Overlapping genetic effects between suicidal ideation and neurocognitive functioning

• Authors: Leslie Brick, Emory University; Maria E. Marraccini, University of North Carolina; Lauren Micalizzi, Emory University; Chelsie E. Benca-Bachman, Emory University; Valerie S. Knopik, Purdue University; Rohan Palmer, Emory University
• Journal Title: Journal of Affective Disorders
• Volume: Volume 249
• Publisher: Elsevier | 2019-04-15, Pages 104-111
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.jad.2019.02.003
• Subjects: Biology, Genetics; Biology, Neuroscience; Psychology, Cognitive; Sociology, Public and Social Welfare
• Keywords: Genetics; Heritability; Memory; Neurocognitive functioning; Suicidal ideation; Adolescent; Child; Cohort Studies; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Male; Neurocognitive Disorders; Polymorphism, Single Nucleotide; Quantitative Trait, Heritable; Suicidal Ideation; Young Adult

Abstract

Background: Suicide is the second leading cause of death among adolescents and young adults. Several studies have indicated significant genetic influences on suicide-related phenotypes and mounting evidence from neurobiological research has linked deficits in neurocognitive abilities to suicide phenotypes. The goal of the present study was to estimate the heritability of suicidal ideation (SI) in a large sample of adolescents and determine if SI is genetically correlated with neurocognitive functioning. Methods: Genome-wide data (N = 3564 unrelated individuals of European Ancestry) were drawn from the Philadelphia Neurodevelopment Cohort. Adolescents completed a psychiatric assessment, as well as a computerized neurocognitive battery to assess performance across four domains: memory, executive function, social cognition, and complex cognition. Genomic-relatedness-matrix restricted maximum likelihood (GREML) estimation was used to determine SNP-heritability (h 2SNP ) of SI and the genetic correlation (r G ) between SI and neurocognitive domains. Results: Nearly 17% of adolescents reported SI. The SNP-heritability estimate for SI was marginally significant (h 2SNP = 11%, SE = 8%, p = 0.086). Bivariate analyses indicated a significant r G between SI and emotion identification (r G = 0.79, SE = 0.45, p = 0.006; phenotypic correlation r = 0.04, p = 0.017). Limitations: It is possible that SI may represent a related, but differentially heritable construct from suicide attempts/completion and other comorbid psychopathology. Additionally, though genetic correlations point to shared genetic factors across traits, direct causal mechanisms cannot be deduced. Conclusions: Common heritable factors contribute to variation in SI and neurocognitive functioning. Genetic factors influencing emotion identification have significant genetic overlap with SI.