About

Allison Elizabeth Ashley-Koch is a Professor in Medicine, Molecular Genetics and Microbiology, and Biostatistics and Bioinformatics at Duke University. She is a faculty member of the Duke Institute for Brain Sciences and the Duke Molecular Physiology Institute. Her research focuses on biostatistics, bioinformatics, and genetics, contributing to the understanding of complex biological systems and diseases. She is associated with the Duke Center for Statistical Genetics and Genomics, engaging in research that advances the fields of genomics and biomedical informatics.

Selected publications

• DNA methylation signatures associated with bipolar disorder in peripheral blood improve prediction models

  EBioMedicine · 2026-05-12

  articleOpen access

  BACKGROUND: Bipolar disorder (BD) is a major mood disorder influenced by both genetic and environmental factors. While DNA methylation from peripheral tissues can reflect both genetic and environmental influences and reveal insights into disease biology, it remains understudied in BD. DNA methylation signatures may complement polygenic scores (PGS) and hold potential as biomarkers. Here, we conducted the largest epigenome-wide association study (EWAS) of BD to date and evaluated the predictive value of polymethylation scores (PMS) in classifying case-control status. METHODS: DNA methylation from peripheral blood of 1729 cases and 1747 controls, comprising twelve cohorts, was obtained. We performed meta-analyses for the total sample, male-only, and female-only analyses. Differentially methylated regions (DMRs) were identified using the comb-p method. Polymethylation scores for BD (BD-PMS) were tested for association with BD, and in combination with PGS. FINDINGS: We identified 47 differentially methylated CpG positions (DMPs) in the total and four in the female-only analysis. Ninety, fourteen and six DMRs were identified in the total sample, female-only, and male-only analyses, respectively. Genes annotated to the top DMPs were enriched for immune activation and phosphorylation pathways. DMRs were annotated to genes relevant to neurotransmission, including GABBR1 and CACNA2D4. BD-PMS explained 2% of the variance in BD case-control status, and improved the variance explained from 7.9 to 8.5% when combined with PGS. For bipolar I disorder, BD-PMS explained 4.9% of the variance, and improved the variance explained by PGS from 15.9 to 18.5%. Association of BD with PMS for schizophrenia and major depression suggests pleiotropic epigenetic effects. INTERPRETATION: DNA methylation signatures of BD are detectable in blood using adequately powered data and may reveal novel BD biology that is not captured by genetic studies. PMS from large cohorts have the potential to facilitate the development of prediction tools to aid clinical decision-making. FUNDING: This investigation was primarily funded by the Research Council of Norway (RCN #250299, #273446, #223273) and the University of Bergen. A complete list of funding organisations is provided in the Acknowledgements.

  PublisherDOI

• Examining the timing of trauma, PTSD onset, and DNA methylation: A multicohort investigation of candidate CpG sites

  Journal of Psychiatric Research · 2025-07-31

  articleOpen access
  PublisherOA PDFDOI

• Genomic Analysis of Trichotillomania

  American Journal of Medical Genetics Part B Neuropsychiatric Genetics · 2025-06-13 · 1 citations

  articleOpen access

  ABSTRACT Trichotillomania (TTM) is a psychiatric condition in which people feel an overwhelming urge to pull out their hair, resulting in noticeable hair loss and significant distress. Twin and family studies suggest that TTM is at least partly genetic, but no genome‐wide analyses have been completed. To fill the gap in this field, we have conducted a case–control study of genotype array data from 101 European ancestry TTM cases and 488 ancestry‐matched unaffected controls. TTM cases were ascertained in the United States through web‐based recruitment, patient support groups, and conferences organized by the Trichotillomania Learning Center. Following clinical confirmation of a TTM diagnosis, patients completed self‐report assessments of frequency and duration of hair pulling, other psychiatric symptoms, and family history. Unaffected controls were also ascertained in the United States and were matched to cases by ancestry. In the first formal genome‐wide association study of TTM, we did not identify any common variants with a genome‐wide significant ( p < 5 × 10 −8 ) association level with case status. We found that cases carry a higher load of common polygenic risk for psychiatric disorders ( p = 0.008). We also detected copy number variants previously associated with neuropsychiatric disorders (specifically, deletions in NRXN1 , CSMD1, and 15q11.2). These results further support genetics' role in the etiology of TTM and suggest that larger studies are likely to identify risk variation and, ultimately, specific risk genes associated with the condition.

