10, 14 p., 2013.
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.
URI: http://repositorio.unifesp.br/handle/11600/36782
ISSN: 1553-7404
Other Identifiers: http://dx.doi.org/10.1371/journal.pgen.1003864
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