Rare Copy Number Variants in NRXN1 and CNTN6 Increase Risk for Tourette Syndrome.
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 Mb), singleton events (OR = 2.28, 95% CI [1.39-3.79], p = 1.2 × 10) and known, pathogenic CNVs (OR = 3.03 [1.85-5.07], p = 1.5 × 10). 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.
|Year of Publication||
2017 Jun 21
|PubMed Central ID||
K23 MH085057 / MH / NIMH NIH HHS / United States
U54 HD087101 / HD / NICHD NIH HHS / United States
U01 NS040024 / NS / NINDS NIH HHS / United States
R01 MH096767 / MH / NIMH NIH HHS / United States
P30 NS062691 / NS / NINDS NIH HHS / United States
R01 NS016648 / NS / NINDS NIH HHS / United States
K02 NS085048 / NS / NINDS NIH HHS / United States
R01 NS040024 / NS / NINDS NIH HHS / United States
U01 MH109514 / MH / NIMH NIH HHS / United States