| Title: |
Rare Copy Number Variants in NRXN1 and CNTN6 Increase Risk for Tourette Syndrome |
| Authors: |
Huang, Alden Y.; Yu, Dongmei; Davis, Lea K.; Sul, Jae Hoon; Tsetsos, Fotis; Ramensky, Vasily; Zelaya, Ivette; Ramos, Eliana Marisa; Osiecki, Lisa; Chen, Jason A.; McGrath, Lauren M.; Illmann, Cornelia; Sandor, Paul; Barr, Cathy L.; Grados, Marco; Singer, Harvey S.; Nöthen, Marcus M.; Hebebrand, Johannes; King, Robert A.; Dion, Yves; Rouleau, Guy; Budman, Cathy L.; Depienne, Christel; Worbe, Yulia; Hartmenn, Andreas; Müller-Vahl, Kirsten R.; Stuhrmann, Manfred; Aschauer, Harald; Stamenkovic, Mara; Schloegelhofer, Monika; Konstantinidis, Anastasios; Lyon, Gholson J.; McMahon, William M.; Barta, Csaba; Tarnok, Zsanett; Nagy, Peter; Batterson, James R.; Rizzo, Renata; Cath, Danielle C.; Wolanczyk, Tomasz; Berlin, Cheston; Malaty, Irene A.; Okun, Michael S.; Woods, Douglas W.; Rees, Elliott; Pato, Carlos N.; Pato, Michele T.; Knowles, James A.; Posthuma, Danielle; Pauls, David L.; Cox, Nancy J.; Neale, Benjamin M.; Freimer, Nelson B.; Paschou, Peristera; Mathews, Carol A.; Scharf, Jeremiah M.; Coppola, Giovanni |
| Source: |
Psychology Faculty Research and Publications |
| Publisher Information: |
e-Publications@Marquette |
| Publication Year: |
2017 |
| Collection: |
Marquette University: e-Publications@Marquette |
| Subject Terms: |
Tourette Syndrome; tic disorders; neurodevelopmental disorders; genetics; structural variation; copy number variation; NRXN1; CNTN6; Psychology |
| 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 × 10−3) and known, pathogenic CNVs (OR = 3.03 [1.85–5.07], p = 1.5 × 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: |
text |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://epublications.marquette.edu/psych_fac/288; https://epublications.marquette.edu/context/psych_fac/article/1298/viewcontent/woods_10710.pdf |
| Availability: |
https://epublications.marquette.edu/psych_fac/288; https://epublications.marquette.edu/context/psych_fac/article/1298/viewcontent/woods_10710.pdf |
| Accession Number: |
edsbas.1F8D4E93 |
| Database: |
BASE |