Applying polygenic risk scores to postpartum depression
Applying polygenic risk scores to postpartum depression
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DOI：
10.1007/s00737-014-0428-5
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发表时间：
2014-12-01
影响因子：
4.5
通讯作者：
Wray, Naomi R.
中科院分区：
文献类型：
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作者：
Byrne, Enda M.;Carrillo-Roa, Tania;Wray, Naomi R.
重性抑郁障碍（MDD）的病因可能是异质性的，但产后抑郁症（PPD）被假设为代表一个更同质的MDD子集。我们使用全基因组SNP数据来探索这一假设。我们收集了来自澳大利亚、荷兰、瑞典和英国的1，420例自我报告的PPD病例和9，473例全基因组基因型对照。我们估计了归因于基因型变异的总方差。我们使用来自精神病学基因组学联盟（PGC）的双相情感障碍（BPD）和MDD的关联结果，在PPD和相关MDD数据集中创建多基因评分，以估计疾病之间的遗传重叠。我们估计，由常见遗传变异解释的责任量表的方差百分比为0.22，标准误为0.12，p = 0.02。所有四个队列中PPD病例/对照状态的逻辑回归的方差（R（2））的比例在通过PGC-BPD关联结果加权的SNP谱评分上很小（0.1%）但显著（p = 0.004），表明BPD和PPD之间的遗传重叠。结果在澳大利亚和荷兰队列中非常显著（R（2）> 1.1%，p < 0.008），其中大多数病例符合MDD标准。在排除PPD病例后，在较大的澳大利亚和荷兰MDD病例/对照队列中，BPD和MDD之间的遗传重叠不显著（R（2）= 0.06%，p = 0.08），尽管较大的MDD组提供了更大的把握度。我们的研究结果表明，BPD和PPD之间比BPD和MDD之间更重要的共同遗传病因的经验遗传学证据。
The etiology of major depressive disorder (MDD) is likely to be heterogeneous, but postpartum depression (PPD) is hypothesized to represent a more homogenous subset of MDD. We use genome-wide SNP data to explore this hypothesis. We assembled a total cohort of 1,420 self-report cases of PPD and 9,473 controls with genome-wide genotypes from Australia, The Netherlands, Sweden and the UK. We estimated the total variance attributable to genotyped variants. We used association results from the Psychiatric Genomics Consortia (PGC) of bipolar disorder (BPD) and MDD to create polygenic scores in PPD and related MDD data sets to estimate the genetic overlap between the disorders. We estimated that the percentage of variance on the liability scale explained by common genetic variants to be 0.22 with a standard error of 0.12, p = 0.02. The proportion of variance (R (2)) from a logistic regression of PPD case/control status in all four cohorts on a SNP profile score weighted by PGC-BPD association results was small (0.1 %) but significant (p = 0.004) indicating a genetic overlap between BPD and PPD. The results were highly significant in the Australian and Dutch cohorts (R (2) > 1.1 %, p < 0.008), where the majority of cases met criteria for MDD. The genetic overlap between BPD and MDD was not significant in larger Australian and Dutch MDD case/control cohorts after excluding PPD cases (R (2) = 0.06 %, p = 0.08), despite the larger MDD group affording more power. Our results suggest an empirical genetic evidence for a more important shared genetic etiology between BPD and PPD than between BPD and MDD.