Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Biol Psychiatry. 2019 Oct 15;86(8):577-586. doi: 10.1016/j.biopsych.2019.04.036. Epub 2019 May 15.
Although attention-deficit/hyperactivity disorder (ADHD) and eating disorders (EDs) frequently co-occur, little is known about the shared etiology. In this study, we comprehensively investigated the genetic association between ADHD and various EDs, including anorexia nervosa (AN) and other EDs such as bulimia nervosa.
We applied different genetically informative designs to register-based information of a Swedish nationwide population (N = 3,550,118). We first examined the familial coaggregation of clinically diagnosed ADHD and EDs across multiple types of relatives. We then applied quantitative genetic modeling in full-sisters and maternal half-sisters to estimate the genetic correlations between ADHD and EDs. We further tested the associations between ADHD polygenic risk scores and ED symptoms, and between AN polygenic risk scores and ADHD symptoms, in a genotyped population-based sample (N = 13,472).
Increased risk of all types of EDs was found in individuals with ADHD (any ED: odds ratio [OR] = 3.97, 95% confidence interval [CI] = 3.81, 4.14; AN: OR = 2.68, 95% CI = 2.15, 2.86; other EDs: OR = 4.66, 95% CI = 4.47, 4.87; bulimia nervosa: OR = 5.01, 95% CI = 4.63, 5.41) and their relatives compared with individuals without ADHD and their relatives. The magnitude of the associations decreased as the degree of relatedness decreased, suggesting shared familial liability between ADHD and EDs. Quantitative genetic models revealed stronger genetic correlation of ADHD with other EDs (.37, 95% CI = .31, .42) than with AN (.14, 95% CI = .05, .22). ADHD polygenic risk scores correlated positively with ED symptom measures overall and with the subscales Drive for Thinness and Body Dissatisfaction despite small effect sizes.
We observed stronger genetic association with ADHD for non-AN EDs than for AN, highlighting specific genetic correlation beyond a general genetic factor across psychiatric disorders.
尽管注意力缺陷/多动障碍(ADHD)和饮食障碍(EDs)经常同时发生,但对于它们共同的病因知之甚少。在这项研究中,我们全面研究了 ADHD 与各种 EDs(包括神经性厌食症[AN]和其他 EDs,如神经性贪食症)之间的遗传关联。
我们应用不同的遗传信息设计,利用瑞典全国范围内的登记信息(N=3550118)。我们首先检查了临床诊断的 ADHD 和 EDs 在多种类型亲属之间的家族聚集情况。然后,我们在全姐妹和半同胞母亲中应用数量遗传学模型来估计 ADHD 和 EDs 之间的遗传相关性。我们进一步在基于基因分型的人群样本(N=13472)中测试了 ADHD 多基因风险评分与 ED 症状之间的关联,以及 AN 多基因风险评分与 ADHD 症状之间的关联。
患有 ADHD 的个体患所有类型 EDs 的风险增加(任何 ED:优势比[OR] = 3.97,95%置信区间[CI] = 3.81,4.14;AN:OR = 2.68,95% CI = 2.15,2.86;其他 EDs:OR = 4.66,95% CI = 4.47,4.87;贪食症:OR = 5.01,95% CI = 4.63,5.41)及其亲属与未患 ADHD 的个体及其亲属相比。随着亲缘关系的降低,关联的幅度减小,这表明 ADHD 和 EDs 之间存在共同的家族易感性。数量遗传模型显示,ADHD 与其他 EDs(.37,95%CI =.31,.42)的遗传相关性强于与 AN(.14,95%CI =.05,.22)。ADHD 多基因风险评分与 ED 症状测量值总体上呈正相关,与“追求消瘦”和“身体不满”的子量表也呈正相关,尽管效应量较小。
我们观察到 ADHD 与非 AN EDs 的遗传相关性更强,而非与 AN 的遗传相关性更强,这突出了精神障碍之间特定的遗传相关性,而不仅仅是一般的遗传因素。