Genetics

UBE2E3 locus variants associate with glucocorticoid-induced intraocular pressure rise

In a pharmacogenetic analysis of GC-exposed patients (FAME n=530; replication n=588), rs13425173 in UBE2E3 reached genome-wide significance (P = 2.88e-8). Meta-analysis identified a second UBE2E3 variant, rs1040227, also genome-wide significant in combined cohorts. Colocalization implicates expression regulation of UBE2E3 in multiple tissues, supporting a biologic link to GC-IOP change. WES gene-burden analysis nominated MSTO1 as a rare-variant contributor in the discovery cohort. 1

Disease-risk variants differ from variants modulating early-adversity effects

In ~180,129 UK Biobank participants, GWAS-identified variants for four disorders did not overlap with GWEIS interaction variants, even at p < 5×10⁻⁵. SNP-based heritability was detectable for main genetic effects but absent for interaction effects, especially for mental health outcomes. Findings imply distinct genetic architectures for baseline disease risk versus environment-modulated susceptibility. Relying solely on GWAS signals will miss context-dependent genetic effects relevant to risk prediction. 2

Receiving a precision-medicine treatment recommendation offers hope without more regret

In the PRISM pediatric precision-medicine trial (parents n=303), 68% expected a treatment recommendation at enrollment and 70% of parents actually received one. Parents who received recommendations reported that recommendations provided hope and perceived options. Absence of a recommendation caused disappointment but reassurance that options were explored. Receipt of a recommendation was not associated with increased regret about trial participation (p > 0.05). 3