Download Pathway Analysis on Genome-wide data for Tourette Syndrome

Pathway Analysis on Genome-wide data for Tourette Syndrome Shows Enrichment in Genes expressed in
Nervous System Tissues
Tsetsos F1*, Alexander J2, Yu D3, Sul J4, Coppola G5, Zelaya I6, Drineas P7, G8, T9, Mathews C10, Scharf J11,
Paschou P12
1*
Department of Molecular Biology and Genetics, Democritus University of thrace, Alexandroupolis, Evros,
Greece, [email protected]
2
Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis, Greece
3
Harvard Medical School, Massachusetts General Hospital, Boston, United States
4
Harvard Medical School, Boston, United States
5
University of California, Los Angeles, Los Angeles, United States
6
University of California, Los Angeles, United States
7
Rensselaer Polytechnic Institute, Troy, United States
8
GGRI, GGRI, Greece
9
TSAICG, TSAICG, United States
10
University of California, San Francisco, San Francisco, CA, United States
11
Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetics Research, Department of
Psychiatry, Harvard Medical School, Massachusetts General Hospital, Boston, MA, United States
12
Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupoli, Greece
INTRODUCTION AND OBJECTIVES
Gilles de la Tourette Syndrome is a childhood-onset neuropsychiatric disorder that is characterised by a multitude of
vocal and motor tics. Recent advances in the genetics of Gilles de la Tourette Syndrome are starting to shed new
light in its genetic aetiology. Yu et al. in 2015 report a second Genome Wide Association Study on Gilles de la
Tourette Syndrome on 2,859 cases/3,855 controls. Following meta-analysis with the first Genome Wide Association
Study (1,117 cases /4,955 controls) and the TIC Genetics Trios (184 cases/184 controls), they report multiple LDindependent SNPs with p-value less than 10-5. These SNPs implicate novel loci on Tourette Syndrome pathogenesis.
METHODS
We focused on the top scoring SNPs from the meta-analysis of the Genome Wide Association Study on Gilles de la
Tourette Syndrome for downstream pathway analysis. For the pathway analysis we used DEPICT, a novel tool for
the interpretation of GWAS results, and additional pathway analysis software, including MAGENTA and INRICH.
Furthermore, we also applied a set-based association approach on the Second Genome Wide Association Study case
and control data. In order to perform the set-based association, we collected pathway gene sets from KEGG,
REACTOME, Molecular Signatures Database, OMIM and we constructed sets of SNPs located at genes present on
the pathway gene sets.
RESULTS AND DISCUSSION
DEPICT analysis showed significant enrichment among top TS associated SNPs in genes expressed in nervous
system tissues, including the parietal lobe and the basal ganglia. We also report the results from the set based
association analysis, which further illuminate candidate pathways for investigation.
CONCLUSIONS
Our study aims to untangle the complex interaction networks of genes implicated in TS and points to candidate
etiological pathways for further investigation in future studies.
REFERENCES
1.Yu et al. Genome-wide association study in Tourette Syndrome implicates lncRNA in Tourette Syndrome
aetiology. In preparation
2.Pers et al. Biological interpretation of genome-wide association studies using predicted gene functions. Nat
Commun. 2015 Jan 19;6:5890