Genetic Studies of Schizophrenia to Date Fail to Find Anything of Substance

 This Study compiles the results of genetic studies (GWAS) for Schizophrenia to date:

What genes are differentially expressed in individuals with schizophrenia? A systematic review (Merikangas et al.)

Despite the authors' claim that the review is "promising," it provides nothing of substance. Below are some excerpts. 

First they review the problem to date:

Though there have been more than 300 studies of gene expression in schizophrenia over the past 15 years, none of the studies have yielded consistent evidence for specific genes that contribute to schizophrenia risk. The aim of this work is to conduct a systematic review and synthesis of case–control studies of genome-wide gene expression in schizophrenia. 

There have been more than three hundred studies of gene expression in schizophrenia over the past 15 years, but to date there is no consistent evidence for clearly implicated genes from these findings.

Here are some of their findings: 

Of the top 160 genes, the majority of replicated findings were inconsistent in their reported direction of effect (n = 108 genes). This finding did not appear to follow a pattern based on the origin tissue or the expression measurement technology employed 

The GBP2 gene, which appeared in five studies, was reported to be upregulated in individuals with schizophrenia in four studies and downregulated in one. Of the 21 genes reported as significant by four studies, 19 had inconsistent directions of effect. Of the 138 genes that appeared in three studies, 88 had the inconsistent direction of effect.

In other words, even when they purported to find the same gene in more than one study, it is correlated higher or lower for that gene from one study to the next, suggesting random false positive findings. 

Of the 160 genes reported as significantly differentially expressed in three or more studies, none showed associations with rare variants in the SCHEMA data after correction for multiple comparisons. 

 

This review summarizes the literature on gene expression in schizophrenia and demonstrates the surprisingly small overlap in the genes reported across studies. Only 26 studies met our a priori inclusion criteria and were described here. The results of this review were unexpected, in that few genes were found in more than three studies, and the reported direction of effect was so variable. It was hoped that gene expression would help to explain the large number of genome-wide associated variants that are not found in genes and are theorized to be regulatory. With some exceptions described below, gene expression does not implicate the same genes that have been found by GWAS, CNV studies, or exome studies via SCHEMA.

As we would expect, the genes found in this study appear to be differentially expressed in the brain when compared to other body tissues. However, there are some unexpected results; notably, differential expression in the pancreas, subcutaneous adipose tissue, whole blood, liver, and lymphocytes. It is possible that the differential expression in blood, brain, and lymphocytes is due in some part to these being the tissues assayed in the transcriptome abundance studies summarized here.