Poster Presentation GENEMAPPERS 2026

Genetic Links Between Cortical Brain Morphometry and Suicide Ideation and Suicide Attempt Risk in Children and Adults (#69)

Zuriel Ceja 1 2 , Nathaniel Thomas 3 , Jill A Rabinowitz 3 4 , Nick Martin 1 2 , Sarah E Medland 1 2 , Alexis C Edwards 5 , Miguel E Rentería 1 2 , Luis M García-Marín 1 2
  1. Brain & Mental Health Program, QIMR Berghofer Medical Research Institut, Brisbane, QLD, 4006, Australia
  2. School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, QLD, 4072, Australia.
  3. Department of Psychiatry, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854, USA
  4. Rutgers Addiction Research Center, Brain Health Institute, Rutgers University, Piscataway, NJ 08854, USA
  5. Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Richmond, VA USA

Background:

Suicidal thoughts and behaviours (STBs), including suicide ideation (SI) and suicide attempt (SA), are leading global causes of mortality. Neuroimaging studies have implicated cortical alterations in STBs; however, the shared genetic architecture of these alterations remains unclear. 

 

Methods:

We leveraged GWAS summary statistics for SI (N = 438,849), SA (N = 815,178), and cortical brain morphometry (N = 51,665). Genome-wide and local genetic correlations were estimated via Linkage Disequilibrium Score Regression (LDSC) and GWAS-pairwise. Gene-level associations were performed using MAGMA under pooled and per-phenotype FDR frameworks. Polygenic scores (PGS) for SI and SA were tested for associations with baseline and change in cortical morphometry (ages 9–16) in the Adolescent Brain Cognitive Development study.

 

Results:

At the local level, 24 unique genomic segments were associated with both SA and cortical traits, primarily in the caudal/rostral anterior cingulate and superior/transverse temporal cortices, and two for SI and cortical measures. Gene-based analyses revealed associations of MAPRE3/EB3 and CGREF1 with SA and mean cortical thickness after multiple-testing correction. Nominally (P < 0.05), 103 genes were associated with SA and four with SI. These genes were enriched for synaptic and neurodevelopmental pathways. SA PGS were negatively associated with precentral gyrus thickness and volume, pars opercularis thickness, and inferior temporal gyrus volume. Change in the volume of the inferior parietal cortex over time varied across SI PGS, with higher SI PGS corresponding to an increased rate of change over time.

 

Conclusion:

Our findings suggest that STBs share genetic influences with cortical brain morphometry, particularly across fronto-cingulo-temporal networks, central to emotion regulation, self-referential processing, and social cognition. MAPRE3 and CGREF1 highlight complementary biological mechanisms, while broader nominal associations reinforce polygenic contributions of synaptic, developmental, and epigenomic processes. Distinct SI- and SA-PGS associations suggest divergent neurogenetic pathways of suicide risk emerging early in development.