The second top SNP in the primary analysis, rs6539267, is located on chromosome 12q23 within an intron of POLR3B. This gene encodes the second largest subunit of RNA polymerase III, which transcribes eukaryotic non-coding RNAs including tRNAs, small rRNAs and microRNAs.38 Recessive mutations in POLR3B cause hypomyelinating leukodystrophy with a severe neurological phenotype (developmental delay, spasticity, dysarthria and ataxia), though no reported tics.39-40 Both the secondary meta-analysis and imputed data provide additional support for this locus, and expand the region of LD to ~300kb, including adjacent genes CKAP4, TCP11L2 and RFX4 (Table S5, Figure S10).
