HomeClinical White PapersGet to know a gene: ANK3 Get to know a gene: ANK3 July 14, 2017Clinical White Papers Summary: ANK3 has not been shown to inform on patient medication response and therefore is not a pharmacogenomic marker. As a disease marker, it lacks clinical utility. There is an association between ANK3 and bipolar disorder, but the contribution of ANK3 to disease risk is very small. Therefore, genetic testing for ANK3 is not recommended at this time. What is ANK3? ANK3 encodes Ankyrin-G, a protein that is important for the function of sodium ion channels and modulation of neuronal excitability. While ANK3 has been studied as a potential disease marker for bipolar disorder and schizophrenia, there are currently no studies investigating the effect of ANK3 variants on response to psychiatric medications. Is ANK3 a risk factor for bipolar disorder and schizophrenia disease states? Single nucleotide polymorphisms (SNPs) within ANK3 have consistently reached genome-wide significance (p<5 x 10-8) for an association with bipolar disorder.1–3 However, the effect size is small (OR=1.27-1.45), and ANK3 is only one of many susceptibility genes that impact the risk for bipolar disorder. Some of the many other genes associated with bipolar disorder include CACNA1C, TRANK1, and MHC.2,4 SNPs within ANK3 failed to reach genome-wide significance for an association with schizophrenia.5–7 What is the clinical significance of ANK3 genotyping? Although ANK3 may be involved in the biology of disease, it is not useful for predicting how a patient will respond to medications. There are currently no studies investigating the effect of ANK3 variants on psychiatric treatment response. Therefore, ANK3 is not a pharmacogenomic marker and is not currently included on the GeneSight® test panels. While a positive association has been shown between ANK3 and bipolar disorder1–3, an association between ANK3 and schizophrenia has not been supported5–7. It has been hypothesized that a potential reason ANK3 may play a role in bipolar disorder is that variation in ANK3 may result in dysregulation of sodium ion channels, which may increase excitatory signaling in the brain and affect mood regulation. However, while ANK3 is valid as a marker for bipolar disorder, the actual contribution of ANK3 to disease risk is very small, and ANK3 is only one of many susceptibility genes. Without a proper understanding of the modest clinical impact of ANK3 variation, testing for ANK3 may lead to overestimation of disease risk, unnecessary use of antipsychotic and mood stabilizing medications, and undue patient anxiety regarding the development of serious conditions. Therefore, genetic testing for ANK3 is not recommended at this time. References 1. Ferreira, M., O’Donovan, M. & Meng, Y. Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder. Nat. … 40, 1056–1058 (2008). 2. Chen, D. T. et al. Genome-wide association study meta-analysis of European and Asian-ancestry samples identifies three novel loci associated with bipolar disorder. Mol. Psychiatry 18, 195–205 (2013). 3. Mühleisen, T. W. et al. Genome-wide association study reveals two new risk loci for bipolar disorder. Nat. Commun. 5, 3339 (2014). 4. Ruderfer, D. M. et al. Polygenic dissection of diagnosis and clinical dimensions of bipolar disorder and schizophrenia. Mol Psychiatry 19, 1017–1024 (2014). 5. Athanasiu, L., Mattingsdal, M. & Kähler, A. Gene variants associated with schizophrenia in a Norwegian genome-wide study are replicated in a large European cohort. J. Psychiatr. … 44, 748–753 (2010). 6. Ripke, S., Sanders, A. & Kendler, K. Genome-wide association study identifies five new schizophrenia loci. Nat. … 43, 969–976 (2011). 7. Bergen, S. E. et al. Genome-wide association in a Swedish population yields support for greater CNV and MHC involvement in schizophrenia compared with bipolar disorder. Mol Psychiatry 17, 880–886 (2012 Patient MTHFR Mutations: Clinical Implications and Management Strategies MTHFR mutations—changes in the methylenetetrahydrofolate reductase (MTHFR) gene—have gained increased attention in the medical community due to their potent... Read more Patient Can an App Help Me Manage My Anxiety? Health and wellness smartphone apps have become so common that if you can name a health goal, desire or condition, you can probably find an app for it. N... Read more Patient Black Trailblazers of Psychiatry and Mental Health: A Legacy of Healing and Advocacy As we celebrate Black History Month, we want to recognize a few individuals who have made extraordinary contributions to the field of psychiatry and mental heal... 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Patient MTHFR Mutations: Clinical Implications and Management Strategies MTHFR mutations—changes in the methylenetetrahydrofolate reductase (MTHFR) gene—have gained increased attention in the medical community due to their potent... Read more
Patient Can an App Help Me Manage My Anxiety? Health and wellness smartphone apps have become so common that if you can name a health goal, desire or condition, you can probably find an app for it. N... Read more
Patient Black Trailblazers of Psychiatry and Mental Health: A Legacy of Healing and Advocacy As we celebrate Black History Month, we want to recognize a few individuals who have made extraordinary contributions to the field of psychiatry and mental heal... Read more
Patient Mindful Moments: Tips for Anxiety If a well-meaning friend or family member has ever told you to “just breathe” when you’re feeling worked up or stressed out, you’d be forgiven if you felt l... Read more
Patient Hints To Help You Have A Better New Year The holidays have ended, and a new year has begun—a time when many embrace a fresh start by setting New Year’s resolutions. This year, why not consider s... Read more
Patient Movement as Medicine: Solutions for Anxiety Moving forward. It sounds like a nice idea, especially when you’re feeling stuck deep in the throes of an anxiety spiral. But it turns out that physically m... Read more
Patient Weight-Loss Drugs and Mental Health: What You Need to Know New medications for weight loss seem to be flying off pharmacy shelves these days. But could they be linked to mental health conditions? Researchers are ... Read more
Patient 3 million patients (and counting!) have now taken the GeneSight test! We’re thrilled to share that 3 million patients (and counting!) have now taken the GeneSight test! We're so grateful to the dedicated healthcare providers who... Read more
Patient The Model Minority Myth and Mental Health The model minority myth stereotypes one cultural group, typically Asian Americans, as “intelligent, hard-working, and diligent and therefore more academically, ... Read more
Healthcare Provider How Clinicians Can Help Support Their Patients Who Are Being Bullied How Clinicians Can Help Support Their Patients Who Are Being Bullied Acts of bullying can cause feelings of fear, loneliness and sadness, as well as depressi... Read more