NEW YORK – New findings from an international research team are highlighting the importance of including individuals from diverse human populations and ancestry groups when searching for genetic contributors to major depression.

纽约——一个国际研究团队的新发现突显了在寻找导致严重抑郁症的遗传因素时，将来自不同人群和祖先群体的个体包括在内的重要性。

'The diversity, in combination with the large sample size, enabled a comparison of the causal genetic architecture across ancestry groups,' corresponding author Karoline Kuchenbaecker, a professor of genetic epidemiology at University College London, and her colleagues wrote in Nature Genetics on Thursday..

通讯作者、伦敦大学学院遗传流行病学教授卡罗琳·库琴巴克尔（KarolineKuchenbaecker）及其同事周四在《自然遗传学》（Nature Genetics）上写道：“多样性与大样本量相结合，可以比较不同祖先群体的因果遗传结构。”。。

The researchers searched for genetic factors linked to major depression within and across ancestry groups with a genome-wide association study and GWAS meta-analysis involving more than 88,300 cases and nearly 902,800 controls — including participants of African, East Asian, South Asian, and Hispanic/Latin American ancestry enrolled through several distinct research cohorts — before bringing in published data for 258,364 more cases and 571,252 controls of European descent..

研究人员通过全基因组关联研究和GWAS荟萃分析，在祖先群体内和祖先群体之间寻找与抑郁症相关的遗传因素，该研究涉及88300多例病例和近902800例对照，其中包括非洲，东亚，南亚，西班牙裔/拉丁美洲血统通过几个不同的研究队列登记，然后再提供258364例病例和571252例欧洲血统对照的公布数据。。

From there, the team went on to perform fine-mapping analysis and gene prioritization. These were informed by 354 gene associations found in a transcriptome-wide association study done with expression data for major depression-related tissues. They also used 'Multi-marker Analysis of Genomic Annotation' (MAGMA) methods with or without Hi-C and conducted analyses with the 'functional mapping and annotation' (FUMA) platform..

从那时起，该团队继续进行精细定位分析和基因优先排序。在一项针对抑郁症相关组织表达数据的转录组关联研究中，发现了354个基因关联。他们还使用了有或没有Hi-C的“基因组注释的多标记分析”（MAGMA）方法，并使用“功能作图和注释”（FUMA）平台进行了分析。。

All told, the investigators narrowed in on 190 genome-wide significant associations with major depression, falling at 160 distinct genetic loci, including 53 not described in the past.

总的来说，研究人员缩小了190个全基因组与抑郁症的显着关联，下降到160个不同的基因位点，其中53个在过去没有描述过。

While the results validated many of the associations reported in Europeans in the past, the authors pointed out that 'a notable proportion of [major depression] loci are specific to samples of European ancestry.' On the other hand, they explained, a subset of associations appeared to be specific to the multi-ancestry meta-analysis..

虽然这些结果验证了过去欧洲人报告的许多关联，但作者指出，“相当一部分（重度抑郁症）基因座是欧洲血统样本特有的。”另一方面，他们解释说，一部分关联似乎是多血统荟萃分析特有的。。

'We identified novel, biologically plausible associations that were missed in European ancestry analyses and demonstrated that large, diverse samples can be important for identifying target genes and putative mechanisms,' the authors reported. 'These findings suggest that for [major depression], a heterogeneous condition with highly complex etiology, increasing ancestral as well as global diversity in genetic studies may be particularly important to ensure discovery of core genes and to inform about transferability of findings across ancestry groups.'.

作者报告说：“我们发现了欧洲血统分析中遗漏的新颖的、生物学上合理的关联，并证明了大量多样的样本对于鉴定靶基因和推定机制可能很重要。”这些发现表明，对于[重性抑郁症]，病因高度复杂，遗传研究中祖先和全球多样性增加的异质性疾病对于确保核心基因的发现并告知祖先群体之间发现的可转移性可能特别重要。

For example, the search led to a previously unappreciated association involving the chromosome 2 locus 2q24.2 in Hispanic/Latin American participants and a chromosome 6 locus linked to brain cortex expression of the melanin-concentrating hormone gene MCHR2 that showed more tenuous ties to major depression in African ancestry participants..

例如，该搜索导致了一个以前未被认可的关联，涉及西班牙裔/拉丁美洲参与者的2号染色体2q24.2位点和一个与黑色素浓缩激素基因MCHR2大脑皮层表达相关的6号染色体位点，该基因与非洲血统参与者的重性抑郁症关系更为微弱。。

The team also went on to compare fine-mapping features in the multi-ancestry group and in Europeans, flagging 155 loci linked to major depression at a genome-wide significant level across ancestry groups, while prioritizing 43 genes of interest using TWAS, MAGMA, HiC-MAGMA, and FUMA approaches.

该团队还继续比较了多血统组和欧洲人的精细定位特征，在祖先组中以全基因组显着水平标记了155个与抑郁症相关的基因座，同时使用TWAS，MAGMA，HiC MAGMA和FUMA方法对43个感兴趣的基因进行了优先排序。

While the authors cautioned that '[i]t is possible that some of the 190 genome-wide significant loci we identified are linked to a more general susceptibility to mental illness instead of being specific to [major depression],' they suggested that 'given the overlap between different psychiatric disorders, such findings are nevertheless of value for our understanding of the biology and for the development of new treatments for [major depression].'.

虽然作者警告说，“我们确定的190个全基因组重要基因座中的一些可能与更普遍的精神疾病易感性有关，而不是特定于[重度抑郁症]，”他们建议“鉴于不同精神疾病之间的重叠，然而，这些发现对于我们对生物学的理解以及[重度抑郁症]新疗法的开发具有价值。”。