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. Author manuscript; available in PMC: 2019 Jul 5.
Published in final edited form as: Mol Psychiatry. 2019 Jan 4;26(2):508–523. doi: 10.1038/s41380-018-0314-z

Figure 2. Human CPG2 variants identified by deep-sequencing.

Figure 2.

Brain tissue gDNA was extracted from all patient and control subjects, and deep-sequenced in the CPG2 locus to identify genetic variants. Common BD associated variants identified from GWASs26, 33, 61, 62 were statistically tested for correlation with CPG2 protein expression levels. A) The genomic position (GRCh37 assembly) of five SNPs identified as BD associated by GWAS mapped onto the CPG2 region of SYNE1 (dark blue vertical bars represent exons) shown in the context of previously published ChIP-sequencing data from human neurons identifying active promoter (green) and enhancer (purple) regions43. The five SNPs are rs4523096 (green*), rs7747960 (red*), rs9371601 (blue*), rs214972 (yellow*) and rs215006 (grey*). B) The allele frequencies of the five BD associated SNPs were quantified for high and low CPG2 expression subjects. C) Six LD proxies (rs9478332, rs12055686, rs4343926, rs4318888, rs7771568, and rs6908747) for the five BD SNPs map to the CPG2 TSS flanking region (color-matched to origin SNPs). D) The LD allele frequencies of the six SNP proxies were quantified for high and low CPG2 expression subjects. Four alleles (rs4523096[T], rs7747960[T], rs9478332[T] and rs4343926[C]) were trending towards higher allele frequency in low expressing subjects. E) The frequency of having at least one of the four non-reference alleles was compared between high and low CPG2 expression subjects, and F) between BD patients with low CPG2 and control subjects (Mann-Whitney binary tests). Note: rs4523096[T] and rs4343926[C] have high allele frequencies (>0.4) and were quantified for homozygous subjects in E, F and G. G) CPG2 protein expression levels (from figure 1) are displayed on a continuum from low (red) to high (blue) expression, where each colored bar represents one subject and each of the four identified variants enriched in the low CPG2 population shown as dark grey bars. The threshold between high and low CPG2 expression (dashed red line) was defined at the mean CPG2 protein expression level of the BD group as displayed in Figure 1C.