Stratifying depression by neuroticism: revisiting a diagnostic tradition using GWAS data
Stratifying depression by neuroticism: revisiting a diagnostic tradition using GWAS data
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DOI：
10.1101/547828
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发表时间：
2019-02
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影响因子：
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通讯作者：
M. Adams;David Mark Howard;M. Luciano;Toni‐Kim Clarke;G. Davies;W. Hill;Danny J. Smith;I. Deary;D. Porteous;A. McIntosh
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作者：
M. Adams;David Mark Howard;M. Luciano;Toni‐Kim Clarke;G. Davies;W. Hill;Danny J. Smith;I. Deary;D. Porteous;A. McIntosh
重度抑郁症和神经质有很大的遗传基础。我们试图确定这种共享基础是否可以分解，以确定抑郁症特有的遗传因素。我们分析了来自抑郁症全基因组关联研究（来自精神病基因组学联盟和23andMe）的两组汇总统计数据，并将其与神经质的GWAS（来自英国生物银行）进行了比较。首先，我们使用成对GWAS分析将变异分类为仅与抑郁症相关，仅与神经质相关，或两者兼而有之。其次，我们估计了部分遗传相关性，以测试抑郁症与其他表型的遗传联系是否可以通过与神经质的共同重叠来解释。我们发现证据表明，大多数与抑郁症相关的遗传变异可能与神经质相同。抑郁症和神经质的重叠共同遗传变异与认知功能呈负遗传相关，与几种精神疾病呈正遗传相关。我们发现，抑郁症特有的遗传贡献与炎症、心血管疾病和睡眠模式有关，而与神经质无关。我们的研究结果表明，虽然抑郁症的遗传危险因素在很大程度上与神经质共享，但也有非神经质相关的抑郁症特征，可能对进一步的患者或表型分层有用。
Major depressive disorder and neuroticism share a large genetic basis. We sought to determine whether this shared basis could be decomposed to identify genetic factors that are specific to depression. We analysed two sets of summary statistics from genome-wide association studies of depression (from the Psychiatric Genomics Consortium and 23andMe) and compared them to GWAS of neuroticism (from UK Biobank). First, we used a pairwise GWAS analysis to classify variants as associated with only depression, with only neuroticism, or with both. Second, we estimated partial genetic correlations to test whether the depression’s genetic link with other phenotypes was explained by shared overlap with neuroticism. We found evidence that most genetic variants associated with depression are likely to be shared with neuroticism. The overlapping common genetic variance of depression and neuroticism was negatively genetically correlated with cognitive function and positively genetically correlated with several psychiatric disorders. We found that the genetic contributions unique to depression, and not shared with neuroticism, were correlated with inflammation, cardiovascular disease, and sleep patterns. Our findings demonstrate that, while genetic risk factors for depression are largely shared with neuroticism, there are also non-neuroticism related features of depression that may be useful for further patient or phenotypic stratification.