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Significant shared heritability underlies suicide attempt and clinically predicted probability of attempting suicide

View ORCID ProfileDouglas M. Ruderfer, Colin G. Walsh, Matthew W. Aguirre, Jessica D. Ribeiro, Joseph C. Franklin, Manuel A. Rivas
doi: https://doi.org/10.1101/266411
Douglas M. Ruderfer
1.Division of Genetic Medicine, Departments of Medicine and Psychiatry, Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN USA
2.Department of Biomedical Informatics. Vanderbilt University Medical Center, Nashville, TN USA
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  • ORCID record for Douglas M. Ruderfer
Colin G. Walsh
2.Department of Biomedical Informatics. Vanderbilt University Medical Center, Nashville, TN USA
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Matthew W. Aguirre
3.Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA USA
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Jessica D. Ribeiro
4.Department of Psychology, Florida State University, Tallahassee, FL USA
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Joseph C. Franklin
4.Department of Psychology, Florida State University, Tallahassee, FL USA
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Manuel A. Rivas
3.Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA USA
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Abstract

Suicide accounts for nearly 800,000 deaths per year worldwide with rates of both deaths and attempts rising. Family studies have estimated substantial heritability of suicidal behavior; however, collecting the sample sizes necessary for successful genetic studies has remained a challenge. We utilized two different approaches in independent datasets to characterize the contribution of common genetic variation to suicide attempt. The first is a patient reported suicide attempt phenotype from genotyped samples in the UK Biobank (337,199 participants, 2,433 cases). The second leveraged electronic health record (EHR) data from the Vanderbilt University Medical Center (VUMC, 2.8 million patients, 3,250 cases) and machine learning to derive probabilities of attempting suicide in 24,546 genotyped patients. We identified significant and comparable heritability estimates of suicide attempt from both the patient reported phenotype in the UK Biobank (h2SNP = 0.035, p = 7.12×10−4) and the clinically predicted phenotype from VUMC (h2SNP = 0.046, p = 1.51×10−2). A significant genetic overlap was demonstrated between the two measures of suicide attempt in these independent samples through polygenic risk score analysis (t = 4.02, p = 5.75×10−5) and genetic correlation (rg = 1.073, SE = 0.36, p = 0.003). Finally, we show significant but incomplete genetic correlation of suicide attempt with insomnia (rg = 0.34 - 0.81) as well as several psychiatric disorders (rg = 0.26 - 0.79). This work demonstrates the contribution of common genetic variation to suicide attempt. It points to a genetic underpinning to clinically predicted risk of attempting suicide that is similar to the genetic profile from a patient reported outcome. Lastly, it presents an approach for using EHR data and clinical prediction to generate quantitative measures from binary phenotypes that improved power for our genetic study.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted February 15, 2018.
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Significant shared heritability underlies suicide attempt and clinically predicted probability of attempting suicide
Douglas M. Ruderfer, Colin G. Walsh, Matthew W. Aguirre, Jessica D. Ribeiro, Joseph C. Franklin, Manuel A. Rivas
bioRxiv 266411; doi: https://doi.org/10.1101/266411
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Significant shared heritability underlies suicide attempt and clinically predicted probability of attempting suicide
Douglas M. Ruderfer, Colin G. Walsh, Matthew W. Aguirre, Jessica D. Ribeiro, Joseph C. Franklin, Manuel A. Rivas
bioRxiv 266411; doi: https://doi.org/10.1101/266411

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