Determining a diagnosis of major depressive disorder (MDD) is complex, involving consideration and rating of a variety of different components. These include number of symptoms over an agreed threshold, symptom duration, functional impairment, persistence of symptoms within an episode, and symptom recurrence. While these components are generally accepted amongst physicians, it is unknown whether they reflect partly distinct biology between phenotypes. The aim of this study was to investigate how the genetic aetiology varies in the presence of different MDD components. Thirty-two depression phenotypes which systematically incorporate the MDD components were created using the mental health questionnaire data within the UK Biobank. SNP-based heritabilities and genetic correlations with three previously defined major depression phenotypes were calculated (broad depression, Psychiatric Genomics Consortium (PGC) defined depression and 23andMe, Inc. self-reported depression) and differences between estimates analysed. All phenotypes were heritable (h2SNP range: 0.102 - 0.162) and showed substantial genetic correlations with other major depression phenotypes (Rg range: 0.651 - 0.894 (PGC); 0.652 - 0.837 (23andMe); 0.699 - 0.900 (broad depression)). The requirement for 5 or more symptoms and for a long episode duration had the strongest effect on SNP-based heritability, in the positive and negative direction respectively (1.4% average increase; 2.7% average decrease). No significant differences were noted between genetic correlations. While there is some variation, the two cardinal symptoms, depressed mood and anhedonia, largely reflect the genetic aetiology of phenotypes incorporating more MDD components. These components may appropriately index for severity, however, the genetic component between phenotypes incorporating none and all components is comparable.

中文翻译：

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什么是诊断？重大抑郁症的遗传分解。

确定重度抑郁症（MDD）的诊断很复杂，需要考虑和评估各种不同的成分。这些包括超过约定阈值的症状数量，症状持续时间，功能障碍，发作内症状持续存在和症状复发。尽管这些成分被医生普遍接受，但尚不清楚它们是否反映了表型之间的部分不同生物学特性。这项研究的目的是调查存在不同MDD成分时遗传病因如何变化。使用UK Biobank中的心理健康调查表数据创建了32种抑郁表型，这些表型系统地纳入了MDD成分。计算了基于SNP的遗传力和与三种先前定义的主要抑郁症表型的遗传相关性（广泛抑郁症，精神病基因组学联盟（PGC）定义的抑郁症和23andMe，Inc.自我报告的抑郁症），并分析了估计值之间的差异。所有表型都是可遗传的（h2SNP范围：0.102-0.162），并显示出与其他主要抑郁表型的显着遗传相关性（Rg范围：0.651-0.894（PGC）； 0.652-0.837（23andMe）； 0.699-0.900（广泛抑郁））。对5种或5种以上症状和较长发作时间的要求，分别对SNP遗传力的影响最大，分别在正向和负向（平均增加1.4％；平均减少2.7％）。遗传相关性之间没有显着差异。虽然有些差异，这两种主要症状，即情绪低落和快感不足，在很大程度上反映了结合更多MDD成分的表型的遗传病因。这些成分可以适当地指示严重性，但是，表型之间不包含所有成分的遗传成分是可比较的。