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DISCovery in psychiatric genetics

Molecular Psychiatry volume 19, page 145 (2014)Cite this article

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The Guest Editorial by Sullivan1 on DISC1 reflects not only his limitations in understanding biology, but more broadly reflects those of a group of statistically trained non-biologists who are currently very active (and vocal) in psychiatric genetics. Illness works through alterations in biology. Biology works at a gene level and not at a single-nucleotide polymorphism (SNP) level. Biologically important genes such as DISC1 (or BDNF or COMT) have more SNP heterogeneity and diversity in the population2 likely owing to the need to evolutionarily adapt and fine-tune the interface between organism and environment.3 Integrative approaches at a gene level clearly demonstrate their involvement and show reproducibility4 as opposed to the statistically driven SNP-focused Genome-Wide Association Study (GWAS) approaches of Sullivan and colleagues5 that have identified primarily housekeeping genes to date (such as ANK3, CACNA1C and ODZ). In fact, SNP-focused GWAS approaches miss the boat on their own data. The overlap between GWAS studies is 100-fold greater at a gene level than at a nominally significant SNP level4. Moreover, what non-biologists do not understand is how the brain (or for the matter, the body) works. Schizophrenia, like other complex disorders, is a broad entity overlapping with other disorders. Genes and their products are building blocks that in different combinations, and in different environmental contexts, give different psychiatric and non-psychiatric syndromes. In the sporting tradition of years past in science, before things became rather boring and politically correct, I would like to wager with Sullivan1 the following: whomever is wrong between the two of us on this subject should write a Letter to Molecular Psychiatry in 2020, titled Mea Culpa on DISC1.

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References

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  1. Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA

    A B Niculescu III

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  1. A B Niculescu III
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Correspondence to A B Niculescu III.

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Niculescu, A. DISCovery in psychiatric genetics. Mol Psychiatry 19, 145 (2014). https://doi.org/10.1038/mp.2013.176

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