The ankyrin-3 gene is associated with posttraumatic stress disorder and externalizing comorbidity.
- Authors
- Logue, Mark W; Solovieff, Nadia; Leussis, Melanie P; Wolf, Erika J; Melista, Efthymia; Baldwin, Clinton; Koenen, Karestan C; Petryshen, Tracey L; Miller, Mark W
- Year
- 2013
- Journal
- Psychoneuroendocrinology
- PMID
- 23796624
- DOI
- 10.1016/j.psyneuen.2013.04.013
- PMCID
- PMC3775967
BACKGROUND: The ankyrin 3 gene (ANK3) produces the ankyrin G protein that plays an integral role in regulating neuronal activity. Previous studies have linked ANK3 to bipolar disorder and schizophrenia. A recent mouse study suggests that ANK3 may regulate behavioral disinhibition and stress reactivity. This led us to hypothesize that ANK3 might also be associated with stress-related psychopathology such as posttraumatic stress disorder (PTSD), as well as disorders of the externalizing spectrum such as antisocial personality disorder and substance-related disorders that are etiologically linked to impulsivity and temperamental disinhibition. METHODS: We examined the possibility of association between ANK3 SNPs and both PTSD and externalizing (defined by a factor score representing a composite of adult antisociality and substance abuse) in a cohort of white non-Hispanic combat veterans and their intimate partners (n=554). Initially, we focused on rs9804190-a SNP previously reported to be associated with bipolar disorder, schizophrenia, and ankyrin G expression in brain. Then we examined 358 additional ANK3 SNPs utilizing a multiple-testing correction. RESULTS: rs9804190 was associated with both externalizing and PTSD (p=0.028 and p=0.042 respectively). Analysis of other ANK3 SNPs identified several that were more strongly associated with either trait. The most significant association with externalizing was observed at rs1049862 (p=0.00040, pcorrected=0.60). The most significant association with PTSD (p=0.00060, pcorrected=0.045) was found with three SNPs in complete linkage disequilibrium (LD)-rs28932171, rs11599164, and rs17208576. CONCLUSIONS: These findings support a role of ANK3 in risk of stress-related and externalizing disorders, beyond its previous associations with bipolar disorder and schizophrenia.
Association results for the externalizing factor score (EFS; blue circles) and for posttraumatic stress disorder (PTSD; green circles), and corresponding positions of the brain-specific (NM_020987.3) and other ANK3 isoforms. The 3′ SNP rs9804190 was tested in the first stage based on prior evidence for association with both bipolar disorder and ankyrin G expression in brain. SNPs spanning the ANK3 locus encompassing all isoforms were tested in the second stage.
Linkage Disequilibrium in the associated region of ANK3 (from 61,789,272 to 61,869,059). Plots contain either (A) all SNPs or (B) only PTSD and externalizing-associated SNPs presented in table 1. Blue line/arrows indicate externalizing-associated SNPs (Table 1 SNPs 1 to 4). Green line/arrows indicate PTSD-associated SNPs including rs9804190 (Table 1 SNPs 5 to 12).
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| Expression of ANK3 moderates the association between childhood trauma and affective traits in severe mental disorders. | Aas M et al. | — | 2023 | → |
| Conceptualizing traumatic stress and the structure of posttraumatic psychopathology through the lenses of RDoC and HiTOP. | Hawn SE et al. | — | 2022 | → |
| Ankyrins and neurological disease. | Stevens SR et al. | — | 2021 | → |
| Internalizing and externalizing psychopathology in middle age: genetic and environmental architecture and stability of symptoms over 15 to 20 years. | Gustavson DE et al. | — | 2020 | → |
| Overrepresentation of genetic variation in the AnkyrinG interactome is related to a range of neurodevelopmental disorders. | van der Werf IM et al. | — | 2020 | → |
| Unravelling the genetic basis of schizophrenia and bipolar disorder with GWAS: A systematic review. | Prata DP et al. | — | 2019 | → |
| Anxiety Associated Increased CpG Methylation in the Promoter of Asb1: A Translational Approach Evidenced by Epidemiological and Clinical Studies and a Murine Model. | Emeny RT et al. | — | 2018 | → |
| Post-Traumatic Stress Disorder Delineating the Progression and Underlying Mechanisms Following Blast Traumatic Brain Injury. | Lucke-Wold B et al. | — | 2018 | → |
| Association analysis of ANK3 variants with bipolar disorder in the Korean population. | Cho CH et al. | — | 2017 | → |
| Effects of ANK3 variation on gray and white matter in bipolar disorder. | Lippard ETC et al. | — | 2017 | → |
| NF-κB regulates neuronal ankyrin-G via a negative feedback loop. | König HG et al. | — | 2017 | → |
| Pharmacogenetics and Pharmacotherapy of Military Personnel Suffering from Post-traumatic Stress Disorder. | Naß J et al. | — | 2017 | → |
| Aggressive behavior in humans: Genes and pathways identified through association studies. | Fernàndez-Castillo N et al. | — | 2016 | → |
| Ankyrin-3 as a molecular marker of early-life stress and vulnerability to psychiatric disorders. | Luoni A et al. | — | 2016 | → |
| Genetics of aggressive behavior: An overview. | Veroude K et al. | — | 2016 | → |
| Mood, stress and longevity: convergence on ANK3. | Rangaraju S et al. | — | 2016 | → |
| Polygenic Risk for Externalizing Psychopathology and Executive Dysfunction in Trauma-Exposed Veterans. | Sadeh N et al. | — | 2016 | → |
| An α-synuclein gene (SNCA) polymorphism moderates the association of PTSD symptomatology with hazardous alcohol use, but not with aggression-related measures. | Guillot CR et al. | — | 2015 | → |
| Genome-wide association study of posttraumatic stress disorder in a cohort of Iraq-Afghanistan era veterans. | Ashley-Koch AE et al. | — | 2015 | → |
| Genomic predictors of combat stress vulnerability and resilience in U.S. Marines: A genome-wide association study across multiple ancestries implicates PRTFDC1 as a potential PTSD gene. | Nievergelt CM et al. | — | 2015 | → |
| New perspectives in human tear analysis? | Kukumberg P et al. | — | 2015 | → |
| Cognitive effects of the ANK3 risk variants in patients with bipolar disorder and healthy individuals. | Hori H et al. | — | 2014 | → |
| Ethanol treatment of lymphoblastoid cell lines from alcoholics and non-alcoholics causes many subtle changes in gene expression. | McClintick JN et al. | — | 2014 | → |
| Interaction of the ADRB2 gene polymorphism with childhood trauma in predicting adult symptoms of posttraumatic stress disorder. | Liberzon I et al. | — | 2014 | → |
| Progress towards understanding the genetics of posttraumatic stress disorder. | Voisey J et al. | — | 2014 | → |
| Role of the axonal initial segment in psychiatric disorders: function, dysfunction, and intervention. | Hsu WC et al. | — | 2014 | → |