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Try, Try, and Try Again: Complicating the Genetic Mechanisms of Schizophrenia

Working alongside researchers from the Institute of Mental Health at the Second Xiangya Hospital, Ph.D candidate MA Liang and his colleagues of the Key Laboratory of Animal Models and Human Disease Mechanisms at the Kunming Institute of Zoology, Chinese Academy of Sciences (KIZ, CAS) are working to better understand genetic risk factors associated schizophrenia in Han Chinese.

Despite years of work and strong indications that schizophrenia is a highly heritable psychiatric disorder, the precise mechanisms and risk factors for the disease are still poorly understood. Two recent genome-wide studies on Han Chinese found a total of nine single-nucleotide polymorphisms (SNPs) that may be involved with schizophrenia, but neither found risk loci that overlapped with one another. 

To verify either or both studies’ findings, MA et al conducted a follow-up validation study. After analyzing genetic data of nearly 1000 schizophrenic Han Chinese from Hunan Province, they found no association between the disease and any of the suggested SNPs. In fact, they found no significant genetic differences at all between their control group and patients with schizophrenia.

These results were not unexpected, especially since the original studies did not share any of the same conclusions. MA et al were quick to point out that regional variation may play a strong role in the failure to validate the earlier findings, citing that there is likely a high genetic heterogeneity in people who suffer from schizophrenia and that the mechanisms for schizophrenia are simply more complicated. A large amount of smaller variations may be the cause or gene interactions with the environment. 

Despite the inability to validate the earlier genome-wide studies and the narrow scope of their own experiments, MA et al are hopeful that more studies of this type will contribute to the meta-analysis of schizophrenia and continue to offer new insights. The important question arising from this study is whether or not the scientific community has the courage to continually perform validation studies in the search for the more subtle mechanisms that underlie schizophrenia.

The full report “Evaluating risk loci for schizophrenia distilled from genome-wide association studies in Han Chinese from central China” can be found as a letter to the editor in the upcoming issue of Molecular Psychiatry 17(6) or as an e-publication ahead of print at:

This study was supported by the National Natural Science Foundation of China, Yunnan Province, the Chinese Academy of Sciences and the National Key Basic Research and Development Program.


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