Rare CNVs and Tag SNPs at 15q11.2 are associated with schizophrenia in the Han Chinese population
Open accessAbstract
BACKGROUND: Rare copy number variations (CNVs) were involved in the etiology of neuropsychiatric disorders, and some of them appeared to be shared risk factors for several different diseases. One of those promising loci is the CNV at 15q11.2, including 4 genes, TUBGCP5, CYFIP1, NIPA2, and NIPA1. Several studies showed that microdeletions at this locus were significant associated with schizophrenia. In the current study, we investigated the role of both rare CNVs and common single nucleotide polymorphisms (SNPs) at 15q11.2 in schizophrenia in the Chinese Han population. METHODS: We screened deletions at 15q11.2 in 2058 schizophrenia patients and 3275 normal controls in Chinese Han population by Affymetrix 500K/6.0 SNP arrays and SYBR green real-time polymerase chain reaction and then validated deletions by multiplex ligation-dependent probe amplification and Taqman real-time assays. We successfully genotyped 27 tag SNPs in total and tested associations in 1144 schizophrenia cases and 1144 normal controls. RESULTS: We found a triple increase of deletions in cases over controls, with OR=4.45 (95% CI=1.36-14.60) and P=.014. In the analysis of common SNPs, we found that the most significant SNP in schizophrenia was rs4778334 (OR=.72, 95% CI=0.60-0.87, allelic P=.0056 after permutation, genotypic P=.015 after permutation). We also found SNP rs1009153 in CYFIP1 was associated with schizophrenia (OR=0.82, 95% CI=0.73-0.93, allelic P=.044 after permutation). CONCLUSION: We found that both rare deletions and common variants at 15q11.2 were associated with schizophrenia in the Chinese Han population.
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Two common SNPs in CYFIP1 are associated with schizophrenia.
“Following the association of two common SNPs in CYFIP1 in SCZ patients110 (Table 2j), the compound heterozygous variants p.Ile476Val and p.Pro742Leu were identified via exome sequencing in two affected males from a family, who exhibited DD, ID, ASD, epilepsy, and an absence of speech (Table 2k).”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [110]
The Associations Between Tag SNPs and Schizophrenia section reports an association for one common CYFIP1 SNP, rs1009153. Table 3 lists the other SNP that remained significant after permutation, rs4778334, between NIPA2 and NIPA1—not in CYFIP1. The claim's count of two CYFIP1 SNPs is therefore unsupported. (LLM, conf=0.92)
Experimental — accuracy not yet measuredThe CYFIP1/SRA1 gene is located in a chromosomal region linked to various neurological disorders, including intellectual disability, autism, and schizophrenia.
“The CYFIP1/SRA1 gene is located in a chromosomal region linked to various neurological disorders, including intellectual disability, autism, and schizophrenia.”
From CYFIP1 Coordinates mRNA Translation and Cytoskeleton Remodeling to Ensure Proper Dendritic Spine Formation (2013) · cites this paper as Zhao et al., 2012
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“Further, associations between schizophrenia and mutations in CYFIP1 altering mRNA levels have also been reported (21–24).”
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Influential
- Authors
- Zhao, Q., Li, T., Zhao, X., Huang, K., Wang, T., Li, Z., Ji, J., Zeng, Z., Zhang, Z., Li, K., Feng, G., St Clair, D., He, L., & Shi, Y.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Fudan University (CN)
- East China University of Science and Technology (CN)
- Shanghai Mental Health Center (CN)
- Corresponding author
- Shi, YongYong
- Venue
- Schizophrenia Bulletin
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-02-08
- Volume
- 39
- Issue
- 3
- Pages
- 712-719
- ISSN
- 0586-7614 (ISSN-L)
- 1745-1701
- PMC
- PMC3627771
- OpenAlex
- W2154136432
- Cited by
- 58
- References
- 7
- Citations by year
- 2026: 1 · 2025: 3 · 2023: 5 · 2022: 4 · 2021: 5 · 2020: 6 · 2019: 5 · 2018: 5 · 2017: 5 · 2016: 5 · 2015: 1 · 2014: 6 · 2013: 5 · 2012: 2
- FWCI
- 2.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Schizophrenia Bulletin (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (R01AA022701)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- schizophrenia, copy number variation
- MeSH terms
- Adult, Base Sequence, Chromosomes, Human, Pair 15, Female, Humans, Male, Membrane Proteins, Microtubule-Associated Proteins, Schizophrenia, Case-Control Studies, Sequence Deletion, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Cation Transport Proteins, Asian People, Adaptor Proteins, Signal Transducing, Young Adult, DNA Copy Number Variations, Multiplex Polymerase Chain Reaction, Real-Time Polymerase Chain Reaction
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