Major depressive disorder (MDD) is clinically heterogeneous with prevalence rates twice as high in women as in men. There are many possible sources of heterogeneity in MDD most of which are not measured in a sufficiently comparable way across study samples. Here, we assess genetic heterogeneity based on two fundamental measures, between-cohort and between-sex heterogeneity. First, we used genome-wide association study (GWAS) summary statistics to investigate between-cohort genetic heterogeneity using the 29 research cohorts of the Psychiatric Genomics Consortium (PGC; N cases = 16,823, N controls = 25,632) and found that some of the cohort heterogeneity can be attributed to ascertainment differences (such as recruitment of cases from hospital vs. community sources). Second, we evaluated between-sex genetic heterogeneity using GWAS summary statistics from the PGC, Kaiser Permanente GERA, UK Biobank, and the Danish iPSYCH studies but did not find convincing evidence for genetic differences between the sexes. We conclude that there is no evidence that the heterogeneity between MDD data sets and between sexes reflects genetic heterogeneity. Larger sample sizes with detailed phenotypic records and genomic data remain the key to overcome heterogeneity inherent in assessment of MDD.

中文翻译：

---

量化重度抑郁症的队列间和性别间遗传异质性。


重度抑郁症（MDD）在临床上具有异质性，女性的患病率是男性的两倍。 MDD 中存在许多可能的异质性来源，其中大多数在研究样本中没有以足够可比的方式进行测量。在这里，我们根据两个基本指标评估遗传异质性：队列间异质性和性别间异质性。首先，我们使用全基因组关联研究 (GWAS) 汇总统计数据，利用精神病基因组学联盟 (PGC；N 个病例 = 16,823，N 个对照 = 25,632) 的 29 个研究队列来调查队列间遗传异质性，并发现一些队列异质性可归因于确定差异（例如从医院与社区来源招募病例）。其次，我们使用 PGC、Kaiser Permanente GERA、英国生物银行和丹麦 iPSYCH 研究的 GWAS 摘要统计数据评估了性别间遗传异质性，但没有找到性别间遗传差异的令人信服的证据。我们的结论是，没有证据表明 MDD 数据集之间以及性别之间的异质性反映了遗传异质性。更大的样本量以及详细的表型记录和基因组数据仍然是克服 MDD 评估中固有的异质性的关键。