Arlene S Chung, Katherine L Pattee, Rachel Bass, Adam N Frisch, Jaime Jordan
Program director longevity in emergency medicine residencies: A 40-year analysis
AEM education and training
based emerging evidence role specific singlenucleotide variants snvs eif2ak3 encoding integrated stress response kinase perk neurodegeneration assessed association eif2ak3 snvs neurocognitive performance people hiv pwh using candidate gene approach retrospective study included charter cohort participants excluding severe neuropsychiatric comorbidities genomewide data previously obtained 1047 participants targeted sequencing 992 participants available genomic dna utilized interrogate association three noncoding three coding eif2ak3 snvs continuous global deficit score gds global neurocognitive impairment nci gds 05 using univariable multivariable methods demographic diseaseassociated treatment characteristics covariates cohort characteristics follows median age 431 years females 228 european ancestry 41 median cd4 cell counts 175l nadir 428l current first assessment 705 used art 683 plasma hiv rna levels 200 copiesml three noncoding eif2ak3 snvs associated gds nci p 005 additionally 309 309 412 participants least one risk allele coding snvs rs1805165 g rs867529 g rs13045 respectively homozygosity three coding snvs associated significantly worse gds p 0001 nci p 0001 multivariable analysis rs13045 risk allele current art use beck depression inventoryii value 13 independently associated gds nci p 0001 whereas two coding snvs significantly correlate gds nci including rs13045 model coding eif2ak3 snvs associated worse performance executive functioning motor functioning learning verbal fluency coding noncoding snvs eif2ak3 associated global nc domainspecific performance effects smalltomedium size present multivariable analyses raising possibility specific snvs eif2ak3 important component genetic vulnerability neurocognitive complications pwh