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Título : | Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture |
Autor : | Davis, Lea Yu, Dongmei Keenan, Clare Gamazon, Eric Konkashbaev, Anuar Derks, Eske Neale, Benjamin Yang, Jian Lee, S. Hong Evans, Patrick Barr, Cathy Strengman, E. Tischfield, Jay Valencia Duarte, Ana Victoria Vallada, Homero Van Nieuwerburgh, Filip Veenstra VanderWeele, Jeremy Walitza, Susanne Wang, Ying Wendland, Jens Westenberg, Herman Bellodi, Laura Shugart, Yin Yao Miguel, Euripedes McMahon, William Wagner, Michael Nicolini, Humberto Posthuma, Danielle Hanna, Gregory Heutink, Peter Denys, Damiaan Arnold, Paul Benarroch, Fortu Oostra, Ben Nestadt, Gerald Freimer, Nelson Pauls, David Wray, Naomi Stewart, Evelyn Mathews, Carol Knowles, James Cox, Nancy Scharf, Jeremiah Bedoya Berrío, Gabriel de Jesús Bienvenu, Oscar Bloch, Michael Blom, Rianne Bruun, Ruth Budman, Cathy Camarena, Beatriz Cappi, Carolina Cardona Silgado, Julio Cesar Cath, Danielle Cavallini, Maria Chavira, Denise Chouinard, Sylvain Conti, David Cook, Edwin Coric, Vladimir Cullen, Bernadette Deforce, Dieter Delorme, Richard Dion, Yves Edlund, Christopher Egberts, Karin Falkai, Peter Fernández, Thomas Gallagher, Patience Garrido, Helena Geller, Daniel Girard, Simon Grabe, Hans Grados, Marco Greenberg, Benjamin Gross-Tsur, Varda Haddad, Stephen Heiman, Gary Hemmings, Sian Hounie, Ana Illmann, Cornelia Jankovic, Joseph Jenike, Michael Kennedy, James King, Robert Kremeyer, Barbara Kurlan, Roger Lanzagorta, Nuria Leboyer, Marion Leckman, James Lennertz, Leonhard Liu, Chunyu Lochner, Christine Lowe, Thomas Macciardi, Fabio McCracken, James McGrath, Lauren Mesa Restrepo, Sandra Catalina Moessner, Rainald Morgan, Jubel Muller, Heike Murphy, Dennis Naarden, Allan Cornejo Ochoa, José William Ophoff, Roel Osiecki, Lisa Pakstis, Andrew Pato, Michele Pato, Carlos Piacentini, John Pittenger, Christopher Pollak, Yehuda Rauch, Scott Renner, Tobias Reus, Victor Richter, Margaret Riddle, Mark Robertson, Mary Romero, Roxana Rosario, Maria Rosenberg, David Rouleau, Guy Ruhrmann, Stephan Ruíz Linares, Andrés Sampaio, Aline Samuels, Jack Sandor, Paul Sheppard, Brooke Singer, Harvey Smit, Jan Stein, Dan |
metadata.dc.subject.*: | Síndrome de Tourette Tourette Syndrome Trastorno Obsesivo Compulsivo Obsessive-Compulsive Disorder |
Fecha de publicación : | 2013 |
Editorial : | Public Library of Science |
Citación : | Davis LK, Yu D, Keenan CL, Gamazon ER, Konkashbaev AI, et al. (2013) Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture. PLoS Genet 9(10): e1003864. doi:10.1371/journal.pgen.1003864 |
Resumen : | 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. |
metadata.dc.identifier.eissn: | 1553-7404 |
ISSN : | 1553-7390 |
metadata.dc.identifier.doi: | 10.1371/journal.pgen.1003864 |
Aparece en las colecciones: | Artículos de Revista en Ciencias Exactas y Naturales |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
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BedoyaGabriel_2013_HeritabilityTouretteSyndrome.pdf | Artículo de investigación | 637.3 kB | Adobe PDF | Visualizar/Abrir |
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