Table 1.
Integrative Analysis (Sherlock) of Schizophrenia GWAS and Brain eQTL Reveals That ZNF323 Had the Most Significant Association With Schizophrenia
| Gene symbol | LBFa | P-valueb | Supporting SNPc (cis or trans) | PeQTL d | P GWAS e | FDRf |
|---|---|---|---|---|---|---|
| ZNF323 | 7.09 | 2.22×10–6 | rs2859365 (cis) | 5.90×10–8 | 2.07×10–7 | 3.69×10–3 |
| NAPSA | 7.04 | 2.22×10–6 | rs10226475 (trans) | 6.74×10–6 | 2.02×10−10 | 3.69×10–3 |
| LOC378135 | 6.76 | 2.22×10–6 | rs134169 (trans) | 6.17×10–6 | 2.50×10–5 | 3.69×10–3 |
| EPB41L2 | 6.66 | 2.22×10–6 | rs7752195 (trans) | 1.17×10–6 | 1.82×10–5 | 3.69×10–3 |
| GLT8D1 | 5.83 | 4.43×10–6 | rs2240920 (cis) | 5.22×10–16 | 7.30×10–6 | 7.35×10–3 |
| RCN1 | 5.83 | 4.43×10–6 | rs3800917 (trans) | 6.56×10–7 | 6.27×10−10 | 7.35×10–3 |
| ALMS1 | 5.56 | 1.11×10–5 | rs6753344 (cis) | 1.37×10–9 | 5.00×10–5 | 1.84×10–2 |
| EIF4A2 | 5.39 | 1.11×10–5 | rs17002034 (trans) | 4.00×10–7 | 1.40×10–6 | 1.84×10–2 |
| MPV17L2 | 5.30 | 1.11×10–5 | rs7752195 (trans) | 1.54×10–6 | 1.82×10–5 | 1.84×10–2 |
| LSAMP | 5.13 | 1.11×10–5 | rs4976976 (trans) | 4.53×10–7 | 6.23×10–6 | 1.84×10–2 |
| CSNK2B | 5.11 | 1.11×10–5 | rs707939 (cis) | 5.35×10–6 | 8.23×10–5 | 1.84×10–2 |
| PLCD4 | 5.09 | 1.55×10–5 | rs2160567 (trans) | 7.40×10–7 | 8.29×10–6 | 2.57×10–2 |
aLBF (Log Bayes Factors for each gene) evaluates whether the combined evidence from GWAS and expression studies support a gene being associated with schizophrenia. For example, a LBF of 4.6 means that the alternative hypothesis (associated with Schizophrenia) is 100 times (exp[4.6] = 100) more likely than the null hypothesis (no association). High Bayes factors tend to correlate with low P-values. Several eSNPs may be associated with the expression of a gene. For each of these eSNP, if it is also associated with schizophrenia in GWAS, a positive score would be given; otherwise, a negative score. Association only in GWAS (ie, non-eSNPs) does not alter the score. The total score of a gene increases with the number of SNPs with combined evidence (SNPs that are associated with schizophrenia and expression). For each gene, Sherlock computes individual LBFs for each SNP pair in the alignment, and the sum of these constitutes the final LBF score for the gene.
b P-value from Sherlock integrative analysis.
cSNP with the highest LBF score.
d P-value for eQTL SNP from the gene expression study.18
e P-value for eQTL SNP from the GWAS of schizophrenia.11
fFDR was calculated at P = 10–5 threshold. It should be noted that some genes with different LBF scores may have the same P-values. This is because that Sherlock computes P-values by finite permutations. If the number of permutation is not extremely high, it is possible that two different values of LBF correspond to the same P-values (their rankings are the same). Genes with LBF > 5.0 and P-value < 10–4 are listed.