最小表型分析對重度抑鬱症會產生低特異性的全基因組關聯信號

最小表型分析對重度抑鬱症會產生低特異性的全基因組關聯信號

作者：

小柯機器人

發布時間：2020/3/31 13:17:14

德國亥姆霍茲聯合會Na Cai等研究人員發現，最小表型分析對重度抑鬱症會產生低特異性的全基因組關聯信號。2020年3月30日，《自然—遺傳學》雜誌在線發表了這項成果。

研究人員報導了由最小表型定義的抑鬱症和嚴格定義的重度抑鬱障礙（MDD）之間的遺傳結構差異：前者具有較低的基因型遺傳性，與嚴格定義的MDD相比，不能用輕症病例來解釋，而在其他條件下導致這種共有遺傳原因的基因組比例更高。

 

基於最小表型定義的GWAS可優先識別非MDD特異的基因座，儘管它會產生高度預測的多基因風險評分，但預測力完全可以通過大樣本量來解釋，而不是通過對MDD的特異性。這些結果表明，依賴最小表型的結果可能會左右對MDD遺傳結構的看法，並阻礙對MDD特異性途徑的鑑定。

 

據悉，最小表型是指依靠少量自報告項目進行疾病病例識別，並越來越多地用於GWAS。

 

附：英文原文

Title: Minimal phenotyping yields genome-wide association signals of low specificity for major depression

Author: Na Cai, Joana A. Revez, Mark J. Adams, Till F. M. Andlauer, Gerome Breen, Enda M. Byrne, Toni-Kim Clarke, Andreas J. Forstner, Hans J. Grabe, Steven P. Hamilton, Douglas F. Levinson, Cathryn M. Lewis, Glyn Lewis, Nicholas G. Martin, Yuri Milaneschi, Ole Mors, Bertram Mller-Myhsok, Brenda W. J. H. Penninx, Roy H. Perlis, Giorgio Pistis, James B. Potash, Martin Preisig, Jianxin Shi, Jordan W. Smoller, Fabien Streit, Henning Tiemeier, Rudolf Uher, Sandra Van der Auwera, Alexander Viktorin, Myrna M. Weissman, Kenneth S. Kendler, Jonathan Flint

Issue&Volume: 2020-03-30

Abstract: Minimal phenotyping refers to the reliance on the use of a small number of self-reported items for disease case identification, increasingly used in genome-wide association studies (GWAS). Here we report differences in genetic architecture between depression defined by minimal phenotyping and strictly defined major depressive disorder (MDD): the former has a lower genotype-derived heritability that cannot be explained by inclusion of milder cases and a higher proportion of the genome contributing to this shared genetic liability with other conditions than for strictly defined MDD. GWAS based on minimal phenotyping definitions preferentially identifies loci that are not specific to MDD, and, although it generates highly predictive polygenic risk scores, the predictive power can be explained entirely by large sample sizes rather than by specificity for MDD. Our results show that reliance on results from minimal phenotyping may bias views of the genetic architecture of MDD and impede the ability to identify pathways specific to MDD.

DOI: 10.1038/s41588-020-0594-5

Source: https://www.nature.com/articles/s41588-020-0594-5