OBJECTIVE: Genome-wide association studies (GWAS) implicate psychiatric, metabolic, and anthropometric factors in anorexia nervosa. We developed an 'experiential genetics' design, layering qualitative methodology atop GWAS to capture the subjective experience of anorexia nervosa. METHOD: We randomly selected GWAS participants with anorexia nervosa from the highest (n = 10) and lowest (n = 10) anorexia nervosa polygenic risk scores (PRS). Clinicians blind to PRS group conducted semi-structured interviews exploring the perception of symptoms, onset, course, and physical and psychological experience of negative energy balance (NEB) (i.e. the pathognomonic anorexia nervosa symptom of expending more energy than one consumes). Blind raters rated transcripts
experiential themes and subthemes were identified through thematic analysis. RESULTS: Themes indicated that the high-PRS group reported more lifetime psychiatric problems, described the descent into anorexia nervosa as a purposeful progression of preexisting preoccupations, experienced NEB as more positive and energizing, and were more often symptomatic at interview
for them anorexia nervosa seemed to represent the apex of a life trajectory centered on eating disorder traits and symptoms. The low-PRS group reported fewer lifetime psychiatric problems, a more environmentally determined illness onset, fewer extreme symptoms, and were less symptomatic at interview
for them anorexia nervosa seemed to constitute a transient interruption of their life trajectory. Interviewers correctly guessed group membership less frequently than chance (43%), questioning whether the dimensions commonly associated with anorexia nervosa capture the genetic essence of anorexia nervosa. CONCLUSION: Qualitative research can capture the phenotypic expression of genetic risk, enrich GWAS, characterize heterogeneity, and inform development of genetically informed interventions.