Recently, two genome-wide association studies (GWASs) of schizophrenia (SCZ) in Han Chinese identified several susceptibility loci. Replication efforts aiming to validate the GWAS findings were made and focused on the top hits. We conducted a more extensive follow-up study in an independent sample of 1471 cases and 1528 matched controls to verify 26 genetic variants by including nine top single-nucleotide polymorphisms (SNPs) that reached genome-wide significance and 17 promising SNPs nominated in the initial discovery phase. rs8073471 in an intron of tubulin-folding cofactor D (TBCD) obtained nominal significance ( P <0.01) in single SNP analysis. Logistic regression identified significant interaction between rs3744165 (5’-untranslated region variant of exon 2 of zinc finger protein 750 (ZNF750), and in an intron of TBCD) and rs8073471 (Deviance test P -value=2.77 × 10 −34 ). Both SNPs are located at 17q25, an interesting region that has been implicated in SCZ. By using the Genotype-Tissue Expression (GTEx) data set, we implemented an expression quantitative trait loci epistasis analysis to explore the association between the genotype combinations of the two SNPs and gene expression levels in 13 areas of human central nervous system. We observed that rs3744165 × rs8073471 interaction modulated the expression profile of TEAD3 ( P =1.87 × 10 −8 ), SH3TC2 ( P =2.00 × 10 −8 ), KCNK9 ( P =5.20 × 10 −7 ) and PPDPF ( P =1.13 × 10 −6 ) in postmortem cortex tissue; EFNA1 ( P =7.26 × 10 −9 ), RNU4ATAC ( P =2.32 × 10 −8 ) and NUPL2 ( P =6.79 × 10 −8 ) in cerebellum tissue. To the best of our knowledge, our study is the first one that links TBCD and ZNF750 mutations to SCZ susceptibility and to the transcript levels in human brain tissues. Further efforts are needed to understand the role of those variants in the pathogenesis of SCZ.

BACKGROUND AND PURPOSE: In patients with carotid stenosis or occlusion, cerebral blood could be supplied through collateral pathways to improve regional blood flow and protect against ischemic events. The contribution of collaterals from the ICA can be assessed by depiction of vascular perfusion territories with ASL. However, so far there is no method available to evaluate the collateral perfusion territory from the ECA in MR imaging. In this study, we present a new labeling scheme based on VE-ASL to quantitatively assess the perfusion territory of the ECA. MATERIALS AND METHODS: A new labeling approach with a Hadamard encoding scheme was developed to label major arteries, especially the ECA. Twelve healthy subjects with normal cerebrovascular anatomy were examined to demonstrate their perfusion territories. Eight patients with carotid artery stenosis or occlusion were assessed before and after surgery to show changes of their collateral blood supply. RESULTS: The proposed method enables assessment of the perfusion territories of the ECA. Good agreement was found between the vascular territories and normal cerebrovascular anatomy in healthy subjects. For the patients with carotid stenosis or occlusion, our noninvasive results provided information on collateral flow comparable with that from DSA. Their collateral flows from the ECA, moreover, could be quantitatively estimated pre- and postoperatively. CONCLUSIONS: The modified approach has been validated by the consistency of collateral perfusion territories with cerebrovascular anatomy, and quantitative assessment of collaterals proved useful for assisting in evaluating therapeutic interventions.

BACKGROUND AND PURPOSE: Current knowledge of the collateral circulation remains sparse, and a noninvasive method to better characterize the role of collaterals is desirable. The aim of our study was to investigate the presence and distal flow of collaterals by using a new MR perfusion territory imaging, vessel-encoded arterial spin-labeling (VE-ASL). MATERIALS AND METHODS: Fifty-six patients with internal carotid artery (ICA) or middle cerebral artery (MCA) stenosis were identified by sonography, VE-ASL was performed to assess the presence and function of collateral flow. The perfusion information was combined with VE maps into high signal-intensity-to-noise-ratio 3-colored maps of the left carotid, right carotid, and posterior circulation territories. The presence of the anterior and posterior collateral flow was demonstrated by the color of the standard anterior cerebral artery/MCA flow territory. The distal function of collateral flow was categorized as adequate (cerebral blood flow [CBF] >= 10 mL/min/100 g) or deficient (CBF <10 mL/min/100 g). The results were compared with those of MR angiography (MRA) and intra-arterial digital subtraction angiography (DSA) in cross table, and K coefficients were calculated to determine the agreement among different methods. RESULTS: The K coefficients of the presence of anterior and posterior collaterals by using VE-ASL and I were 0.785 and 0.700, respectively. The kappa Coefficient of the function of collaterals by using VE-ASL and DSA was 0.726. Apart from collaterals through the circle of Willis, VE-ASL showed collateral flow via leptomeningeal anastomoses. CONCLUSIONS: In patients with ICA or MCA stenosis, VE-ASL could show the presence, the origin, and distal function of collateral flow noninvasively.