Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types.
Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types.
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DOI：
10.1038/s41588-018-0081-4
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发表时间：
2018-04
期刊：
影响因子：
30.8
通讯作者：
Price AL
中科院分区：
文献类型：
--
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
我们介绍了一种通过分析基因表达数据和全基因组关联研究（GWAS）汇总统计来识别疾病相关组织和细胞类型的方法。我们的方法使用分层LD评分回归来测试疾病遗传性是否在给定组织中具有最高特异性表达的基因周围区域富集。我们将我们的方法应用于来自多个来源的基因表达数据以及48种疾病和性状的GWAS汇总统计（平均N=169K），检测到34种性状的显著组织特异性富集（FDR<5%）。在我们对多种组织的分析中，我们检测到广泛的富集，概括了已知的生物学。在我们的脑特异性和免疫特异性分析中，显著富集包括双相情感障碍的抑制性神经元超过兴奋性神经元，但精神分裂症和体重指数的兴奋性神经元超过抑制性神经元。我们的研究结果表明，我们的多基因方法是一个强大的方式来利用基因表达数据解释GWAS信号。
We introduce an approach for identifying disease-relevant tissues and cell types by analyzing gene expression data together with genome-wide association study (GWAS) summary statistics. Our approach uses stratified LD score regression to test whether disease heritability is enriched in regions surrounding genes with the highest specific expression in a given tissue. We apply our approach to gene expression data from several sources together with GWAS summary statistics for 48 diseases and traits (average N=169K), detecting significant tissue-specific enrichments (FDR<5%) for 34 traits. In our analysis of multiple tissues, we detect a broad range of enrichments that recapitulate known biology. In our brain-specific and immune-specific analyses, significant enrichments include an enrichment of inhibitory over excitatory neurons for bipolar disorder but excitatory over inhibitory neurons for schizophrenia and body mass index. Our results demonstrate that our polygenic approach is a powerful way to leverage gene expression data for interpreting GWAS signal.
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影响因子：
64.8
作者：
Ernst, Jason;Kheradpour, Pouya;Mikkelsen, Tarjei S.;Shoresh, Noam;Ward, Lucas D.;Epstein, Charles B.;Zhang, Xiaolan;Wang, Li;Issner, Robbyn;Coyne, Michael;Ku, Manching;Durham, Timothy;Kellis, Manolis;Bernstein, Bradley E.
通讯作者：
Bernstein, Bradley E.
影响因子：
16.6
作者：
Cordell HJ;Han Y;Mells GF;Li Y;Hirschfield GM;Greene CS;Xie G;Juran BD;Zhu D;Qian DC;Floyd JA;Morley KI;Prati D;Lleo A;Cusi D;Canadian-US PBC Consortium;Italian PBC Genetics Study Group;UK-PBC Consortium;Gershwin ME;Anderson CA;Lazaridis KN;Invernizzi P;Seldin MF;Sandford RN;Amos CI;Siminovitch KA
通讯作者：
Siminovitch KA
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：
64.5
作者：
Boyle EA;Li YI;Pritchard JK
通讯作者：
Pritchard JK