Minimal phenotyping yields genome-wide association signals of low specificity for major depression.
Minimal phenotyping yields genome-wide association signals of low specificity for major depression.
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DOI：
10.1038/s41588-020-0594-5
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发表时间：
2020-04
期刊：
影响因子：
30.8
通讯作者：
Flint J
中科院分区：
文献类型：
--
作者：
Cai N;Revez JA;Adams MJ;Andlauer TFM;Breen G;Byrne EM;Clarke TK;Forstner AJ;Grabe HJ;Hamilton SP;Levinson DF;Lewis CM;Lewis G;Martin NG;Milaneschi Y;Mors O;Müller-Myhsok B;Penninx BWJH;Perlis RH;Pistis G;Potash JB;Preisig M;Shi J;Smoller JW;Streit F;Tiemeier H;Uher R;Van der Auwera S;Viktorin A;Weissman MM;MDD Working Group of the Psychiatric Genomics Consortium;Kendler KS;Flint J
最小表型是指依赖于使用少量自我报告的项目进行疾病病例识别，越来越多地用于全基因组关联研究（GWAS）。在这里，我们报告了由最小表型定义的抑郁症和严格定义的重性抑郁症（MDD）之间的遗传结构差异：前者具有较低的基因型衍生的遗传力，这不能通过纳入较轻的病例来解释，并且与严格定义的MDD相比，基因组中更高的比例有助于与其他条件共享遗传易感性。基于最小表型定义的GWAS优先识别非MDD特异性的基因座，尽管它产生高度预测性的多基因风险评分，但预测能力完全可以通过大样本量而不是MDD特异性来解释。我们的研究结果表明，依赖于最小的表型分析结果可能会导致对MDD遗传结构的偏见，并阻碍识别MDD特异性通路的能力。
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.
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影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
影响因子：
30.8
作者：
Finucane HK;Bulik-Sullivan B;Gusev A;Trynka G;Reshef Y;Loh PR;Anttila V;Xu H;Zang C;Farh K;Ripke S;Day FR;ReproGen Consortium;Schizophrenia Working Group of the Psychiatric Genomics Consortium;RACI Consortium;Purcell S;Stahl E;Lindstrom S;Perry JR;Okada Y;Raychaudhuri S;Daly MJ;Patterson N;Neale BM;Price AL
通讯作者：
Price AL
影响因子：
30.8
作者：
Finucane HK;Reshef YA;Anttila V;Slowikowski K;Gusev A;Byrnes A;Gazal S;Loh PR;Lareau C;Shoresh N;Genovese G;Saunders A;Macosko E;Pollack S;Brainstorm Consortium;Perry JRB;Buenrostro JD;Bernstein BE;Raychaudhuri S;McCarroll S;Neale BM;Price AL
通讯作者：
Price AL
影响因子：
6.8
作者：
Corfield EC;Yang Y;Martin NG;Nyholt DR
通讯作者：
Nyholt DR