Advanced search
1 file | 652.59 KB

Partitioning the heritability of Tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture

(2013) PLOS GENETICS. 9(10).
Author
Organization
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.
Keywords
BRAIN, FAMILY, GILLES, COMMON SNPS, COMPLEX DISEASES, NEUROPSYCHIATRIC DISORDERS, TIC DISORDERS, MISSING HERITABILITY, EXPRESSION, AUTISM

Downloads

  • fetchObject.pdf
    • full text
    • |
    • open access
    • |
    • PDF
    • |
    • 652.59 KB

Citation

Please use this url to cite or link to this publication:

Chicago
Davis, Lea K, Dongmei Yu, Clare L Keenan, Eric R Gamazon, Anuar I Konkashbaev, Eske M Derks, Benjamin M Neale, et al. 2013. “Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture.” Plos Genetics 9 (10).
APA
Davis, L. K., Yu, D., Keenan, C. L., Gamazon, E. R., Konkashbaev, A. I., Derks, E. M., Neale, B. M., et al. (2013). Partitioning the heritability of Tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture. PLOS GENETICS, 9(10).
Vancouver
1.
Davis LK, Yu D, Keenan CL, Gamazon ER, Konkashbaev AI, Derks EM, et al. Partitioning the heritability of Tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture. PLOS GENETICS. 2013;9(10).
MLA
Davis, Lea K, Dongmei Yu, Clare L Keenan, et al. “Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture.” PLOS GENETICS 9.10 (2013): n. pag. Print.
@article{4416402,
  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.},
  articleno    = {e1003864},
  author       = {Davis, Lea K and Yu, Dongmei and Keenan, Clare L and Gamazon, Eric R and Konkashbaev, Anuar I and Derks, Eske M and Neale, Benjamin M and Yang, Jian and Lee, S Hong and Evans, Patrick and Barr, Cathy L and Bellodi, Laura and Benarroch, Fortu and Berrio, Gabriel Bedoya and Bienvenu, Oscar J and Bloch, Michael H and Blom, Rianne M and Bruun, Ruth D and Budman, Cathy L and Camarena, Beatriz and Campbell, Desmond and Cappi, Carolina and Cardona Silgado, Julio C and Cath, Danielle C and Cavallini, Maria C and Chavira, Denise A and Chouinard, Sylvain and Conti, David V and Cook, Edwin H and Coric, Vladimir and Cullen, Bernadette A and Deforce, Dieter and Delorme, Richard and Dion, Yves and Edlund, Christopher K and Egberts, Karin and Falkai, Peter and Fernandez, Thomas V and Gallagher, Patience J and Garrido, Helena and Geller, Daniel and Girard, Simon L and Grabe, Hans J and Grados, Marco A and Greenberg, Benjamin D and Gross-Tsur, Varda and Haddad, Stephen and Heiman, Gary A and Hemmings, Sian MJ and Hounie, Ana G and Illmann, Cornelia and Jankovic, Joseph and Jenike, Michael A and Kennedy, James L and King, Robert A and Kremeyer, Barbara and Kurlan, Roger and Lanzagorta, Nuria and Leboyer, Marion and Leckman, James F and Lennertz, Leonhard and Liu, Chunyu and Lochner, Christine and Lowe, Thomas L and Macciardi, Fabio and McCracken, James T and McGrath, Lauren M and Mesa Restrepo, Sandra C and Moessner, Rainald and Morgan, Jubel and Muller, Heike and Murphy, Dennis L and Naarden, Allan L and Ochoa, William Cornejo and Ophoff, Roel A and Osiecki, Lisa and Pakstis, Andrew J and Pato, Michele T and Pato, Carlos N and Piacentini, John and Pittenger, Christopher and Pollak, Yehuda and Rauch, Scott L and Renner, Tobias J and Reus, Victor I and Richter, Margaret A and Riddle, Mark A and Robertson, Mary M and Romero, Roxana and Ros{\`a}rio, Maria C and Rosenberg, David and Rouleau, Guy A and Ruhrmann, Stephan and Ruiz-Linares, Andres and Sampaio, Aline S and Samuels, Jack and Sandor, Paul and Sheppard, Brooke and Singer, Harvey S and Smit, Jan H and Stein, Dan J and Strengman, E and Tischfield, Jay A and Valencia Duarte, Ana V and Vallada, Homero and Van Nieuwerburgh, Filip and Veenstra-VanderWeele, Jeremy and Walitza, Susanne and Wang, Ying and Wendland, Jens R and Westenberg, Herman GM and Shugart, Yin Yao and Miguel, Euripedes C and McMahon, William and Wagner, Michael and Nicolini, Humberto and Posthuma, Danielle and Hanna, Gregory L and Heutink, Peter and Denys, Damiaan and Arnold, Paul D and Oostra, Ben A and Nestadt, Gerald and Freimer, Nelson B and Pauls, David L and Wray, Naomi R and Stewart, S Evelyn and Mathews, Carol A and Knowles, James A and Cox, Nancy J and Scharf, Jeremiah M},
  issn         = {1553-7404},
  journal      = {PLOS GENETICS},
  language     = {eng},
  number       = {10},
  pages        = {14},
  title        = {Partitioning the heritability of Tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture},
  url          = {http://dx.doi.org/10.1371/journal.pgen.1003864},
  volume       = {9},
  year         = {2013},
}

Altmetric
View in Altmetric
Web of Science
Times cited: