Common variants on 2p16.1, 6p22.1 and 10q24.32 are associated with schizophrenia in Han Chinese population

H. Yu, H. Yan, J. Li, Z. Li, X. Zhang, Y. Ma, L. Mei, C. Liu, L. Cai, Q. Wang, F. Zhang, Nakao Iwata, Masashi Ikeda, L. Wang, T. Lu, M. Li, H. Xu, X. Wu, B. Liu, J. YangK. Li, L. Lv, X. Ma, C. Wang, L. Li, F. Yang, T. Jiang, Y. Shi, T. Li, D. Zhang, W. Yue

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Abstract

Many schizophrenia susceptibility loci have been identified through genome-wide association studies (GWASs) in European populations. However, until recently, schizophrenia GWASs in non-European populations were limited to small sample sizes and have yielded few loci associated with schizophrenia. To identify genetic risk variations for schizophrenia in the Han Chinese population, we performed a two-stage GWAS of schizophrenia comprising 4384 cases and 5770 controls, followed by independent replications of 13 single-nucleotide polymorphisms in an additional 4339 schizophrenia cases and 7043 controls of Han Chinese ancestry. Furthermore, we conducted additional analyses based on the results in the discovery stage. The combined analysis confirmed evidence of genome-wide significant associations in the Han Chinese population for three loci, at 2p16.1 (rs1051061, in an exon of VRK2, P=1.14 × 10-12, odds ratio (OR)=1.17), 6p22.1 (rs115070292 in an intron of GABBR1, P=4.96 × 10-10, OR=0.77) and 10q24.32 (rs10883795 in an intron of AS3MT, P=7.94 × 10-10, OR=0.87; rs10883765 at an intron of ARL3, P=3.06 × 10-9, OR=0.87). The polygenic risk score based on Psychiatric Genomics Consortium schizophrenia GWAS data modestly predicted case-control status in the Chinese population (Nagelkerke R 2: 1.7% ∼5.7%). Our pathway analysis suggested that neurological biological pathways such as GABAergic signaling, dopaminergic signaling, cell adhesion molecules and myelination pathways are involved in schizophrenia. These findings provide new insights into the pathogenesis of schizophrenia in the Han Chinese population. Further studies are needed to establish the biological context and potential clinical utility of these findings.

Original languageEnglish
Pages (from-to)954-960
Number of pages7
JournalMolecular Psychiatry
Volume22
Issue number7
DOIs
Publication statusPublished - 01-07-2017

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Schizophrenia
Genome-Wide Association Study
Population
Odds Ratio
Introns
Cell Adhesion Molecules
Genomics
Sample Size
Single Nucleotide Polymorphism
Psychiatry
Exons
Genome

