Table 1.
Genetic Loci With conjFDR < 0.05 Shared Between SCZ and Brain Structure Volumes
| Locus | Marker | Nearest Gene (Annotation) | Chr | A1/A2 | Z-Score SCZ | Z-Score Brain Volume | ConjFDR | P-Value SCZ16 | P-Value Brain Volume5 | Variance Explained SCZ (%) | Variance Explained Brain Volume (%) | Other Genes in Genomic Region Defined by LD | ENIGMA2 and CHARGE Combined GWAS20,22 (n ≥ 26577) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SCZ (n = 82315) and hippocampal volume (n = 11621) | |||||||||||||
| 1 | rs4664442a | SLC4A10 (intron) | 2q24.2 | G/A | −4.32 | −4.82 | 4.16e-03 | 1.56e-05 | 1.41e-06 | 0.17 | 0.20 | DPP4 | 2.53E-10 |
| 2 | rs1653290a | SPATS2L (intergenic) | 2q33.1 | A/T | NAb | NA | 3.83e-02 | 5.44e-07 | 1.82e-04 | 0.21 | 0.12 | — | 1.46E-01 |
| SCZ (n = 82315) and ICV (n = 9826) | |||||||||||||
| 3 | rs4687658a | ITIH4 (intron) | 3p21.1 | C/G | NAb | NA | 2.31e-02 | 1.49e-05 | 1.09e-04 | 0.18 | 0.15 | TMEM110, MUSTN1, SFMBT1 | 3.50E-04 |
| 4 | rs10457180 | FOXO3 (intron) | 6q21 | G/A | 4.20 | −4.14 | 7.11e-03 | 2.72e-05 | 3.43e-05 | 0.16 | 0.18 | — | 4.12E-11 |
| SCZ (n = 82315) and volume of putamen (n = 11598) | |||||||||||||
| 5 | rs11233632c | DLG2 (intron) | 11q14.1 | C/T | 3.98 | 4.14 | 1.30e-02 | 6.89e-05 | 3.41e-05 | 0.13 | 0.15 | — | — |
| 6 | rs4632195c | DCC (intron) | 18q21.2 | C/T | −3.66 | −4.10 | 4.26e-02 | 2.49e-04 | 4.11e-05 | 0.12 | 0.15 | — | — |
Independent complex or single gene loci (r2 < .1) with single nucleotide polymorphisms with a conjFDR < 0.05 shared between SCZ and volumes of hippocampus, putamen, and ICV. The most significant SNPs in each LD block are listed. Chromosomal position, closest gene, z-scores and P-values in the phenotypes, the percentage variance in SCZ and brain volumes explained by each variant, and other genes in genomic region defined by LD > 0.6 are also listed. The effect sizes are given with reference to allele 1 (A1). All data were first corrected for genomic inflation, and the MHC-region was excluded from the FDR computation. Chr, chromosome; A1, allele number 1; A2, allele number 2; NA, not available z-score signs due to A–T and C–G polymorphisms; conjFDR, conjunctional false discovery rate; GWAS, genome-wide association study; ICV, intracranial volume; LD, linkage disequilibrium; MAF, minor allele frequency; SCZ, schizophrenia.
aLoci identified by the primary SCZ GWAS.16
bSNPs in strong LD with rs1653290 show the same effect directions in hippocampal volume and SCZ, and SNPs in strong LD with rs4687658 showed the same effect directions in ICV and SCZ (supplementary table 3).
cLoci identified by the primary brain structure volume GWAS.5