TY - JOUR
T1 - Rare Copy Number Variants in NRXN1 and CNTN6 Increase Risk for Tourette Syndrome
AU - The Tourette Syndrome Association International Consortium for Genetics (TSAICG)
AU - The Gilles de la Tourette Syndrome GWAS Replication Initiative (GGRI)
AU - The Gilles de la Tourette Syndrome GWAS Replication Initiative (GGRI)
AU - Huang, Alden Y.
AU - Yu, Dongmei
AU - Davis, Lea K.
AU - Sul, Jae Hoon
AU - Tsetsos, Fotis
AU - Ramensky, Vasily
AU - Zelaya, Ivette
AU - Ramos, Eliana Marisa
AU - Osiecki, Lisa
AU - Chen, Jason A.
AU - McGrath, Lauren M.
AU - Illmann, Cornelia
AU - Sandor, Paul
AU - Barr, Cathy L.
AU - Grados, Marco
AU - Singer, Harvey S.
AU - Nöthen, Markus M.
AU - Hebebrand, Johannes
AU - King, Robert A.
AU - Dion, Yves
AU - Rouleau, Guy
AU - Budman, Cathy L.
AU - Depienne, Christel
AU - Worbe, Yulia
AU - Hartmann, Andreas
AU - Müller-Vahl, Kirsten R.
AU - Stuhrmann, Manfred
AU - Aschauer, Harald
AU - Stamenkovic, Mara
AU - Schloegelhofer, Monika
AU - Konstantinidis, Anastasios
AU - Lyon, Gholson J.
AU - McMahon, William M.
AU - Barta, Csaba
AU - Tarnok, Zsanett
AU - Nagy, Peter
AU - Batterson, James R.
AU - Rizzo, Renata
AU - Cath, Danielle C.
AU - Wolanczyk, Tomasz
AU - Berlin, Cheston
AU - Malaty, Irene A.
AU - Okun, Michael S.
AU - Woods, Douglas W.
AU - Rees, Elliott
AU - Pato, Carlos N.
AU - Pato, Michele T.
AU - Knowles, James A.
AU - Posthuma, Danielle
AU - Pauls, David L.
N1 - Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/6/21
Y1 - 2017/6/21
N2 - 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. Tourette syndrome is highly genetic, but identifying definitive disease susceptibility genes has been challenging. Huang et al. report two genome-wide, significant, recurrent, rare copy-number variants (NRXN1 deletions and CNTN6 duplications), each conferring a substantial increase in TS risk.
AB - 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. Tourette syndrome is highly genetic, but identifying definitive disease susceptibility genes has been challenging. Huang et al. report two genome-wide, significant, recurrent, rare copy-number variants (NRXN1 deletions and CNTN6 duplications), each conferring a substantial increase in TS risk.
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U2 - 10.1016/j.neuron.2017.06.010
DO - 10.1016/j.neuron.2017.06.010
M3 - Article
C2 - 28641109
AN - SCOPUS:85027263762
SN - 0896-6273
VL - 94
SP - 1101-1111.e7
JO - Neuron
JF - Neuron
IS - 6
ER -