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Common variants on 8p12 and 1q24.2 confer risk of schizophrenia

Abstract

Schizophrenia is a severe mental disorder affecting 1% of the world population, with heritability of up to 80%. To identify new common genetic risk factors, we performed a genome-wide association study (GWAS) in the Han Chinese population. The discovery sample set consisted of 3,750 individuals with schizophrenia and 6,468 healthy controls (1,578 cases and 1,592 controls from northern Han Chinese, 1,238 cases and 2,856 controls from central Han Chinese, and 934 cases and 2,020 controls from the southern Han Chinese). We further analyzed the strongest association signals in an additional independent cohort of 4,383 cases and 4,539 controls from the Han Chinese population. Meta-analysis identified common SNPs that associated with schizophrenia with genome-wide significance on 8p12 (rs16887244, P = 1.27 × 10−10) and 1q24.2 (rs10489202, P = 9.50 × 10−9). Our findings provide new insights into the pathogenesis of schizophrenia.

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Figure 1: Regional plots of the two loci associated with schizophrenia.

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Acknowledgements

We are deeply grateful to all the participants as well as to the doctors working on this project. The authors also thank the editors and anonymous reviewers for their valuable comments on the manuscript. This work was supported by grants from the 973 Program (2010CB529600, 2009AA022701, 2006AA02A407), the Natural Science Foundation of China (81130022, 81121001, 31000553), the Foundation for the Author of National Excellent Doctoral Dissertation of China (201026), the Program for New Century Excellent Talents in University (NCET-09-0550), the Shanghai Municipal Health Bureau program (2008095), the Shanghai Changning Health Bureau program (2008406002), the Shanghai Municipal Commission of Science and Technology Program (09DJ1400601), the National Key Technology R&D Program (2006BAI05A09) and the Shanghai Leading Academic Discipline Project (B205).

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Authors

Contributions

Y.S. and L.H. conceived of and designed the study. Y.S. supervised all the experiments and data analysis. Y.S. and Z.L. conducted data analyses and drafted the manuscript. Y.S., Z.L., F.Z., D.S.C., S.S., D.R. and L.H. revised the manuscript. Y.S., G.F., Q.X., J.C., Y.X., D.L., P.W., P.Y., B. Liu, W.S., G.Z. and W.J. recruited samples. T. Wang, J.J., T.L., J.S., J.C., Q.W., W.L., L.Z., H.Z., B. Li, C.W., S.Q. and G.H. performed or contributed to the experiments. S.S., S.C., T.W., E.S., S.T., A.P., M.M.N., M.R., R.A.O., D.A.C., D.R., D.S.C., H.S. and K.S. provided the SGENE-plus data. All authors critically reviewed and approved the manuscript.

Corresponding authors

Correspondence to Yongyong Shi or Lin He.

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The authors declare no competing financial interests.

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Supplementary Figures 1–4, Supplementary Tables 1–12 and Supplementary Note (PDF 463 kb)

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Shi, Y., Li, Z., Xu, Q. et al. Common variants on 8p12 and 1q24.2 confer risk of schizophrenia. Nat Genet 43, 1224–1227 (2011). https://doi.org/10.1038/ng.980

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