Genetic Contribution to the Heterogeneity of Major Depressive Disorder: Evidence From a Sibling-Based Design Using Swedish National Registers.
Genetic Contribution to the Heterogeneity of Major Depressive Disorder: Evidence From a Sibling-Based Design Using Swedish National Registers.
复制标题
遗传对重度抑郁症异质性的贡献：来自使用瑞典国家登记册的基于兄弟姐妹的设计的证据。
DOI：
10.1176/appi.ajp.20220906
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Lu,Yi
中科院分区：
文献类型：
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作者：
Nguyen,Thuy-Dung;Kowalec,Kaarina;Pasman,Joëlle;Larsson,Henrik;Lichtenstein,Paul;Dalman,Christina;Sullivan,PatrickF;Kuja-Halkola,Ralf;Lu,Yi
重度抑郁症（MDD）是高度异质性的。标准的类型学部分地捕捉到了这种疾病的症状异质性，尽管它是否充分捕捉到了病因异质性仍然难以捉摸。本研究的目的是探讨MDD heterogeneity.MethodsUsing瑞典患者登记数据的150万人的遗传特征，作者确定了46,255个人与专家诊断的MDD。根据临床和心理社会特征定义的9个比较组确定了18个亚组，包括严重程度、复发、合并症、自杀倾向、损伤、残疾、监护室和诊断时的年龄。一个同胞为基础的设计和经典的定量遗传模型，估计遗传力的MDD亚组和亚组之间的遗传相关性。残疾和青年发病亚组的遗传度（55.1%-58.3%）显著高于总体MDD样本（45.3%，95%CI =43.0-47.5），单次发作MDD和无精神病合并症的亚组的估计值显著较低（30.5%-34.4%）。比较组内各亚组之间的遗传相关性估计值为0.33至0.90。九个遗传相关性中有七个显著小于1，表明潜在的遗传结构存在差异。这些结果在很大程度上是一致的，与以前的工作，使用基因组data.ConclusionsThe差异遗传力和部分不同的遗传成分在亚组的研究结果提供了重要的见解MDD的遗传异质性和更深层次的病因学了解MDD的临床亚组。
ObjectiveMajor depressive disorder (MDD) is highly heterogeneous. Standard typology partly captures the disorder’s symptomatic heterogeneity, although whether it adequately captures etiological heterogeneity remains elusive. The aim of this study was to investigate the genetic characterization of MDD heterogeneity.MethodsUsing Swedish patient register data on 1.5 million individuals, the authors identified 46,255 individuals with specialist-diagnosed MDD. Eighteen subgroups were identified based on nine comparison groups defined by clinical and psychosocial features, including severity, recurrence, comorbidities, suicidality, impairment, disability, care unit, and age at diagnosis. A sibling-based design and classic quantitative genetic models were applied to estimate heritability of MDD subgroups and genetic correlations between subgroups.ResultsEstimates of heritability ranged from 30.5% to 58.3% across subgroups. The disabled and youth-onset subgroups showed significantly higher heritability (55.1%–58.3%) than the overall MDD sample (45.3%, 95% CI=43.0–47.5), and the subgroups with single-episode MDD and without psychiatric comorbidity showed significantly lower estimates (30.5%–34.4%). Estimates of genetic correlations between the subgroups within comparison groups ranged from 0.33 to 0.90. Seven of nine genetic correlations were significantly smaller than 1, suggesting differences in underlying genetic architecture. These results were largely consistent with previous work using genomic data.ConclusionsThe findings of differential heritability and partially distinct genetic components in subgroups provide important insights into the genetic heterogeneity of MDD and a deeper etiological understanding of MDD clinical subgroups.