Fig. 5.

Disruption of CTCF binding by risk single-nucleotide polymorphisms (SNPs; rs12912934 and rs16937). a SNP rs12912934 is located in CTCF binding motif and disrupts occupied CTCF binding site. The matched position weight matrix (PWM) and the location of rs12912934 (red dotted line) are shown. DNase-Seq and chromatin immunoprecipitation and sequencing (ChIP-Seq) experiments showed that rs12912934 is located in an actively transcribed region, with strong DNase-Seq and ChIP-Seq signals. b–d Reporter gene assays revealed that the allelic differences at the rs12912934 affected the luciferase activity significantly in SK-N-SH (c) and SH-SY5Y cells (d). e SNP rs16937 is located in CTCF binding motif, a region with strong ChIP-Seq signals in brain tissues or neuronal cell lines. f–h Reporter gene assays showed that the allelic differences at the rs16937 influenced the luciferase activity significantly in HEK293 (f) and SH-SY5Y cells (h). Data represent mean ± SD; n = 8 for each group in b, f (HEK293 cells) and c, g (SK-N-SH cells); n = 16 for each group in d, h (SH-SY5Y cells). NS, not significant, *P < 0.05, ***P < 0.001, two-tailed Student’s t-test. Source data are provided as a Source Data file