Rare Copy Number Variants in NRXN1 and CNTN6 Increase Risk for Tourette Syndrome
| Title: | Rare Copy Number Variants in NRXN1 and CNTN6 Increase Risk for Tourette Syndrome |
|---|---|
| Authors: | Huang AY; Yu D; Davis LK; Sul JH; Tsetsos F; Ramensky V; Zelaya I; Ramos EM; Osiecki L; Chen JA; McGrath LM; Illmann C; Sandor P; Barr CL; Grados M; Singer HS; Nothen MM; Hebebrand J; King RA; Dion Y; Rouleau G; Budman CL; Depienne C; Worbe Y; Hartmann A; Muller-Vahl KR; Stuhrmann M; Aschauer H; Stamenkovic M; Schloegelhofer M; Konstantinidis A; Lyon GJ; McMahon WM; Barta, Csaba; Tárnok, Zsanett; Nagy, Péter; Batterson JR; Rizzo R; Cath DC; Wolanczyk T; Berlin C; Malaty IA; Okun MS; Woods DW; Rees E; Pato CN; Pato MT; Knowles JA; Posthuma D; Pauls DL; Cox NJ; Neale BM; Freimer NB; Paschou P; Mathews CA; Scharf JM; Coppola G; Tourette Syndrome Association International Consortium for Genetics (TSAICG); Gilles de la Tourette Syndrome GWAS Replication Initiative (GGRI) |
| Contributors: | SE/AOK/I/Orvosi Vegytani, Molekuláris Biológiai és Patobiokémiai Intézet; Semmelweis Egyetem |
| Publication Year: | 2017 |
| Collection: | Semmelweis Egyetem: Repozitórium |
| Description: | Tourette syndrome (TS) is a model neuropsychiatric disorder thought to arise from abnormal development and/or maintenance of cortico-striato-thalamo-cortical circuits. TS is highly heritable, but its underlying genetic causes are still elusive, and no genome-wide significant loci have been discovered to date. We analyzed a European ancestry sample of 2,434 TS cases and 4,093 ancestry-matched controls for rare (< 1% frequency) copy-number variants (CNVs) using SNP microarray data. We observed an enrichment of global CNV burden that was prominent for large (> 1 Mb), singleton events (OR = 2.28, 95% CI [1.39-3.79], p = 1.2 x 10-3) and known, pathogenic CNVs (OR = 3.03 [1.85-5.07], p = 1.5 x 10-5). We also identified two individual, genome-wide significant loci, each conferring a substantial increase in TS risk (NRXN1 deletions, OR = 20.3, 95% CI [2.6-156.2]; CNTN6 duplications, OR = 10.1, 95% CI [2.3-45.4]). Approximately 1% of TS cases carry one of these CNVs, indicating that rare structural variation contributes significantly to the genetic architecture of TS. |
| Document Type: | article in journal/newspaper |
| Language: | English |
| ISSN: | 0896-6273 |
| Relation: | urn:issn:0896-6273; http://repo.lib.semmelweis.hu//handle/123456789/6793; 3249806; 000403820200009 |
| DOI: | 10.1016/j.neuron.2017.06.010 |
| Availability: | http://repo.lib.semmelweis.hu//handle/123456789/6793; https://doi.org/10.1016/j.neuron.2017.06.010 |
| Rights: | NULL |
| Accession Number: | edsbas.BE82C63D |
| Database: | BASE |