Genetic stratification of depression by neuroticism: revisiting a diagnostic tradition.
Genetic stratification of depression by neuroticism: revisiting a diagnostic tradition.
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DOI：
10.1017/s0033291719002629
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发表时间：
2020-11
影响因子：
6.9
通讯作者：
McIntosh AM
中科院分区：
文献类型：
--
作者：
Adams MJ;Howard DM;Luciano M;Clarke TK;Davies G;Hill WD;23andMe Research Team;Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium;Smith D;Deary IJ;Porteous DJ;McIntosh AM
重度抑郁症和神经症（Neu）有很大的遗传基础。我们试图确定这种共同的基础是否可以分解，以确定抑郁症特有的遗传因素。我们分析了抑郁症全基因组关联研究（GWAS）的汇总统计数据（来自精神病学基因组学联盟、23andMe和UK Biobank），并将其与Neu的GWAS（来自UK Biobank）进行了比较。首先，我们使用两两GWAS分析将变异分类为仅与抑郁相关、仅与Neu相关或两者都相关。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Neu的共享重叠来解释。我们发现证据表明，大多数与抑郁症相关的基因组区域（25/37）可能与Neu共享。抑郁症和抑郁症共同遗传变异的重叠主要与精神疾病相关。我们发现，与Neu不同的抑郁症遗传因素与代谢表型和心血管疾病呈正相关，与人格特质尽责性负相关。在去除与Neu共有的基因重叠后，抑郁症仍然与精神分裂症、双相情感障碍、冠状动脉疾病和头胎年龄有特定的关联。与抑郁症无关，Neu在溃疡性结肠炎、青春期生长、厌食症和教育方面具有特定的遗传相关性。我们的研究结果表明，尽管抑郁症的遗传风险因素在很大程度上与Neu相同，但也存在与Neu无关的抑郁症特征，这些特征可能对进一步的患者或表型分层有用。
Major depressive disorder and neuroticism (Neu) 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 summary statistics from genome-wide association studies (GWAS) of depression (from the Psychiatric Genomics Consortium, 23andMe and UK Biobank) and compared them with GWAS of Neu (from UK Biobank). First, we used a pairwise GWAS analysis to classify variants as associated with only depression, with only Neu 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 Neu. We found evidence that most genomic regions (25/37) associated with depression are likely to be shared with Neu. The overlapping common genetic variance of depression and Neu was genetically correlated primarily with psychiatric disorders. We found that the genetic contributions to depression, that were not shared with Neu, were positively correlated with metabolic phenotypes and cardiovascular disease, and negatively correlated with the personality trait conscientiousness. After removing shared genetic overlap with Neu, depression still had a specific association with schizophrenia, bipolar disorder, coronary artery disease and age of first birth. Independent of depression, Neu had specific genetic correlates in ulcerative colitis, pubertal growth, anorexia and education. Our findings demonstrate that, while genetic risk factors for depression are largely shared with Neu, there are also non-Neu-related features of depression that may be useful for further patient or phenotypic stratification.