  PublisherOA PDFDOI

• Unraveling the genetic complexity of Alzheimer's disease across diverse populations via integrative single‐cell multi‐omics

  Alzheimer s & Dementia · 2025-12-01

  articleOpen access

  BACKGROUND: The multifactorial and heterogenous nature of Late Onset Alzheimer's disease (LOAD) presents a challenge, particularly in capturing genetic complexity across diverse populations. Recent single-nucleus (sn)multi-omics analyses have advanced the LOAD genetics field. However, most studies were conducted in European ancestry subjects, while other populations remain largely understudied. Here, we aimed to explore the underpinning genetics of LOAD in diverse populations and to gain insights into the shared (pan-ethnic) and distinct (ancestry-specific) genetic drivers of LOAD between European and African ancestries. METHODS: We analyzed cortical tissues from European (EA) and African ancestry (AA) LOAD and control donors, and simultaneously characterized their transcriptomic (snRNA-seq) and chromatin accessibility (snATAC-seq) profiles at a single-cell level using 10x Genomics Multiome technology. We analyzed these datasets using our integrative genomic pipeline to catalogue differentially expressed genes (DEGs) in LOAD and to identify candidate cis-regulatory elements (cCREs) and their target DEGs at the cell-subtype level. Finally, we performed differential-expression analysis on the combined snRNA-seq datasets from both ancestries and modeled ancestry interactions for statistically robust inference of shared and divergent DEGs between ancestries. RESULTS: EA and AA nuclei were clustered into 32 cell-subtypes each, representing 8 major neuronal and glial cell types. The highest numbers of DEGs were found in GABAergic and interneuron subtypes in EA vs. GABAergic neuron and oligodendrocyte subtypes in AA. Analysis of cCRE-DEG pairs revealed differential chromatin interactions governing gene dysregulation across ancestries. For example, microglial APOE expression was predicted be regulated by six EA-specific and four AA-specific cCREs, and only one common cCRE. Differential expression analysis revealed the highest numbers of pan-ethnic DEGs in specific excitatory and inhibitory neuronal subtypes, with excitatory-neuron DEGs primarily associated with cellular growth and extracellular matrix assembly, and inhibitory-neuron DEGs largely associated with membrane trafficking. Ancestry-specific DEGs were more commonly identified in AA compared to EA. AA-specific DEGs were also primarily in excitatory-neurons, with roles in fatty acid metabolism and neuronal structure, and in inhibitory-neurons with roles in respiration and synaptic transmission. CONCLUSIONS: These results enhance our understanding of the shared and distinct cell-subtype gene dysregulation networks and biological processes underlying LOAD in African vs. European ancestries.

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• PTSD and suPAR: A multicohort investigation of chronic inflammation

  Brain Behavior and Immunity · 2025-10-28 · 2 citations

  articleOpen access
  PublisherOA PDFDOI

• A genome‐wide association study of alloimmunization in the TOPMed OMG‐SCD cohort identifies a locus on chromosome 12

  UNC Libraries · 2025-10-22

  articleOpen access

  BACKGROUND: Red cell alloimmunization after exposure to donor red cells is a very common complication of transfusion for patients with sickle cell disease (SCD), resulting frequently in accelerated donor red blood cell destruction. Patients show substantial differences in their predisposition to alloimmunization, and genetic variability is one proposed component. Although several genetic association studies have been conducted for alloimmunization, the results have been inconsistent, and the genetic determinants of alloimmunization remain largely unknown. STUDY DESIGN AND METHODS: We performed a genome-wide association study (GWAS) in 236 African American (AA) SCD patients from the Outcome Modifying Genes in Sickle Cell Disease (OMG-SCD) cohort, which is part of Trans-Omics for Precision Medicine (TOPMed), with whole-genome sequencing data available. We also performed sensitivity analyses adjusting for different sets of covariates and applied different sample grouping strategies based on the number of alloantibodies patients developed. RESULTS: We identified one genome-wide significant locus on chr12 (p = 3.1e-9) with no evidence of genomic inflation (lambda = 1.003). Further leveraging QTL evidence from GTEx whole blood and/or Jackson Heart Study PBMC RNA-Seq data, we identified a number of potential genes, such as ARHGAP9, STAT6, and ATP23, that may be driving the association signal. We also discovered some suggestive loci using different analysis strategies. DISCUSSION: We call for the community to collect additional alloantibody information within SCD cohorts to further the understanding of the genetic basis of alloimmunization in order to improve transfusion outcomes.

