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Loci with genome-wide associations with schizophrenia in the Han Chinese population

  • Zhiqiang Li (a1), Yuqian Xiang (a2), Jianhua Chen (a3), Qiaoli Li (a4), Jiawei Shen (a3), Yun Liu (a5), Wenjin Li (a3), Qinghe Xing (a5), Qingzhong Wang (a3), Lei Wang (a5), Guoyin Feng (a6), Lin He (a1), Xinzhi Zhao (a2) and Yongyong Shi (a7)...

Abstract

Background

A large schizophrenia genome-wide association study (GWAS) and a subsequent extensive replication study of individuals of European ancestry identified eight new loci with genome-wide significance and suggested that the MIR137-mediated pathway plays a role in the predisposition for schizophrenia.

Aims

To validate the above findings in a Han Chinese population.

Method

We analysed the single nucleotide polymorphisms (SNPs) in the newly identified schizophrenia candidate loci and predicted MIR137 target genes based on our published Han Chinese populations (BIOX) GWAS data. We then analysed 18 SNPs from the candidate regions in an independent cohort that consisted of 3585 patients with schizophrenia and 5496 controls of Han Chinese ancestry.

Results

We replicated the associations of five markers (P<0.05), including three that were located in the predicted MIR137 target genes. Two loci (ITIH3/4: rs2239547, P =1.17×10–10 and CALN1: rs2944829, P=9.97×10–9) exhibited genome-wide significance in the Han Chinese population.

Conclusions

The ITIH3/4 locus has been reported to be of genome-wide significance in the European population. The successful replication of this finding in a different ethnic group provides stronger evidence for the association between schizophrenia and ITIH3/4. We detected the first genome-wide significant association of schizophrenia with CALN1, which is a predicted target of MIR137, and thus provide new evidence for the associations between MIR137 targets and schizophrenia.

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Copyright

Corresponding author

Yongyong Shi, Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, People's Republic of China. Email: shiyongyong@gmail.com; Xinzhi Zhao, Children's Hospital, Fudan University, 138 Yixueyuan Road, Shanghai 200032, People's Republic of China. Email: xzzhau@fudan.edu.cn

Footnotes

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Declaration of interest

None.

