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Article summary:

1. Schizophrenia has a substantial genetic component, with contributions from both common and rare variants.

2. The Schizophrenia Exome Sequencing Meta-Analysis (SCHEMA) consortium analyzed exome sequence data from 24,248 individuals with schizophrenia and 97,322 controls from seven continental populations to identify ten genes with ultra-rare coding variants that confer substantial risk for schizophrenia.

3. This study provides evidence that common coding variants and ultra-rare variants identify an overlapping set of genes and suggests that increased scale following this approach will uncover additional risk genes and help complete the genetic architecture of schizophrenia.

Article analysis:

The article "Rare coding variants in ten genes confer substantial risk for schizophrenia" published in Nature discusses the results of a large-scale sequencing study aimed at identifying rare genetic variants associated with schizophrenia. The study identified ten genes with ultra-rare coding variants that confer substantial risk for schizophrenia, providing new insights into the molecular etiology of this complex psychiatric disorder.

The article provides a comprehensive overview of the study design, data analysis, and key findings. It highlights the challenges associated with identifying rare genetic variants that contribute to disease risk and emphasizes the importance of large-scale collaborative efforts to overcome these challenges.

One potential bias in the article is its focus on rare coding variants as a primary driver of schizophrenia risk. While these variants are undoubtedly important, it is also important to consider other factors such as environmental exposures, epigenetic modifications, and gene-environment interactions that may contribute to disease risk.

Another potential bias is the emphasis on gene discovery as a means of advancing therapeutic development for schizophrenia. While identifying specific genes and pathways involved in disease pathogenesis is certainly an important step towards developing targeted therapies, it is also important to consider broader approaches such as network-based analyses and systems biology approaches that take into account the complex interactions between multiple genes and pathways.

Overall, while the article provides valuable insights into the genetics of schizophrenia, it is important to approach these findings with caution and recognize their limitations. Further research is needed to fully understand the complex etiology of this disorder and develop effective treatments that address its diverse symptoms and underlying mechanisms.