Journal article
Concordance of genetic variation that increases risk for tourette syndrome and that influences its underlying neurocircuitry
Translational psychiatry, Vol.9(1), pp.120-120
03/22/2019
DOI: 10.1038/s41398-019-0452-3
PMCID: PMC6430767
PMID: 30902966
Abstract
There have been considerable recent advances in understanding the genetic architecture of Tourette syndrome (TS) as well as its underlying neurocircuitry. However, the mechanisms by which genetic variation that increases risk for TS-and its main symptom dimensions-influence relevant brain regions are poorly understood. Here we undertook a genome-wide investigation of the overlap between TS genetic risk and genetic influences on the volume of specific subcortical brain structures that have been implicated in TS. We obtained summary statistics for the most recent TS genome-wide association study (GWAS) from the TS Psychiatric Genomics Consortium Working Group (4644 cases and 8695 controls) and GWAS of subcortical volumes from the ENIGMA consortium (30,717 individuals). We also undertook analyses using GWAS summary statistics of key symptom factors in TS, namely social disinhibition and symmetry behaviour. SNP effect concordance analysis (SECA) was used to examine genetic pleiotropy-the same SNP affecting two traits-and concordance-the agreement in single nucelotide polymorphism (SNP) effect directions across these two traits. In addition, a conditional false discovery rate (FDR) analysis was performed, conditioning the TS risk variants on each of the seven subcortical and the intracranial brain volume GWAS. Linkage disequilibrium score regression (LDSR) was used as validation of the SECA method. SECA revealed significant pleiotropy between TS and putamen (p = 2 × 10
) and caudate (p = 4 × 10
) volumes, independent of direction of effect, and significant concordance between TS and lower thalamic volume (p = 1 × 10
). LDSR lent additional support for the association between TS and thalamus volume (p = 5.85 × 10
). Furthermore, SECA revealed significant evidence of concordance between the social disinhibition symptom dimension and lower thalamus volume (p = 1 × 10
), as well as concordance between symmetry behaviour and greater putamen volume (p = 7 × 10
). Conditional FDR analysis further revealed novel variants significantly associated with TS (p < 8 × 10
) when conditioning on intracranial (rs2708146, q = 0.046; and rs72853320, q = 0.035) and hippocampal (rs1922786, q = 0.001) volumes, respectively. These data indicate concordance for genetic variation involved in disorder risk and subcortical brain volumes in TS. Further work with larger samples is needed to fully delineate the genetic architecture of these disorders and their underlying neurocircuitry.
Details
- Title: Subtitle
- Concordance of genetic variation that increases risk for tourette syndrome and that influences its underlying neurocircuitry
- Creators
- Mary Mufford - University of Cape TownJosh Cheung - University of Southern CaliforniaNeda Jahanshad - University of Southern CaliforniaCelia van der Merwe - University of Cape TownLinda Ding - University of Southern CaliforniaNynke Groenewold - University of Cape TownNastassja Koen - University of Cape TownEmile R Chimusa - University of Cape TownShareefa Dalvie - University of Cape TownRaj Ramesar - University of Cape TownJames A Knowles - Zilkha Neurogenetic InstituteChristine Lochner - Stellenbosch UniversityDerrek P Hibar - University of Southern CaliforniaPeristera Paschou - Purdue University West LafayetteOdile A van den Heuvel - Amsterdam NeuroscienceSarah E Medland - QIMR Berghofer Medical Research InstituteJeremiah M Scharf - Harvard Medical SchoolCarol A Mathews - University of FloridaPaul M Thompson - University of Southern CaliforniaDan J Stein - University of Cape TownPsychiatric Genomics Consortium - Tourette Syndrome working group
- Contributors
- Samuel Kuperman (Contributor) - University of Iowa, Psychiatry
- Resource Type
- Journal article
- Publication Details
- Translational psychiatry, Vol.9(1), pp.120-120
- DOI
- 10.1038/s41398-019-0452-3
- PMID
- 30902966
- PMCID
- PMC6430767
- NLM abbreviation
- Transl Psychiatry
- ISSN
- 2158-3188
- eISSN
- 2158-3188
- Grant note
- R01 MH092293 / NIMH NIH HHS R01 NS102371 / NINDS NIH HHS R01 NS016648 / NINDS NIH HHS U54 EB020403 / NIBIB NIH HHS U01 MH109536 / NIMH NIH HHS R01 MH092513 / NIMH NIH HHS R01 MH092290 / NIMH NIH HHS R01 MH092291 / NIMH NIH HHS R01 MH092520 / NIMH NIH HHS R01 MH115961 / NIMH NIH HHS U24 MH068457 / NIMH NIH HHS R01 MH092516 / NIMH NIH HHS R01 NS105746 / NINDS NIH HHS U01 NS040024 / NINDS NIH HHS R01 MH092289 / NIMH NIH HHS R01 MH115958 / NIMH NIH HHS R01 MH092292 / NIMH NIH HHS R01 NS040024 / NINDS NIH HHS
- Language
- English
- Date published
- 03/22/2019
- Academic Unit
- Psychiatry
- Record Identifier
- 9984293755302771
Metrics
14 Record Views