Heritability enrichment in context-specific regulatory networks improves phenotype-relevant tissue identification

KIZ OpenIR > 科研部门 > 比较基因组学（宿兵）

	Heritability enrichment in context-specific regulatory networks improves phenotype-relevant tissue identification
	Feng, ZY; Duren, Z; Xin, JX; Yuan, QY; He, YX; Su, B; Wong, WH; Wang, Y
	2022
发表期刊	ELIFE
ISSN	2050-084X
卷号	11
摘要	Systems genetics holds the promise to decipher complex traits by interpreting their associated SNPs through gene regulatory networks derived from comprehensive multi-omics data of cell types, tissues, and organs. Here, we propose SpecVar to integrate paired chromatin accessibility and gene expression data into context-specific regulatory network atlas and regulatory categories, conduct heritability enrichment analysis with genome-wide association studies (GWAS) summary statistics, identify relevant tissues, and estimate relevance correlation to depict common genetic factors acting in the shared regulatory networks between traits. Our method improves power upon existing approaches by associating SNPs with context-specific regulatory elements to assess heritability enrichments and by explicitly prioritizing gene regulations underlying relevant tissues. Ablation studies, independent data validation, and comparison experiments with existing methods on GWAS of six phenotypes show that SpecVar can improve heritability enrichment, accurately detect relevant tissues, and reveal causal regulations. Furthermore, SpecVar correlates the relevance patterns for pairs of phenotypes and better reveals shared SNP-associated regulations of phenotypes than existing methods. Studying GWAS of 206 phenotypes in UK Biobank demonstrates that SpecVar leverages the context-specific regulatory network atlas to prioritize phenotypes' relevant tissues and shared heritability for biological and therapeutic insights. SpecVar provides a powerful way to interpret SNPs via context-specific regulatory networks.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/13541
专题	科研部门_比较基因组学（宿兵）
推荐引用方式 GB/T 7714	Feng, ZY,Duren, Z,Xin, JX,et al. Heritability enrichment in context-specific regulatory networks improves phenotype-relevant tissue identification[J]. ELIFE,2022,11.
APA	Feng, ZY.,Duren, Z.,Xin, JX.,Yuan, QY.,He, YX.,...&Wang, Y.(2022).Heritability enrichment in context-specific regulatory networks improves phenotype-relevant tissue identification.ELIFE,11.
MLA	Feng, ZY,et al."Heritability enrichment in context-specific regulatory networks improves phenotype-relevant tissue identification".ELIFE 11(2022).

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2023030816.pdf（1909KB）	期刊论文	出版稿	开放获取	CC BY-NC-SA	请求全文