最小表型分析对重度抑郁症会产生低特异性的全基因组关联信号
2020-04-03   阅读:656   来源:自然

德国亥姆霍兹联合会Na Cai等研究人员发现,最小表型分析对重度抑郁症会产生低特异性的全基因组关联信号。2020年3月30日,《自然—遗传学》杂志在线发表了这项成果。

研究人员报道了由最小表型定义的抑郁症和严格定义的重度抑郁障碍(MDD)之间的遗传结构差异:前者具有较低的基因型遗传性,与严格定义的MDD相比,不能用轻症病例来解释,而在其他条件下导致这种共有遗传原因的基因组比例更高。
 
基于最小表型定义的GWAS可优先识别非MDD特异的基因座,尽管它会产生高度预测的多基因风险评分,但预测力完全可以通过大样本量来解释,而不是通过对MDD的特异性。这些结果表明,依赖最小表型的结果可能会左右对MDD遗传结构的看法,并阻碍对MDD特异性途径的鉴定。
 
据悉,最小表型是指依靠少量自报告项目进行疾病病例识别,并越来越多地用于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

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