Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
School of Psychology and Counselling, Queensland University of Technology, Brisbane, Australia.
Am J Med Genet B Neuropsychiatr Genet. 2019 Sep;180(6):439-447. doi: 10.1002/ajmg.b.32713. Epub 2019 Feb 1.
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.
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 有许多可能的异质来源，其中大多数在研究样本之间没有以足够可比的方式进行测量。在这里，我们基于两个基本指标评估遗传异质性，即组间和性别间异质性。首先，我们使用全基因组关联研究（GWAS）汇总统计数据，通过精神病学基因组学联盟（PGC）的 29 个研究队列（N 病例=16823，N 对照=25632）调查组间遗传异质性，发现一些队列异质性可归因于确认差异（例如从医院还是社区来源招募病例）。其次，我们使用 PGC、Kaiser Permanente GERA、英国生物银行和丹麦 iPSYCH 研究的 GWAS 汇总统计数据评估性别间遗传异质性，但没有发现性别间存在遗传差异的可靠证据。我们得出的结论是，没有证据表明 MDD 数据集之间的异质性和性别之间的异质性反映了遗传异质性。更大的样本量，带有详细表型记录和基因组数据，仍然是克服 MDD 评估中固有异质性的关键。
