Partitioning the heritability of Tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture
Date
2013-10
Journal Title
Journal ISSN
Volume Title
Publisher
PLoS
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.
Description
CITATION: Davis, L.K. et al. 2013. Partitioning the heritability of Tourette Syndrome and
obsessive compulsive disorder reveals differences in
genetic architecture. PLoS Genetics, 9(10):e1003864, doi:10.1371/journal.pgen.1003864.
The original publication is available at http://journals.plos.org/plosgenetics
The original publication is available at http://journals.plos.org/plosgenetics
Keywords
Tourette syndrome -- Genetic aspects, Obsessive-compulsive disorder -- Genetic aspects
Citation
Davis, L.K. et al. 2013. Partitioning the heritability of Tourette Syndrome and
obsessive compulsive disorder reveals differences in
genetic architecture. PLoS Genetics, 9(10):e1003864, doi:10.1371/journal.pgen.1003864.