Cell type-specific genetic regulation of gene expression across human tissues
Por:
Kim-Hellmuth, S, Aguet, F, Oliva, M, Munoz-Aguirre, M, Wucher, V, Kasela, S, Castel, SE, Hamel, AR, Vinuela, A, Roberts, AL, Mangul, S, Wen, XQ, Wang, G, Barbeira, AN, Garrido-Martin, D, Nadel, B, Zou, YX, Bonazzola, R, Quan, J, Brown, A, Martinez-Perez, A, Soria, JM, Getz, G, Dermitzakis, ET, Small, KS, Stephens, M, Xi, HS, Im, HK, Guig, R, Segr, AV, Stranger, BE, Ardlie, KG, Lappalainen, T
Publicada:
11 sep 2020
Resumen:
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.
Filiaciones:
Kim-Hellmuth, S:
Max Planck Inst Psychiat, Stat Genet, Munich, Germany
New York Genome Ctr, New York, NY 10013 USA
Columbia Univ, Dept Syst Biol, New York, NY 10032 USA
Univ Hosp LMU Munich, Dr von Hauser Childrens Hosp, Dept Pediat, Munich, Germany
Aguet, F:
Broad Inst MIT & Harvard, Cambridge, MA 02142 USA
Oliva, M:
Univ Chicago, Sect Genet Med, Dept Med, Chicago, IL USA
Univ Chicago, Dept Publ Hlth Sci, Chicago, IL USA
Munoz-Aguirre, M:
Barcelona Inst Sci & Technol, Ctr Genom Regulat CRG, Barcelona, Catalonia, Spain
Univ Politecn Catalunya UPC, Dept Stat & Operat Res, Barcelona, Catalonia, Spain
Wucher, V:
New York Genome Ctr, New York, NY 10013 USA
Columbia Univ, Dept Syst Biol, New York, NY 10032 USA
Kasela, S:
Barcelona Inst Sci & Technol, Ctr Genom Regulat CRG, Barcelona, Catalonia, Spain
Castel, SE:
New York Genome Ctr, New York, NY 10013 USA
Columbia Univ, Dept Syst Biol, New York, NY 10032 USA
Hamel, AR:
Broad Inst MIT & Harvard, Cambridge, MA 02142 USA
Ocular Genom Inst, Massachusetts Eye & Ear, Harvard Med Sch, Boston, MA USA
Vinuela, A:
Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England
Univ Geneva, Dept Genet Med & Dev, Med Sch, Geneva, Switzerland
Univ Geneva, Inst Genet & Genom Geneva iGE3, Geneva, Switzerland
Swiss Inst Bioinformat, Geneva, Switzerland
Roberts, AL:
Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England
Mangul, S:
Univ Calif Los Angeles, Dept Comp Sci, Los Angeles, CA 90024 USA
Univ Southern Calif Los Angeles, Dept Clin Pharm, Sch Pharm, Los Angeles, CA USA
Wen, XQ:
Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA
Wang, G:
Univ Chicago, Dept Human Genet, Chicago, IL USA
Barbeira, AN:
Univ Chicago, Sect Genet Med, Dept Med, Chicago, IL USA
Garrido-Martin, D:
Barcelona Inst Sci & Technol, Ctr Genom Regulat CRG, Barcelona, Catalonia, Spain
Nadel, B:
Univ Calif Los Angeles, Dept Mol Cellular Dev Biol, Los Angeles, CA USA
Zou, YX:
Univ Chicago, Dept Stat, Chicago, IL 60637 USA
Bonazzola, R:
Univ Chicago, Sect Genet Med, Dept Med, Chicago, IL USA
Quan, J:
Inflammat & Immunol Pfizer, Cambridge, MA USA
Brown, A:
Univ Geneva, Dept Genet Med & Dev, Med Sch, Geneva, Switzerland
Univ Dundee, Populat Hlth & Genom, Dundee, Scotland
Martinez-Perez, A:
Inst Invest Biomed St Pau IIB St PAU, Unit Genom Complex Dis, Barcelona, Spain
Soria, JM:
Inst Invest Biomed St Pau IIB St PAU, Unit Genom Complex Dis, Barcelona, Spain
Getz, G:
Broad Inst MIT & Harvard, Cambridge, MA 02142 USA
Massachusetts Gen Hosp, Canc Ctr, Boston, MA USA
Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA
Harvard Med Sch, Boston, MA 02115 USA
Dermitzakis, ET:
Univ Geneva, Dept Genet Med & Dev, Med Sch, Geneva, Switzerland
Univ Geneva, Inst Genet & Genom Geneva iGE3, Geneva, Switzerland
Swiss Inst Bioinformat, Geneva, Switzerland
Small, KS:
Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England
Stephens, M:
Univ Chicago, Dept Human Genet, Chicago, IL USA
Xi, HS:
Fdn Neurosci Ctr, AbbVie, Cambridge, MA USA
Im, HK:
Univ Chicago, Sect Genet Med, Dept Med, Chicago, IL USA
Guig, R:
Barcelona Inst Sci & Technol, Ctr Genom Regulat CRG, Barcelona, Catalonia, Spain
Univ Pompeu Fabra UPF, Barcelona, Spain
Segr, AV:
Broad Inst MIT & Harvard, Cambridge, MA 02142 USA
Ocular Genom Inst, Massachusetts Eye & Ear, Harvard Med Sch, Boston, MA USA
Stranger, BE:
Univ Chicago, Sect Genet Med, Dept Med, Chicago, IL USA
Northwestern Univ, Ctr Genet Med, Dept Pharmacol, Feinberg Sch Med, Chicago, IL USA
Ardlie, KG:
Broad Inst MIT & Harvard, Cambridge, MA 02142 USA
Lappalainen, T:
New York Genome Ctr, New York, NY 10013 USA
Columbia Univ, Dept Syst Biol, New York, NY 10032 USA
Bronze, Green Accepted
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