👤 Jeanelle Sheeder

To identify novel genetic loci associated with differences in serum etonogestrel concentrations among contraceptive implant users. We conducted a cross-sectional analysis in which we enrolled healthy, reproductive-aged (age 18-45 years) participants who had been using etonogestrel implants for 12-48 months. Participants underwent a single-time blood draw for measurement of serum etonogestrel concentrations by liquid chromatography-tandem mass spectrometry and the extraction of DNA from whole blood. We genotyped participants using the Illumina Infinium Global Diversity Array with Enhanced PGx and imputed genotyping results using the TOPMed imputation server. We performed genome-wide complex trait analysis using a linear mixed model leave-one-chromosome-out association analysis to identify genetic variants associated with serum etonogestrel concentrations. We enrolled 900 etonogestrel implant users, with a median age of 22.3 years (range 18.0-41.5 years), median body mass index (BMI) 26.0 (range 18.5-52.0), and median duration of implant use 27 months (range 12-48 months). Most participants self-reported their race as White (49.3%) and ethnicity as Hispanic or Latina (52.9%). Participants had a median serum etonogestrel concentration of 126.9 pg/mL (range 39.4-695.1 pg/mL). Including BMI, duration of implant use, and three principal components as covariates in the genome-wide complex trait analysis, we identified no genetic variants with minor allele frequencies at or above 5% that were associated with serum etonogestrel concentrations at genome-wide significance ( Despite enhanced coverage for known pharmacogenomic variants, we found no significant associations between interindividual variability in contraceptive implant pharmacokinetics and genetic loci directly involved in exogenous steroid hormone metabolism. ClinicalTrials.gov, NCT03092037. Show less