Associations between Suicidal Thoughts and Behaviors and Genetic Liability for Cognitive Performance, Depression, and Risk-Taking in a High-Risk Sample

Emma C Johnson; Fazil Aliev; Jacquelyn L Meyers; Jessica E Salvatore; Rebecca Tillman; Yoonhoo Chang; Anna R Docherty; Ryan Bogdan; Laura Acion; Grace Chan; David B Chorlian; Chella Kamarajan; Samuel Kuperman; Ashwini Pandey; Martin H Plawecki; Marc Schuckit; Jay Tischfield; Howard J Edenberg; Kathleen K Bucholz; John I Nurnberger; Bernice Porjesz; Victor Hesselbrock; Danielle M Dick; John R Kramer; Arpana Agrawal

doi:10.1159/000517169

Associations between Suicidal Thoughts and Behaviors and Genetic Liability for Cognitive Performance, Depression, and Risk-Taking in a High-Risk Sample

Complex Psychiatry. 2021 Aug;7(1-2):34-44. doi: 10.1159/000517169. Epub 2021 May 18.

Authors

Emma C Johnson¹, Fazil Aliev², Jacquelyn L Meyers^{3

4}, Jessica E Salvatore², Rebecca Tillman¹, Yoonhoo Chang¹, Anna R Docherty⁵, Ryan Bogdan⁶, Laura Acion⁷, Grace Chan⁸, David B Chorlian³, Chella Kamarajan^{3

4}, Samuel Kuperman⁹, Ashwini Pandey³, Martin H Plawecki¹⁰, Marc Schuckit¹¹, Jay Tischfield¹², Howard J Edenberg^{13

14}, Kathleen K Bucholz¹, John I Nurnberger^{10

13}, Bernice Porjesz^{3

4}, Victor Hesselbrock⁸, Danielle M Dick^{2

15}, John R Kramer⁹, Arpana Agrawal¹

Affiliations

¹ Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.
² Department of Psychology, Virginia Commonwealth University, Richmond, Virginia, USA.
³ Department of Psychiatry, SUNY Downstate Health Sciences University, Brooklyn, New York, USA.
⁴ Henri Begleiter Neurodynamics Lab, SUNY Downstate Health Sciences University, Brooklyn, New York, USA.
⁵ Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, Utah, USA.
⁶ Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, Missouri, USA.
⁷ Calculus Institute, University of Buenos Aires, Buenos Aires, Argentina.
⁸ Department of Psychiatry, University of Connecticut School of Medicine, Farmington, Connecticut, USA.
⁹ Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
¹⁰ Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana, USA.
¹¹ Department of Psychiatry, University of California San Diego, San Diego, California, USA.
¹² Department of Genetics, Rutgers University, Piscataway, New Jersey, USA.
¹³ Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
¹⁴ Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
¹⁵ Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia, USA.

Abstract

Background: Suicidal thoughts and behaviors (STBs) and nonsuicidal self-injury (NSSI) behaviors are moderately heritable and may reflect an underlying predisposition to depression, impulsivity, and cognitive vulnerabilities to varying degrees.

Objectives: We aimed to estimate the degrees of association between genetic liability to depression, impulsivity, and cognitive performance and STBs and NSSI in a high-risk sample.

Methods: We used data on 7,482 individuals of European ancestry and 3,359 individuals of African ancestry from the Collaborative Study on the Genetics of Alcoholism to examine the links between polygenic scores (PGSs) for depression, impulsivity/risk-taking, and cognitive performance with 3 self-reported indices of STBs (suicidal ideation, persistent suicidal ideation defined as ideation occurring on at least 7 consecutive days, and suicide attempt) and with NSSI.

Results: The PGS for depression was significantly associated with all 4 primary self-harm measures, explaining 0.6-2.5% of the variance. The PGS for risk-taking behaviors was also associated with all 4 self-harm behaviors in baseline models, but was no longer associated after controlling for a lifetime measure of DSM-IV alcohol dependence and abuse symptom counts. Polygenic predisposition for cognitive performance was negatively associated with suicide attempts (q = 3.8e-4) but was not significantly associated with suicidal ideation nor NSSI. We did not find any significant associations in the African ancestry subset, likely due to smaller sample sizes.

Conclusions: Our results encourage the study of STB as transdiagnostic outcomes that show genetic overlap with a range of risk factors.

Keywords: Cognitive function; Depression; GWAS; Impulsivity; Polygenic risk scores; Suicide.

Abstract

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