Footnotes

References

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1 van Os, J, Kapur, S. Schizophrenia. Lancet 2009; 374: 635–45.
2 Lichtenstein, P, Yip, BH, Bjork, C, Pawitan, Y, Cannon, TD, Sullivan, PF, et al. Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study. Lancet 2009; 373: 234–9.
3 Sullivan, PF, Kendler, KS, Neale, MC. Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. Arch Gen Psychiatry 2003; 60: 1187–92.
4 Lencz, T, Morgan, TV, Athanasiou, M, Dain, B, Reed, CR, Kane, JM, et al. Converging evidence for a pseudoautosomal cytokine receptor gene locus in schizophrenia. Mol Psychiatry 2007; 12: 572–80.
5 Shifman, S, Johannesson, M, Bronstein, M, Chen, SX, Collier, DA, Craddock, NJ, et al. Genome-wide association identifies a common variant in the reelin gene that increases the risk of schizophrenia only in women. PLoS Genet 2008; 4: e28.
6 Kirov, G, Zaharieva, I, Georgieva, L, Moskvina, V, Nikolov, I, Cichon, S, et al. A genome-wide association study in 574 schizophrenia trios using DNA pooling. Mol Psychiatry 2008; 14: 796803.
7 Sullivan, PF, Lin, D, Tzeng, JY, van den Oord, E, Perkins, D, Stroup, TS, et al. Genomewide association for schizophrenia in the CATIE study: results of stage 1. Mol Psychiatry 2008; 13: 570–84.
8 Walsh, T, McClellan, JM, McCarthy, SE, Addington, AM, Pierce, SB, Cooper, GM, et al. Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Sci Signalling 2008; 320: 539.
9 Stefansson, H, Ophoff, RA, Steinberg, S, Andreassen, OA, Cichon, S, Rujescu, D, et al. Common variants conferring risk of schizophrenia. Nature 2009; 460: 744–7.
10 Need, AC, Ge, D, Weale, ME, Maia, J, Feng, S, Heinzen, EL, et al. A genome-wide investigation of SNPs and CNVs in schizophrenia. PLoS Genet 2009; 5: e1000373.
11 O'Donovan, MC, Craddock, N, Norton, N, Williams, H, Peirce, T, Moskvina, V, et al. Identification of loci associated with schizophrenia by genome-wide association and follow-up. Nat Genet 2008; 40: 1053–5.
12 Purcell, SM, Wray, NR, Stone, JL, Visscher, PM, O'Donovan, MC, Sullivan, PF, et al. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 2009; 460: 748–52.
13 Schizophrenia Psychiatric Genome-Wide Association Study C. Genome-wide association study identifies five new schizophrenia loci. Nat Genet 2011; 43: 969–76.
14 Yue, WH, Wang, HF, Sun, LD, Tang, FL, Liu, ZH, Zhang, HX, et al. Genome-wide association study identifies a susceptibility locus for schizophrenia in Han Chinese at 11p11.2. Nat Genet 2011; 43: 1228–31.
15 Shi, Y, Li, Z, Xu, Q, Wang, T, Li, T, Shen, J, et al. Common variants on 8p12 and 1q24.2 confer risk of schizophrenia. Nat Genet 2011; 43: 1224–7.
16 Bergen, SE, O'Dushlaine, CT, Ripke, S, Lee, PH, Ruderfer, DM, Akterin, S, et al. Genome-wide association study in a Swedish population yields support for greater CNV and MHC involvement in schizophrenia compared with bipolar disorder. Mol Psychiatry 2012; 17: 880–6.
17 Strange, A, Riley, BP, Spencer, CCA, Morris, DW, Pirinen, M, O'Dushlaine, CT, et al. Genome-wide association study implicates HLA-C* 01: 02 as a risk factor at the major histocompatibility complex locus in schizophrenia. Biol Psychiatry 2012; 72: 620–8.
18 Levinson, DF, Shi, J, Wang, K, Oh, S, Riley, B, Pulver, AE, et al. Genome-wide association study of multiplex schizophrenia pedigrees. Am J Psychiatry 2012; 169: 963–73.
19 Betcheva, ET, Yosifova, AG, Mushiroda, T, Kubo, M, Takahashi, A, Karachanak, SK, et al. Whole-genome-wide association study in the Bulgarian population reveals HHAT as schizophrenia susceptibility gene. Psychiatr Genet 2013; 23: 11–9.
20 Shi, J, Levinson, DF, Duan, J, Sanders, AR, Zheng, Y, Pe'er, I, et al. Common variants on chromosome 6p22.1 are associated with schizophrenia. Nature 2009; 460: 753–7.
21 Purcell, SM, Wray, NR, Stone, JL, Visscher, PM, O'Donovan, MC, Sullivan, PF, et al. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 2009; 460: 748–52.
22 Kim, AH, Parker, EK, Williamson, V, McMichael, GO, Fanous, AH, Vladimirov, VI. Experimental validation of candidate schizophrenia gene ZNF804A as target for hsa-miR-137. Schizophria Res 2012; 141: 60–4.
23 Kwon, E, Wang, W, Tsai, LH. Validation of schizophrenia-associated genes CSMD1, C10orf26, CACNA1C and TCF4 as miR-137 targets. Mol Psychiatry 2013; 18: 11–2.
24 Hamshere, ML, Walters, JT, Smith, R, Richards, AL, Green, E, Grozeva, D, et al. Genome-wide significant associations in schizophrenia to ITIH3/4, CACNA1C and SDCCAG8, and extensive replication of associations reported by the Schizophrenia PGC. Mol Psychiatry 2013: 18: 708–12.
25 Li, T, Li, Z, Chen, P, Zhao, Q, Wang, T, Huang, K, et al. Common variants in major histocompatibility complex region and TCF4 gene are significantly associated with schizophrenia in Han Chinese. Biol Psychiatry 2010; 68: 671–3.
26 Gelernter, J, Kranzler, HR, Sherva, R, Almasy, L, Koesterer, R, Smith, AH, et al. Genome-wide association study of alcohol dependence: significant findings in African- and European-Americans including novel risk loci. Mol Psychiatry 2014; 19: 41–9.
27 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (4th edn) (DSM-IV). APA, 1994.
28 Barrett, JC, Fry, B, Maller, J, Daly, MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005; 21: 263.
29 Purcell, S, Neale, B, Todd-Brown, K, Thomas, L, Ferreira, MAR, Bender, D, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 2007; 81: 559–75.
30 Stranger, BE, Nica, AC, Forrest, MS, Dimas, A, Bird, CP, Beazley, C, et al. Population genomics of human gene expression. Nat Genet 2007; 39: 1217–24.
31 Kashyap, RS, Nayak, AR, Deshpande, PS, Kabra, D, Purohit, HJ, Taori, GM, et al. Inter-alpha-trypsin inhibitor heavy chain 4 is a novel marker of acute ischemic stroke. Clinica Chimica Acta 2009; 402: 160–3.
32 Tsai, KY, Lee, CC, Chou, YM, Su, CY, Chou, FHC. The incidence and relative risk of stroke in patients with schizophrenia: a five-year follow-up study. Schizophr Res 2012; 138: 41–7.
33 Lin, HC, Hsiao, FH, Pfeiffer, S, Hwang, YT, Lee, HC. An increased risk of stroke among young schizophrenia patients. Schizophr Res 2008; 101: 234–41.
34 Wu, YQ, Lin, X, Liu, CM, Jamrich, M, Shaffer, LG. Identification of a human brain-specific gene, calneuron 1, a new member of the calmodulin superfamily. Mol Genet Metab 2001; 72: 343–50.
35 Ripke, S, O'Dushlaine, C, Chambert, K, Moran, JL, Kahler, AK, Akterin, S, et al. Genome-wide association analysis identifies 13 new risk loci for schizophrenia. Nat Genet 2013; 45: 1150–9.
36 Slavotinek, AM, Rosenfeld, JA, Chao, R, Niyazov, D, Eswara, M, Bader, PI, et al. A de novo deletion of CALN1 in a male with a bilateral diaphragmatic defect does not definitely cause this malformation. Am J Med Genet A 2011; 155: 1196–201.
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Loci with genome-wide associations with schizophrenia in the Han Chinese population

  • Zhiqiang Li (a1), Yuqian Xiang (a2), Jianhua Chen (a3), Qiaoli Li (a4), Jiawei Shen (a3), Yun Liu (a5), Wenjin Li (a3), Qinghe Xing (a5), Qingzhong Wang (a3), Lei Wang (a5), Guoyin Feng (a6), Lin He (a1), Xinzhi Zhao (a2) and Yongyong Shi (a7)...

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Loci with genome-wide associations with schizophrenia in the Han Chinese population

  • Zhiqiang Li (a1), Yuqian Xiang (a2), Jianhua Chen (a3), Qiaoli Li (a4), Jiawei Shen (a3), Yun Liu (a5), Wenjin Li (a3), Qinghe Xing (a5), Qingzhong Wang (a3), Lei Wang (a5), Guoyin Feng (a6), Lin He (a1), Xinzhi Zhao (a2) and Yongyong Shi (a7)...
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