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Connecting myelin-related and synaptic dysfunction in schizophrenia with SNP-rich gene expression hubs

View Article: PubMed Central - PubMed

ABSTRACT

35 times32 times: Combining genome-wide mapping of SNP-rich regions in schizophrenics and gene expression data in all brain compartments across the human life span revealed that genes with promoters most frequently mutated in schizophrenia are expression hubs interacting with far more genes than the rest of the genome. We summed up the differentially methylated “expression neighbors” of genes that fall into one of 108 distinct schizophrenia-associated loci with high number of SNPs. Surprisingly, the number of expression neighbors of the genes in these loci were higher for the positively correlating genes ( higher for the negatively correlating ones) than for the rest of the ~16000 genes. While the genes in the 108 loci have little known impact in schizophrenia, we identified many more known schizophrenia-related important genes with a high degree of connectedness (e.g. MOBP, SYNGR1 and DGCR6), validating our approach. Both the most connected positive and negative hubs affected synapse-related genes the most, supporting the synaptic origin of schizophrenia. At least half of the top genes in both the correlating and anti-correlating categories are cancer-related, including oncogenes (RRAS and ALDOA), providing further insight into the observed inverse relationship between the two diseases.

No MeSH data available.


Boxplots of inteacting partners for all genes and promoter-selected and cis-selected genes in 108 SNP-rich genomic regions taken from ref. 7.(A) Positive, (B) negative correlating partners.
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f1: Boxplots of inteacting partners for all genes and promoter-selected and cis-selected genes in 108 SNP-rich genomic regions taken from ref. 7.(A) Positive, (B) negative correlating partners.

Mentions: Counting the positively and negatively correlating partners for all the genes except in the 108 loci in ref. 7 resulted in a median number of 71 positively and 63 negatively correlating pairs, respectively (Fig. 1). Unexpectedly, the median numbers of correlating pairs for the promoter-selected genes were 2472 and 2013, corresponding to a 35-fold and 32-fold increase for the positive and negative pairs, respectively.


Connecting myelin-related and synaptic dysfunction in schizophrenia with SNP-rich gene expression hubs
Boxplots of inteacting partners for all genes and promoter-selected and cis-selected genes in 108 SNP-rich genomic regions taken from ref. 7.(A) Positive, (B) negative correlating partners.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5382542&req=5

f1: Boxplots of inteacting partners for all genes and promoter-selected and cis-selected genes in 108 SNP-rich genomic regions taken from ref. 7.(A) Positive, (B) negative correlating partners.
Mentions: Counting the positively and negatively correlating partners for all the genes except in the 108 loci in ref. 7 resulted in a median number of 71 positively and 63 negatively correlating pairs, respectively (Fig. 1). Unexpectedly, the median numbers of correlating pairs for the promoter-selected genes were 2472 and 2013, corresponding to a 35-fold and 32-fold increase for the positive and negative pairs, respectively.

View Article: PubMed Central - PubMed

ABSTRACT

35 times32 times: Combining genome-wide mapping of SNP-rich regions in schizophrenics and gene expression data in all brain compartments across the human life span revealed that genes with promoters most frequently mutated in schizophrenia are expression hubs interacting with far more genes than the rest of the genome. We summed up the differentially methylated “expression neighbors” of genes that fall into one of 108 distinct schizophrenia-associated loci with high number of SNPs. Surprisingly, the number of expression neighbors of the genes in these loci were higher for the positively correlating genes ( higher for the negatively correlating ones) than for the rest of the ~16000 genes. While the genes in the 108 loci have little known impact in schizophrenia, we identified many more known schizophrenia-related important genes with a high degree of connectedness (e.g. MOBP, SYNGR1 and DGCR6), validating our approach. Both the most connected positive and negative hubs affected synapse-related genes the most, supporting the synaptic origin of schizophrenia. At least half of the top genes in both the correlating and anti-correlating categories are cancer-related, including oncogenes (RRAS and ALDOA), providing further insight into the observed inverse relationship between the two diseases.

No MeSH data available.