My research vision is two-fold. First, in the mental health and psychopathology research space, I aim to improve the lives of affected individuals by studying risk stratification, related health outcomes, and pharmacological and non-pharmacological (i.e., environmental and behavioral change) intervention strategies. Second, in a community equity and forensic science research space, I aim to develop and deploy genetic strategies to model ancestry diversity in the context of biological evidence in legal proceedings. ​
In the mental health space, my scientific inquiry focuses on posttraumatic stress disorder (PTSD), major depression, anxiety, and the thoughts/behaviors associated with death by suicide. Because I study trait relationships, these often serve as the anchor to which other correlated mental health and/or peripheral health phenotypes can be studied. I have interests in the following areas related to these traits that, for brevity, I loosely refer to as internalizing psychopathologies
  • Tandem repeats (TRs) associated with health and disease
    • Wendt FR, Pathak GA, Polimanti R. Phenome-wide association study of loci harboring de novo tandem repeat mutations in UK Biobank exomes. medRxiv doi: https://doi.org/10.1101/2022.01.26.22269821
  • Leveraging trait relationships to better understand genetic liability to internalizing symptoms
    • Wendt FR, et al. Multivariate genome-wide analysis of education, socioeconomic status and brain phenome. Nature Human Behavior. PMID: 33349686.
    • Tamman AJF, Wendt FR, et al.  Attachment Style Moderates Polygenic Risk for Posttraumatic Stress in United States Military Veterans: Results From the National Health and Resilience in Veterans Study. Biological Psychiatry. PMID: 33276944.
    • Bountress KE* & Wendt FR*, et al. (shared first authorship). Potential causal effect of posttraumatic stress disorder (PTSD) on alcohol use disorder and alcohol consumption in individuals of European descent: A Mendelian Randomization Study. Alcohol Clinical and Experimental Research. PMID: 34120358.
    • Stein MB, Levey DF, Cheng Z, Wendt FR, et al. Genome-wide association analyses of post-traumatic stress disorder and its symptom subdomains in the Million Veteran Program. Nature Genetics. PMID 33510476.
    • Levey DF, Stein MB, Wendt FR, et al. Bi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions. Nature Neuroscience. PMID 34045744.
    • Wendt FR, et al. Using phenotype risk scores to enhance gene discovery for generalized anxiety disorder and posttraumatic stress disorder. Molecular Psychiatry. PMID: 35181757.
  • Environmental stressors moderating genetic risk factors for internalizing psychopathologies
    • Polimanti R, Levey DF, Pathak GA, Wendt FR, et al. Multi-environment gene interactions linked to the interplay between polysubstance dependence and suicidality. Translational Psychiatry. PMID: 33431810.
    • Wendt FR, et al. Sex-stratified gene-by-environment genome-wide interaction study of trauma, posttraumatic-stress, and suicidality. Neurobiology of Stress. PMID: 33665242.
    • Na PJ, De Angelis F, Nichter B, Wendt FR, et al. Suicidal thinking in context: Moderators of polygenic risk for suicidal ideation in U.S. military veterans: A 7-year, prospective cohort study. Molecular Psychiatry. PMID: 34725455.
    • Wendt FR, et al. Higher polygenic scores for empathy increase posttraumatic stress severity in response to certain traumatic events. In Press Neurobiology of Stress.
In the applied genomics/forensic science space, I am interested in developing ways to reduce bias in DNA “match statistics” (i.e., the probability that person X is the origin of the biological material found on item Y) and other forensic identification statistics. I have specific interest in the following areas:
  • Polygenic prediction of outwardly visible characteristics
    • This is an active area of investigation. Stay tuned for pre-prints coming Spring/Summer 2022!
  • The influence of ancestry diversity on DNA match statistic reliability and equity
    • Novroski NMM, Moo-Choy A, Wendt FR. Allele frequencies and minor contributor match statistic convergence using simulated population replicates. Revise and resubmit.
    • Balasuriya A, Novroski NMM, Wendt FR. Predicting STR genotypes from identity-informative SNPs across three ancestry groups. (manuscript in preparation)
  • Pharmacogenomics for personalized medicine and postmortem investigation
    • Hung AM, Shah SC, Bick AG, Yu Z, Chen HC, Hunt CM, Wendt FR, ..., Siew ED; VA Million Veteran Program COVID-19 Science Initiative. APOL1 Risk Variants, Acute Kidney Injury, and Death in Participants With African Ancestry Hospitalized With COVID-19 From the Million Veteran Program. JAMA Internal Medicine. PMID: 35089317.
    • Hatoum AS, Wendt FR, et al. Ancestry may confound genetic machine learning: Candidate-gene prediction of opioid use disorder as an example. Drug and Alcohol Dependence. PMID: 34710714.
    • Wendt FR, et al. Global genetic variation of select opiate metabolism genes in self-reported healthy individuals. The Pharmacogenomics Journal. PMID: 28398354.
    • Wendt FR, et al. Supervised Classification of CYP2D6 Genotype and Metabolizer Phenotype With Postmortem Tramadol-Exposed Finns. Am J Forensic Med Pathol. PubMed PMID: 30507617.
    • Wendt FR, et al. A pathway-driven predictive model of tramadol pharmacogenetics.Eur J Hum Genet. PMID: 30824817
    • Wendt FR, et al. A genome-wide association study of tramadol metabolism from post-mortem samples. Pharmacogenomics J. PMID: 30971809.
    • Johnson EC, Demontis D, Thorgeirsson TE, Walters RK, Polimanti R, Hatoum AS, Sanchez-Roige S, Paul SE, Wendt FR, ... A large-scale genome-wide association study meta-analysis of cannabis use disorder. Lancet Psychiatry. PMID: 33096046.
    • Wendt FR, Koller D, Pathak GA, Jacoby D, Miller EJ, Polimanti R. Biobank scale pharmacogenomics informs the genetic underpinnings of simvastatin use. Clin Pharmacol Ther. PMID: 33837531.
Across these scientific domains, I have developed an appreciation for the consequence of, and necessity for, inclusive population assignments in genomics research. To this goal, I collaborate with, and receive financial support/sponsorship from, humanities and science departments such as the Yale Center for the Study of Race, Indigeneity, and Transnational Migration. My long-term interests in this space are:
  • Gene discovery in US Military Veterans using ethnicity and genetically predicted classifiers
    • Wendt FR, ..., VA Million Veteran Program, Gaziano JM, Gelernter J, Aslan M, Provenzale D, Helmer D, Hauser E, Polimanti R, on behalf of Department of Veteran Affairs Cooperative Study Program (#2006). Modeling the longitudinal changes of ancestry diversity in the Million Veteran Program. bioRxiv doi: https://doi.org/10.1101/2022.01.24.477583.
  • Multi-ancestry investigation of the genetic liability to suicide and suicidality​​
    • This is an active area of investigation. Stay tuned for pre-prints coming Summer 2022!
  • Psychopathology-wide multi-ancestry effects of the contactin gene family​
    • This is an active area of investigation. Stay tuned for pre-prints coming Summer 2022!