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Yu, H. ; Yan, H. ; Li, J. ; Li, Z. ; Zhang, X. ; Ma, Y. ; Mei, L. ; Liu, C. ; Cai, L. ; Wang, Q. ; Zhang, F. ; Iwata, Nakao ; Ikeda, Masashi ; Wang, L. ; Lu, T. ; Li, M. ; Xu, H. ; Wu, X. ; Liu, B. ; Yang, J. ; Li, K. ; Lv, L. ; Ma, X. ; Wang, C. ; Li, L. ; Yang, F. ; Jiang, T. ; Shi, Y. ; Li, T. ; Zhang, D. ; Yue, W. / Common variants on 2p16.1, 6p22.1 and 10q24.32 are associated with schizophrenia in Han Chinese population. In: Molecular Psychiatry. 2017 ; Vol. 22, No. 7. pp. 954-960.
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abstract = "Many schizophrenia susceptibility loci have been identified through genome-wide association studies (GWASs) in European populations. However, until recently, schizophrenia GWASs in non-European populations were limited to small sample sizes and have yielded few loci associated with schizophrenia. To identify genetic risk variations for schizophrenia in the Han Chinese population, we performed a two-stage GWAS of schizophrenia comprising 4384 cases and 5770 controls, followed by independent replications of 13 single-nucleotide polymorphisms in an additional 4339 schizophrenia cases and 7043 controls of Han Chinese ancestry. Furthermore, we conducted additional analyses based on the results in the discovery stage. The combined analysis confirmed evidence of genome-wide significant associations in the Han Chinese population for three loci, at 2p16.1 (rs1051061, in an exon of VRK2, P=1.14 × 10-12, odds ratio (OR)=1.17), 6p22.1 (rs115070292 in an intron of GABBR1, P=4.96 × 10-10, OR=0.77) and 10q24.32 (rs10883795 in an intron of AS3MT, P=7.94 × 10-10, OR=0.87; rs10883765 at an intron of ARL3, P=3.06 × 10-9, OR=0.87). The polygenic risk score based on Psychiatric Genomics Consortium schizophrenia GWAS data modestly predicted case-control status in the Chinese population (Nagelkerke R 2: 1.7{\%} ∼5.7{\%}). Our pathway analysis suggested that neurological biological pathways such as GABAergic signaling, dopaminergic signaling, cell adhesion molecules and myelination pathways are involved in schizophrenia. These findings provide new insights into the pathogenesis of schizophrenia in the Han Chinese population. Further studies are needed to establish the biological context and potential clinical utility of these findings.",
author = "H. Yu and H. Yan and J. Li and Z. Li and X. Zhang and Y. Ma and L. Mei and C. Liu and L. Cai and Q. Wang and F. Zhang and Nakao Iwata and Masashi Ikeda and L. Wang and T. Lu and M. Li and H. Xu and X. Wu and B. Liu and J. Yang and K. Li and L. Lv and X. Ma and C. Wang and L. Li and F. Yang and T. Jiang and Y. Shi and T. Li and D. Zhang and W. Yue",
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Yu, H, Yan, H, Li, J, Li, Z, Zhang, X, Ma, Y, Mei, L, Liu, C, Cai, L, Wang, Q, Zhang, F, Iwata, N, Ikeda, M, Wang, L, Lu, T, Li, M, Xu, H, Wu, X, Liu, B, Yang, J, Li, K, Lv, L, Ma, X, Wang, C, Li, L, Yang, F, Jiang, T, Shi, Y, Li, T, Zhang, D & Yue, W 2017, 'Common variants on 2p16.1, 6p22.1 and 10q24.32 are associated with schizophrenia in Han Chinese population', Molecular Psychiatry, vol. 22, no. 7, pp. 954-960. https://doi.org/10.1038/mp.2016.212

Common variants on 2p16.1, 6p22.1 and 10q24.32 are associated with schizophrenia in Han Chinese population. / Yu, H.; Yan, H.; Li, J.; Li, Z.; Zhang, X.; Ma, Y.; Mei, L.; Liu, C.; Cai, L.; Wang, Q.; Zhang, F.; Iwata, Nakao; Ikeda, Masashi; Wang, L.; Lu, T.; Li, M.; Xu, H.; Wu, X.; Liu, B.; Yang, J.; Li, K.; Lv, L.; Ma, X.; Wang, C.; Li, L.; Yang, F.; Jiang, T.; Shi, Y.; Li, T.; Zhang, D.; Yue, W.

In: Molecular Psychiatry, Vol. 22, No. 7, 01.07.2017, p. 954-960.

Research output: Contribution to journalArticle

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T1 - Common variants on 2p16.1, 6p22.1 and 10q24.32 are associated with schizophrenia in Han Chinese population

AU - Yu, H.

AU - Yan, H.

AU - Li, J.

AU - Li, Z.

AU - Zhang, X.

AU - Ma, Y.

AU - Mei, L.

AU - Liu, C.

AU - Cai, L.

AU - Wang, Q.

AU - Zhang, F.

