Lindstedt Katarina, Monell Elin, Birgegård Andreas, Bulik Cynthia M, Termorshuizen Jet D, Clinton David
University Health Care Research Center, Faculty of Medicine and Health, Örebro University, Örebro.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Psychiatr Genet. 2025 Apr 21. doi: 10.1097/YPG.0000000000000395.
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.
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.
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.
Qualitative research can capture the phenotypic expression of genetic risk, enrich GWAS, characterize heterogeneity, and inform development of genetically informed interventions.
全基因组关联研究（GWAS）表明，精神、代谢和人体测量因素与神经性厌食症有关。我们开发了一种“体验遗传学”设计，在GWAS之上叠加定性方法，以捕捉神经性厌食症的主观体验。
我们从神经性厌食症多基因风险评分（PRS）最高（n = 10）和最低（n = 10）的GWAS参与者中随机选择患有神经性厌食症的参与者。对PRS分组不知情的临床医生进行了半结构化访谈，探讨对症状、发病、病程以及负能量平衡（NEB）（即消耗的能量超过摄入的能量这一神经性厌食症的特征性症状）的身体和心理体验的认知。盲评人员对访谈记录进行评分；通过主题分析确定体验主题和子主题。
主题表明，高PRS组报告的终生精神问题更多，将陷入神经性厌食症描述为先前存在的先占观念的有目的进展，将NEB体验为更积极且充满活力，并且在访谈时更常出现症状；对他们来说，神经性厌食症似乎代表了以饮食失调特征和症状为中心的生命轨迹的顶点。低PRS组报告的终生精神问题较少，发病受环境因素影响更大，极端症状较少，并且在访谈时症状较少；对他们来说，神经性厌食症似乎构成了他们生命轨迹的短暂中断。访谈者猜对分组的频率低于随机概率（43%），这让人质疑通常与神经性厌食症相关的维度是否捕捉到了神经性厌食症的遗传本质。
定性研究可以捕捉遗传风险的表型表达，丰富GWAS，刻画异质性，并为基于遗传学的干预措施的开发提供信息。
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