@article{ref1,
title="Effects of polygenic risk for suicide attempt and risky behavior on brain structure in young people with familial risk of bipolar disorder",
journal="American journal of medical genetics. part B, neuropsychiatric genetics",
year="2021",
author="Overs, Bronwyn J. and Roberts, Gloria and Ridgway, Kate and Toma, Claudio and Hadzi-Pavlovic, Dusan and Wilcox, Holly C. and Hulvershorn, Leslie A. and Nurnberger, John I. and Schofield, Peter R. and Mitchell, Philip B. and Fullerton, Janice M.",
volume="ePub",
number="ePub",
pages="ePub-ePub",
abstract="Bipolar disorder (BD) is associated with a 20-30-fold increased suicide risk compared to the general population. First-degree relatives of BD patients show inflated rates of psychopathology including suicidal behaviors. As reliable biomarkers of suicide attempts (SA) are lacking, we examined associations between suicide-related polygenic risk scores (PRSs)-a quantitative index of genomic risk-and variability in brain structures implicated in SA. Participants (n = 206; aged 12-30 years) were unrelated individuals of European ancestry and comprised three groups: 41 BD cases, 96 BD relatives (&quot;high risk&quot;), and 69 controls. Genotyping employed PsychArray, followed by imputation. Three PRSs were computed using genome-wide association data for SA in BD (SA-in-BD), SA in major depressive disorder (SA-in-MDD) (Mullins et al., 2019, The American Journal of Psychiatry, 176(8), 651-660), and risky behavior (Karlsson Linnér et al., 2019, Nature Genetics, 51(2), 245-257). Structural magnetic resonance imaging processing employed FreeSurfer v5.3.0. General linear models were constructed using 32 regions-of-interest identified from suicide neuroimaging literature, with false-discovery-rate correction. SA-in-MDD and SA-in-BD PRSs negatively predicted parahippocampal thickness, with the latter association modified by group membership. SA-in-BD and Risky Behavior PRSs inversely predicted rostral and caudal anterior cingulate structure, respectively, with the latter effect driven by the &quot;high risk&quot; group. SA-in-MDD and SA-in-BD PRSs positively predicted cuneus structure, irrespective of group. This study demonstrated associations between PRSs for suicide-related phenotypes and structural variability in brain regions implicated in SA. Future exploration of extended PRSs, in conjunction with a range of biological, phenotypic, environmental, and experiential data in high risk populations, may inform predictive models for suicidal behaviors.<p /> <p>Language: en</p>",
language="en",
issn="1552-4841",
doi="10.1002/ajmg.b.32879",
url="http://dx.doi.org/10.1002/ajmg.b.32879"
}