single-tissue and cross-tissue heritability of gene expression via identity-by-descent in related or unrelated individuals通过identity-by-descent single-tissue和cross-tissue遗传基因表达相关或无关的个人.pdfVIP

Single-Tissue and Cross-Tissue Heritability of Gene Expression Via Identity-by-Descent in Related or Unrelated Individuals 1,2,3 4,5 4 3,6 4 Alkes L. Price *, Agnar Helgason *, Gudmar Thorleifsson , Steven A. McCarroll , Augustine Kong , Kari Stefansson4,5* 1 Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America, 2 Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, United States of America, 3 Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, United States of America, 4 deCODE Genetics, Reykjavik, Iceland, 5 University of Iceland, Reykjavik, Iceland, 6 Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America Abstract Family studies of individual tissues have shown that gene expression traits are genetically heritable. Here, we investigate cis and trans components of heritability both within and across tissues by applying variance-components methods to 722 Icelanders from family cohorts, using identity-by-descent (IBD) estimates from long-range phased genome-wide SNP data and gene expression measurements for ,19,000 genes in blood and adipose tissue. We estimate the proportion of gene expression heritability attributable to cis regulation as 37% in blood and 24% in adipose tissue. Our results indicate that the correlation in gene expression measurements across these tissues is primarily due to heritability at cis loci, whereas there is little sharing of trans regulation across tissues. One implication of this finding is that heritability in tissues composed of heterogeneous cell types is expected to