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Heritable Risk and Protective Genetic Components of Glaucoma Medication Non-Adherence.

Julie L Barr1,2, Michael Feehan2,3, Casey Tak4

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Glaucoma medication non-adherence has a significant genetic component, with 47-58% heritability. Specific gene mutations and pathways were identified, suggesting novel therapeutic targets for improving patient adherence.

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Area of Science:

  • Genetics
  • Ophthalmology
  • Pharmacogenomics

Background:

  • Glaucoma is a leading cause of irreversible blindness, impacting millions worldwide.
  • Medication non-adherence is a significant challenge in glaucoma management, despite interventions.
  • The underlying causes of persistent non-adherence are not fully understood.

Purpose of the Study:

  • To investigate the heritability of glaucoma medication non-adherence.
  • To identify specific genetic variants and pathways associated with non-adherence.
  • To explore potential genetic targets for improving medication adherence in glaucoma patients.

Main Methods:

  • Assessed medication non-adherence using prescription refill data (MPR, PDC) over 12 months.
  • Conducted genotyping (Illumina HumanCoreExome BeadChip) and whole exome sequencing on 230 patients.
  • Utilized Genome-wide complex trait analysis (GCTA) and Ingenuity Pathway Analysis (IPA).

Main Results:

  • 59-67% of patients exhibited medication non-adherence (MPR80, PDC80).
  • Heritability estimates for non-adherence ranged from 48% to 57%.
  • Identified significant missense mutations in genes including CHCHD6, TTC28, and TINAG, with CHCHD6 showing a three-fold increased risk.

Conclusions:

  • A substantial genetic component underlies glaucoma medication non-adherence.
  • Specific genes and pathways (e.g., CHCHD6, opioid signaling, drug metabolism) are associated with adherence.
  • Findings suggest potential for genetically informed strategies to improve glaucoma treatment adherence.