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A Novel Relationship for Schizophrenia, Bipolar, and Major Depressive Disorder. Part 8: a Hint from Chromosome 8 High Density Association Screen

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Abstract

Convergent evidence from genetics, symptomatology, and psychopharmacology implies that there are intrinsic connections between schizophrenia (SCZ), bipolar disorder (BPD), and major depressive disorder (MDD); for example, any two or even three of these disorders could co-exist in some families. A total of 48,753 single nucleotide polymorphisms (SNPs) on chromosome 8 were genotyped by Affymetrix Genome-Wide Human SNP array 6.0 on 119 SCZ, 253 BPD (type I), 177 MDD patients, and 1000 controls. Associated SNP loci were comprehensively revealed, and outstanding susceptibility genes were identified including CSMD1, NRG1, PXDNL, SGCZ, and TMEM66. Unexpectedly, flanking genes for up to 95.9 % of the associated SNPs were replicated (P ≤ 9.9E−8) in the enlarged cohort of 986 SCZ patients. Considering convergent evidence, our results implicate that bipolar disorder and major depressive disorder might be subtypes of schizophrenia.

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Acknowledgments

We would like to thank all of the patients and controls who participated in this study.

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Authors and Affiliations

  1. Department of Medical Genetics, Institute of Basic Medicine, Shandong Academy of Medical Sciences, 18877 Jingshi Road, Jinan, 250062, Shandong, People’s Republic of China

    Xing Chen, Feng Long, Lizeng Qin & Gang Chen

  2. CapitalBio Corporation, 18 Life Science Parkway, Changping District, Beijing, 102206, People’s Republic of China

    Bin Cai & Xiaohong Chen

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  1. Xing Chen
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  2. Feng Long
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  3. Bin Cai
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  4. Xiaohong Chen
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Corresponding author

Correspondence to Gang Chen.

Ethics declarations

Written consent was obtained from all subjects or legally authorized representative consented on the behalf of participants. This study was approved by the Ethics Committee of the Institute of Basic Medicine of Shandong Academy of Medical Sciences.

Financial Disclosures

This study was supported by grants from the Natural Science Foundation of Shandong Province (Grant Nos. ZR2013HM078, Z2008C11, Z2004C10), the Shandong Province Science and Technology Development Plan (Grant No. 2011GSF11821), the National High-tech R&D Program of China (863 Program Grant No. 2002AA223021), The National Natural Science Foundation of China (Grant Nos. 30770780, 30440042), Ministry of Human Resources and Social Security of China (Grant No. 2009.416), the Department of Science and Technology of Shandong Province (Grant No. 2008GG27C01011-8), the National Bureau of Foreign Experts Affairs (Grant No. CG2006370002), the Shandong Bureau of Foreign Experts Affairs (Grant No. L20063700407, and the Shandong Academy of Medical Sciences Grant Nos. 2012-25, 2009-15).

Conflict of Interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

ESM 1

The P- value plot of of single nucleotide polymorphisms (SNPs) on Chromosome 8 from the the analysis of 119 schizophrenia (SCZ) patients and 1000 controls in a Genome-wide Association Study by Affymetrix Genome-Wide Human SNP array 6.0 in the population of Shandong province of China. (DOCX 145 kb)

ESM 2

The P- value plot of of single nucleotide polymorphisms (SNPs) on Chromosome 8 from the the analysis of 253 bipolar disorder (BPD) patients and 1000 controls in a Genome-wide Association Study by Affymetrix Genome-Wide Human SNP array 6.0 in the population of Shandong province of China. (DOCX 152 kb)

ESM 3

The P- value plot of of single nucleotide polymorphisms (SNPs) on Chromosome 8 from the the analysis of 177 major depressive disorder (MDD) patients and 1000 controls in a Genome-wide Association Study by Affymetrix Genome-Wide Human SNP array 6.0 in the population of Shandong province of China. (DOCX 148 kb)

ESM 4

(XLSB 2129 kb)

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Chen, X., Long, F., Cai, B. et al. A Novel Relationship for Schizophrenia, Bipolar, and Major Depressive Disorder. Part 8: a Hint from Chromosome 8 High Density Association Screen. Mol Neurobiol 54, 5868–5882 (2017). https://doi.org/10.1007/s12035-016-0102-1

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  • DOI: https://doi.org/10.1007/s12035-016-0102-1

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