Biomedical subjects

Allison E Ashley-Koch

Publications and source records attributed to Allison E Ashley-Koch.

3 recordsLinked to original sources

PubMed2026

Suicidality phenotypes reflect both shared and distinct genetic factors.

Suicidality phenotypes, including suicidal ideation (SI), non-fatal suicide attempt (SA), and suicide death (SD), are heritable and exhibit both shared and phenotype-specific genetic influences. Using genomic structural equation modelling, we estimated the shared genetic architecture across GWAS of SI (176,147 cases, 1,010,300 controls), SA (53,919 cases, 1,063,988 controls), and SD (7,584 cases, 652,070 controls) and conducted a multivariate GWAS of a latent suicidality factor capturing their shared liability. This analysis identified 36 genome-wide significant loci, including seven not previously reported in any suicidality GWAS. Follow-up analyses identified residual genetic variance specific to each phenotype, including three SD-specific genomic risk loci. Conditioning suicidality phenotypes on genetic liability to psychiatric disorders revealed significant residual genetic variance across SI, SA, SD, and the suicidality common factor. Together, these results suggest that suicidality reflects both shared genetic liability and phenotype-specific contributions.

Journal Article↗

PubMed2024

Whole-genome sequencing in 333,100 individuals reveals rare non-coding single variant and aggregate associations with height.

The role of rare non-coding variation in complex human phenotypes is still largely unknown. To elucidate the impact of rare variants in regulatory elements, we performed a whole-genome sequencing association analysis for height using 333,100 individuals from three datasets: UK Biobank (N = 200,003), TOPMed (N = 87,652) and All of Us (N = 45,445). We performed rare ( < 0.1% minor-allele-frequency) single-variant and aggregate testing of non-coding variants in regulatory regions based on proximal-regulatory, intergenic-regulatory and deep-intronic annotation. We observed 29 independent variants associated with height at P < after conditioning on previously reported variants, with effect sizes ranging from -7cm to +4.7 cm. We also identified and replicated non-coding aggregate-based associations proximal to HMGA1 containing variants associated with a 5 cm taller height and of highly-conserved variants in MIR497HG on chromosome 17. We have developed an approach for identifying non-coding rare variants in regulatory regions with large effects from whole-genome sequencing data associated with complex traits.

Humans↗

PubMed2020

Epigenome-wide meta-analysis of PTSD across 10 military and civilian cohorts identifies methylation changes in AHRR.

Epigenetic differences may help to distinguish between PTSD cases and trauma-exposed controls. Here, we describe the results of the largest DNA methylation meta-analysis of PTSD to date. Ten cohorts, military and civilian, contribute blood-derived DNA methylation data from 1,896 PTSD cases and trauma-exposed controls. Four CpG sites within the aryl-hydrocarbon receptor repressor (AHRR) associate with PTSD after adjustment for multiple comparisons, with lower DNA methylation in PTSD cases relative to controls. Although AHRR methylation is known to associate with smoking, the AHRR association with PTSD is most pronounced in non-smokers, suggesting the result was independent of smoking status. Evaluation of metabolomics data reveals that AHRR methylation associated with kynurenine levels, which are lower among subjects with PTSD. This study supports epigenetic differences in those with PTSD and suggests a role for decreased kynurenine as a contributor to immune dysregulation in PTSD.

Basic Helix-Loop-Helix Proteins↗