AU - Iwata, Nakao

AU - Ikeda, Masashi

AU - Wang, L.

AU - Lu, T.

AU - Li, M.

AU - Xu, H.

AU - Wu, X.

AU - Liu, B.

AU - Yang, J.

AU - Li, K.

AU - Lv, L.

AU - Ma, X.

AU - Wang, C.

AU - Li, L.

AU - Yang, F.

AU - Jiang, T.

AU - Shi, Y.

AU - Li, T.

AU - Zhang, D.

AU - Yue, W.

PY - 2017/7/1

Y1 - 2017/7/1

N2 - Many schizophrenia susceptibility loci have been identified through genome-wide association studies (GWASs) in European populations. However, until recently, schizophrenia GWASs in non-European populations were limited to small sample sizes and have yielded few loci associated with schizophrenia. To identify genetic risk variations for schizophrenia in the Han Chinese population, we performed a two-stage GWAS of schizophrenia comprising 4384 cases and 5770 controls, followed by independent replications of 13 single-nucleotide polymorphisms in an additional 4339 schizophrenia cases and 7043 controls of Han Chinese ancestry. Furthermore, we conducted additional analyses based on the results in the discovery stage. The combined analysis confirmed evidence of genome-wide significant associations in the Han Chinese population for three loci, at 2p16.1 (rs1051061, in an exon of VRK2, P=1.14 × 10-12, odds ratio (OR)=1.17), 6p22.1 (rs115070292 in an intron of GABBR1, P=4.96 × 10-10, OR=0.77) and 10q24.32 (rs10883795 in an intron of AS3MT, P=7.94 × 10-10, OR=0.87; rs10883765 at an intron of ARL3, P=3.06 × 10-9, OR=0.87). The polygenic risk score based on Psychiatric Genomics Consortium schizophrenia GWAS data modestly predicted case-control status in the Chinese population (Nagelkerke R 2: 1.7% ∼5.7%). Our pathway analysis suggested that neurological biological pathways such as GABAergic signaling, dopaminergic signaling, cell adhesion molecules and myelination pathways are involved in schizophrenia. These findings provide new insights into the pathogenesis of schizophrenia in the Han Chinese population. Further studies are needed to establish the biological context and potential clinical utility of these findings.

AB - Many schizophrenia susceptibility loci have been identified through genome-wide association studies (GWASs) in European populations. However, until recently, schizophrenia GWASs in non-European populations were limited to small sample sizes and have yielded few loci associated with schizophrenia. To identify genetic risk variations for schizophrenia in the Han Chinese population, we performed a two-stage GWAS of schizophrenia comprising 4384 cases and 5770 controls, followed by independent replications of 13 single-nucleotide polymorphisms in an additional 4339 schizophrenia cases and 7043 controls of Han Chinese ancestry. Furthermore, we conducted additional analyses based on the results in the discovery stage. The combined analysis confirmed evidence of genome-wide significant associations in the Han Chinese population for three loci, at 2p16.1 (rs1051061, in an exon of VRK2, P=1.14 × 10-12, odds ratio (OR)=1.17), 6p22.1 (rs115070292 in an intron of GABBR1, P=4.96 × 10-10, OR=0.77) and 10q24.32 (rs10883795 in an intron of AS3MT, P=7.94 × 10-10, OR=0.87; rs10883765 at an intron of ARL3, P=3.06 × 10-9, OR=0.87). The polygenic risk score based on Psychiatric Genomics Consortium schizophrenia GWAS data modestly predicted case-control status in the Chinese population (Nagelkerke R 2: 1.7% ∼5.7%). Our pathway analysis suggested that neurological biological pathways such as GABAergic signaling, dopaminergic signaling, cell adhesion molecules and myelination pathways are involved in schizophrenia. These findings provide new insights into the pathogenesis of schizophrenia in the Han Chinese population. Further studies are needed to establish the biological context and potential clinical utility of these findings.

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