Table 2.
Candidate regulatory variants
| Chr:pos | Ref | Alt | rsID | Transcription factor | EMSA | OR | GERP |
|---|---|---|---|---|---|---|---|
| CTTNBP2 | |||||||
| chr7:117356081 | T | G | None | CTCF (GB, NB), RAD21 (NB, ESC) | c | Privatee | b |
| chr7:117390966 | T | Del | None | CTCF (NB, CB), RAD21 (ESC) | d | Privatee | b |
| chr7:117417559 | A | G | rs75322384 | b | c | 2.2 | Conserved |
| chr7:117421141 | C | A | None | b | d | Privatee | Conserved |
| chr7:117431202a | C | A | None | b | b | Privatee | Conserved |
| chr7:117431704a | C | T | None | RAD21 (ESC) | d | Privatee | Conserved |
| chr7:117431879a | G | A | None | b | c | Privatee | b |
| chr7:117450810 | C | T | rs34868515 | SP1, YY1, EP300, JUND, TCF12, HDAC2, NANOG, BCL11A, TEAD4 (all ESC) | b | Private | b |
| chr7:117456904 | C | T | rs12706157 | b | c | 1.06 | b |
| chr7:117457141 | G | C | rs13242822 | b | b | 1.04 | b |
| chr7:117468056 | C | T | rs2067080 | EP300 (NB), FOXP2 (NB), JUND (ESC) | b | 1.1 | Conserved |
| chr7:117468334 | T | C | rs2111209 | EP300 (NB), FOXP2 (NB), JUND (ESC) | b | 1.04 | b |
| REEP3 | |||||||
| chr10:65307923 | A | G | rs78109635 | GATA2 (NB) | c | 1.01 | Diverged |
| chr10:65332906 | T | C | rs76646063 | GATA3, GATA2, EP300 (all NB) | c | 3.7 | Conserved |
| chr10:65387644 | C | G | rs56311840 | b | b | Privatee | b |
| chr10:65387722 | C | Del | None | b | d | Privatee | b |
| chr10:65388750 | G | A | None | SIN3A (NB), POLR2A (NB), REST (NB), USF1 (ESC), EP300 (NB) | b | Privatee | b |
We identified twelve candidate regulatory SNPs in CTTNBP2, including: seven intronic SNPs with DHS signals in neural stem cells (SK-N-MC) or neuroblasts (SK-N-SH, BE2-C, SH-SY5Y, SK-N-SH-RA), four of which also overlap TF-binding sites in the brain-derived cell lines; two intronic SNPs near the top DHS variants and potentially altering the same regulatory elements; and three coding SNPs that lie within or near regulatory marks (Supplementary Fig. 7b). We also identified five candidate regulatory SNPs in or near REEP3, including: one intronic SNP (chr10:65307923) in a DHS and GATA2 TFBS active in neuroblasts; one intronic SNP (chr10:65332906) that alters a DHS active in neural stem cells and GATA2, GATA3, and EP300 binding sites active in neuroblasts; three noncoding SNPs (chr10:65387644, chr10:65387722, and chr10:65388750) that cluster ~3 kb upstream in a DHS active in multiple brain-related cells, including neuroblasts, and are seen only in OCD patients in our pooled sequencing (Supplementary Fig. 7c) Del, deletion.
aCoding; EMSA, electrophoretic mobility shift assay
bNo change
cStrong TF-DNA binding change
dWeak change; GB, glioblast; NB, neuroblast; ESC, embryonic stem cell; CB, cerebellum; “Transcription factor” column shows the TF bindings to the regions and brain/developmental cell types where the signals are found. OR (odds ratio) column reports data in the combined set, unless noted with
eIndicating data from sequencing