Abstract
Recent genetic studies for suicidality, including four independent GWAS, have not reproduced each other’s top implicated genes. While arguments of heterogeneity, methodology, and sample sizes can be invoked, heterogeneity is a feature, not a “bug” (as is well understood in biology and in personalized medicine). A comprehensive body of work on blood biomarkers for suicidality has previously been published by our group. We examine the issue of reproducibility using these different approaches, and provide reassuring evidence for convergence of findings, as well as some generalizable insights.
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References
Niculescu AB, Levey DF, Phalen PL, Le-Niculescu H, Dainton HD, Jain N, et al. Understanding and predicting suicidality using a combined genomic and clinical risk assessment approach. Mol Psychiatry. 2015;20:1266–85.
Levey DF, Niculescu EM, Le-Niculescu H, Dainton HL, Phalen PL, Ladd TB, et al. Towards understanding and predicting suicidality in women: biomarkers and clinical risk assessment. Mol Psychiatry. 2016;21:768–85.
Niculescu AB, Le-Niculescu H, Levey DF, Phalen PL, Dainton HL, Roseberry K, et al. Precision medicine for suicidality: from universality to subtypes and personalization. Mol Psychiatry. 2017;22:1250–73.
Stein MB, Ware EB, Mitchell C, Chen CY, Borja S, Cai T, et al. Genomewide association studies of suicide attempts in US soldiers. Am J Med Genet Part B, Neuropsychiatr Genet. 2017;174:786–97.
Kimbrel NA, Garrett ME, Dennis MF, Va Mid-Atlantic Mental Illness Research E, Clinical Center W, Hauser MA, et al. A genome-wide association study of suicide attempts and suicidal ideation in U.S. military veterans. Psychiatry Res. 2018;269:64–69.
Erlangsen A, Appadurai V, Wang Y, Turecki G, Mors O, Werge T, et al. Genetics of suicide attempts in individuals with and without mental disorders: a population-based genome-wide association study. Mol Psychiatry. 2018. https://doi.org/10.1038/s41380-018-0218-y. [Epub ahead of print].
Levey DF, Polimanti R, Cheng Z, Zhou H, Nunez YZ, Jain S, et al. Genetic associations with suicide attempt severity and genetic overlap with major depression. Transl Psychiatry. 2019;9:22.
Coon H, Darlington TM, DiBlasi E, Callor WB, Ferris E, Fraser A, et al. Genome-wide significant regions in 43 Utah high-risk families implicate multiple genes involved in risk for completed suicide. Mol Psychiatry. 2018. https://doi.org/10.1038/s41380-018-0282-3. [Epub ahead of print].
Sokolowski M, Wasserman J, Wasserman D. Gene-level associations in suicide attempter families show overrepresentation of synaptic genes and genes differentially expressed in brain development. Am J Med Genet Part B, Neuropsychiatr Genet. 2018;177:774–84.
Niculescu AB, Levey D, Le-Niculescu H, Niculescu E, Kurian SM, Salomon D. Psychiatric blood biomarkers: avoiding jumping to premature negative or positive conclusions. Mol Psychiatry. 2015;20:286–8.
Ayalew M, Le-Niculescu H, Levey DF, Jain N, Changala B, Patel SD, et al. Convergent functional genomics of schizophrenia: from comprehensive understanding to genetic risk prediction. Mol Psychiatry. 2012;17:887–905.
Acknowledgements
This work is, in essence, a field-wide collaboration. We would like to acknowledge our debt of gratitude for the efforts and results of the multiple other groups, cited in our paper, who have conducted and published genetic studies in suicidality. With their arduous and careful work, a convergent approach such as ours is possible. We would also like to acknowledge the contribution of the members of group over the years, in particular our students Dan Levey, Peter Phalen, and Kyle Roseberry, and that of our collaborators on the suicide biomarker studies, in particular George Sandusky, Mike Yard, and Sunil Kurian. This work was supported by an NIH Directors’ New Innovator Award (1DP2OD007363) and a VA Merit Award (2I01CX000139) to ABN.
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ABN designed the analyses and wrote the manuscript. HLN analyzed the datasets. Both authors reviewed the final manuscript and agreed with it.
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ABN is listed as inventor on a patent application being filed by Indiana University, and is a co-founder of MindX Sciences. The other author declares that he has no conflict of interest.
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Niculescu, A.B., Le-Niculescu, H. Convergence of recent GWAS data for suicidality with previous blood biomarkers: independent reproducibility using independent methodologies in independent cohorts. Mol Psychiatry 25, 19–21 (2020). https://doi.org/10.1038/s41380-019-0465-6
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DOI: https://doi.org/10.1038/s41380-019-0465-6