%0 Journal Article %J Science %D 2020 %T Cell type-specific genetic regulation of gene expression across human tissues. %A Kim-Hellmuth, Sarah %A Aguet, François %A Oliva, Meritxell %A Muñoz-Aguirre, Manuel %A Kasela, Silva %A Wucher, Valentin %A Castel, Stephane E %A Hamel, Andrew R %A Viñuela, Ana %A Roberts, Amy L %A Mangul, Serghei %A Wen, Xiaoquan %A Wang, Gao %A Barbeira, Alvaro N %A Garrido-Martín, Diego %A Nadel, Brian B %A Zou, Yuxin %A Bonazzola, Rodrigo %A Quan, Jie %A Brown, Andrew %A Martinez-Perez, Angel %A Soria, José Manuel %A Getz, Gad %A Dermitzakis, Emmanouil T %A Small, Kerrin S %A Stephens, Matthew %A Xi, Hualin S %A Im, Hae Kyung %A Guigo, Roderic %A Segrè, Ayellet V %A Stranger, Barbara E %A Ardlie, Kristin G %A Lappalainen, Tuuli %K Cells %K Gene Expression Regulation %K Humans %K Organ Specificity %K Quantitative Trait Loci %K RNA, Long Noncoding %K Transcriptome %X

The Genotype-Tissue Expression (GTEx) project has identified expression and splicing quantitative trait loci in cis (QTLs) for the majority of genes across a wide range of human tissues. However, the functional characterization of these QTLs has been limited by the heterogeneous cellular composition of GTEx tissue samples. We mapped interactions between computational estimates of cell type abundance and genotype to identify cell type-interaction QTLs for seven cell types and show that cell type-interaction expression QTLs (eQTLs) provide finer resolution to tissue specificity than bulk tissue cis-eQTLs. Analyses of genetic associations with 87 complex traits show a contribution from cell type-interaction QTLs and enables the discovery of hundreds of previously unidentified colocalized loci that are masked in bulk tissue.

%B Science %V 369 %8 2020 09 11 %G eng %N 6509 %1 https://www.ncbi.nlm.nih.gov/pubmed/32913075?dopt=Abstract %R 10.1126/science.aaz8528 %0 Journal Article %J Science %D 2020 %T The impact of sex on gene expression across human tissues. %A Oliva, Meritxell %A Muñoz-Aguirre, Manuel %A Kim-Hellmuth, Sarah %A Wucher, Valentin %A Gewirtz, Ariel D H %A Cotter, Daniel J %A Parsana, Princy %A Kasela, Silva %A Balliu, Brunilda %A Viñuela, Ana %A Castel, Stephane E %A Mohammadi, Pejman %A Aguet, François %A Zou, Yuxin %A Khramtsova, Ekaterina A %A Skol, Andrew D %A Garrido-Martín, Diego %A Reverter, Ferran %A Brown, Andrew %A Evans, Patrick %A Gamazon, Eric R %A Payne, Anthony %A Bonazzola, Rodrigo %A Barbeira, Alvaro N %A Hamel, Andrew R %A Martinez-Perez, Angel %A Soria, José Manuel %A Pierce, Brandon L %A Stephens, Matthew %A Eskin, Eleazar %A Dermitzakis, Emmanouil T %A Segrè, Ayellet V %A Im, Hae Kyung %A Engelhardt, Barbara E %A Ardlie, Kristin G %A Montgomery, Stephen B %A Battle, Alexis J %A Lappalainen, Tuuli %A Guigo, Roderic %A Stranger, Barbara E %K Chromosomes, Human, X %K Disease %K Epigenesis, Genetic %K Female %K Gene Expression %K Gene Expression Regulation %K Genetic Variation %K Genome-Wide Association Study %K Humans %K Male %K Organ Specificity %K Promoter Regions, Genetic %K Quantitative Trait Loci %K Sex Characteristics %K Sex Factors %X

Many complex human phenotypes exhibit sex-differentiated characteristics. However, the molecular mechanisms underlying these differences remain largely unknown. We generated a catalog of sex differences in gene expression and in the genetic regulation of gene expression across 44 human tissue sources surveyed by the Genotype-Tissue Expression project (GTEx, v8 release). We demonstrate that sex influences gene expression levels and cellular composition of tissue samples across the human body. A total of 37% of all genes exhibit sex-biased expression in at least one tissue. We identify cis expression quantitative trait loci (eQTLs) with sex-differentiated effects and characterize their cellular origin. By integrating sex-biased eQTLs with genome-wide association study data, we identify 58 gene-trait associations that are driven by genetic regulation of gene expression in a single sex. These findings provide an extensive characterization of sex differences in the human transcriptome and its genetic regulation.

%B Science %V 369 %8 2020 09 11 %G eng %N 6509 %1 https://www.ncbi.nlm.nih.gov/pubmed/32913072?dopt=Abstract %R 10.1126/science.aba3066