  PublisherDOI

• A statistical framework for multi-trait rare variant analysis in large-scale whole-genome sequencing studies

  Nature Computational Science · 2025-02-07 · 9 citations

  articleOpen access
  PublisherOA PDFDOI

• Whole exome sequencing analysis of suicidal thoughts and behaviors in a veteran cohort implicates inflammatory pathways and genes previously associated with psychiatric and neurodegenerative diseases

  Journal of Affective Disorders · 2025-09-11 · 1 citations

  articleSenior author
  PublisherDOI

• Trauma, posttraumatic stress disorder, and incident chronic disease.

  PubMed · 2025-01-04

  articleOpen access

  BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with chronic disease risk, particularly cardiovascular disease (CVD). However, few studies have combined detailed measurements of trauma exposure and PTSD with incident chronic disease outcomes assessed using electronic health records (EHRs). PURPOSE: Our study examined associations between traumatic stress (combat exposure, lifetime trauma exposure, PTSD symptoms, and PTSD diagnosis) and chronic disease outcomes, including 7 clinical risk factors and 11 major chronic disease diagnoses assessed using EHRs. METHODS: Participants included 3696 post-9/11 US veterans enrolled in the VISN 6 (Veterans Integrated Service Networks 6) MIRECC (Mental Illness Research, Education, and Clinical Center)'s Post-Deployment Mental Health Study cohort who averaged 38.1 years old at baseline with 13.3 years of follow-up. RESULTS: At baseline, greater PTSD symptoms were associated with higher body mass, more alcohol use, higher rates of smoking, hypertension, and hyperlipidemia. Over follow-up, veterans with more combat exposure (HR, 1.11; 95% CI, 1.04-1.19; P = .002), trauma exposure (HR, 1.15; 95% CI, 1.08-1.23; P < .001), PTSD symptoms (HR, 1.22; 95% CI, 1.14-1.30; P < .001), or a diagnosis of PTSD (HR, 1.39; 95% CI, 1.21-1.59; P < .001) developed more chronic disease. PTSD symptoms and diagnostic status showed consistent associations with incident onset of CVD, diabetes, and pulmonary disease, and associations remained when accounting for non-PTSD psychiatric diagnoses. Compared to veterans with current PTSD, veterans with past PTSD had reduced risk of developing chronic diseases. CONCLUSIONS: Future research should examine if treating PTSD and the sequelae of trauma has the potential to reduce risk for chronic disease, particularly CVD, diabetes, and pulmonary disease.

  PublisherOA PDFDOI

• A Human Glomerular Disease Atlas defines the APOL1-JAK-STAT feed forward loop in focal segmental glomerulosclerosis

  medRxiv · 2025-09-14 · 2 citations

  preprintOpen access

  Abstract There are few approved treatments for glomerular diseases of the kidney. To map underlying transcriptional programs in the kidney driving rare glomerular diseases, single-nucleus RNA sequencing (snRNAseq) on kidney biopsies (N=120) from the Nephrotic Syndrome Study Network were integrated with snRNAseq and single-cell sequencing (scRNAseq) of reference kidney tissue (N=50) to create the Omnibus of CElls And Nuclei (OCEAN). Unsupervised analysis of multi-cellular programs identified that JAK-STAT pathway activity was associated with clinical measures of disease severity. JAK-STAT pathway activity was strongly correlated with apolipoprotein1 (APOL1) mRNA transcript expression and the high risk APOL1 variant genotype, a major risk factor for focal segmental glomerulosclerosis. These findings were confirmed in an independent study of Black participants where loss of APOL1 function decreased JAK-STAT pathway activation in ex vivo models of patient-derived podocytes. The findings presented are consistent with a feed forward loop regulating the JAK-STAT-APOL1 driven tissue damage, providing mechanistic support for the JUSTICE Phase II trial targeting JAK activation in APOL1-mediated kidney disease.

  PublisherOA PDFDOI