Genome-wide association study identifies a susceptibility locus for schizophrenia in Han Chinese at 11p11.2

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Abstract

To identify susceptibility loci for schizophrenia, we performed a two-stage genome-wide association study (GWAS) of schizophrenia in the Han Chinese population (GWAS: 746 individuals with schizophrenia and 1,599 healthy controls; validation: 4,027 individuals with schizophrenia and 5,603 healthy controls). We identified two susceptibility loci for schizophrenia at 6p21-p22.1 (rs1233710 in an intron of ZKSCAN4, Pcombined = 4.76 × 10−11, odds ratio (OR) = 0.79; rs1635 in an exon of NKAPL, Pcombined = 6.91 × 10−12, OR = 0.78; rs2142731 in an intron of PGBD1, Pcombined = 5.14 × 10−10, OR = 0.79) and 11p11.2 (rs11038167 near the 5′ UTR of TSPAN18, Pcombined = 1.09 × 10−11, OR = 1.29; rs11038172, Pcombined = 7.21 × 10−10, OR = 1.25; rs835784, Pcombined = 2.73 × 10−11, OR = 1.27). These results add to previous evidence of susceptibility loci for schizophrenia at 6p21-p22.1 in the Han Chinese population. We found that NKAPL and ZKSCAN4 were expressed in postnatal day 0 (P0) mouse brain. These findings may lead to new insights into the pathogenesis of schizophrenia.

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Figure 1: Regional plots of the two loci associated with schizophrenia at 6p21-p22.1 and 11p11.2.

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Acknowledgements

We thank J. Liu from the Human Genetics, Genome Institute of Singapore for his suggestions for revision of the manuscript. We acknowledge with appreciation all the individuals with schizophrenia and healthy control subjects whose contributions made this work possible. This work was supported by research grants from the National High-Tech Research and Development Program of China (2009AA022702), the National Natural Science Foundation of China (30530290, 30870896, 81071087 and 81071088), the National Basic Research Program of China (2007CB512301, 2011CB707805) and the International Science & Technology Cooperation Program of China (2010DFB30820).

Author information

D.Z., W.H., X.-J.Z., G.-P.Z. and T.L. designed the study. D.Z. and X.-J.Z. revised the manuscript. D.Z. and W.-H.Y. obtained financial support. W.-H.Y., L.-D.S. and L.-F.W. prepared the manuscript. H.-F.W., W.-H.Y. and L.-D.S. supervised the experiments and data analysis. H.-X.Z., W.-Q.L., Y.-L.Z., C.-C.M., B.D., Y.-Q.R., Y.-F.Y., X.-F.H., Y.W., W.D., L.-W.T., Y.-L.T., Q.C., G.-M.X., G.-G.Y., H.Y., Y.-Y.R., T.-L.L., X.H., X.-H.M., Y.W., L.-W.C., C.J., H.-Y.Z., J.Y., W.-F.M., X.-Y.Y., W.-B.M., Q.L., L.K., W.S., C.-Y.P., M.S., F.-D.Y., C.-Y.W., J.-L.Y., K.-Q.L., X.M., L.-J.L., X.Y. and L.-X.L. conducted sample selection and data management, undertook recruitment, collected phenotype data, undertook related data handling and calculation, managed recruitment and obtained biological samples. W.-H.Y., L.-F.W., X.B.Z. and Q.-Z.L. undertook data processing, statistical analysis and bioinformatics investigations. F.-L.T., Z.-H.L., Y.Z. and X.H. performed in situ hybridization and RNAi experiments. All authors critically reviewed the manuscript and approved the final version.

Correspondence to Wei Huang or Dai Zhang.

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The authors declare no competing financial interests.

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Supplementary Tables 1–6, Supplementary Figures 1–6 and Supplementary Note (PDF 2238 kb)

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