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Sökning: WFRF:(Aguet Francois) > (2024) > Interaction molecul...

Interaction molecular QTL mapping discovers cellular and environmental modifiers of genetic regulatory effects

Kasela, Silva (författare)
New York Genome Center, New York, NY, USA; Department of Systems Biology, Columbia University, New York, NY, USA
Aguet, François (författare)
Broad Institute of MIT and Harvard, Cambridge, MA, USA
Kim-Hellmuth, Sarah (författare)
New York Genome Center, New York, NY, USA; Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital LMU Munich, Munich, Germany; Computational Health Center, Institute of Translational Genomics, Helmholtz Munich, Neuherberg, Germany
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Brown, Brielin C. (författare)
New York Genome Center, New York, NY, USA; Data Science Institute, Columbia University, New York, NY, USA
Nachun, Daniel C. (författare)
Department of Pathology, Stanford University, Stanford, CA, USA
Tracy, Russell P. (författare)
Pathology and Laboratory Medicine, The University of Vermont, Larner College of Medicine, Burlington, VT, USA
Durda, Peter (författare)
Pathology and Laboratory Medicine, The University of Vermont, Larner College of Medicine, Burlington, VT, USA
Liu, Yongmei (författare)
Department of Medicine, Duke University, Durham, NC, USA
Taylor, Kent D. (författare)
The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA
Johnson, W. Craig (författare)
Department of Biostatistics, University of Washington, Seattle, WA, USA
Van Den Berg, David (författare)
Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, USA
Gabriel, Stacey (författare)
Broad Institute of MIT and Harvard, Cambridge, MA, USA
Gupta, Namrata (författare)
Broad Institute of MIT and Harvard, Cambridge, MA, USA
Smith, Joshua D. (författare)
Northwest Genomics Center, University of Washington, Seattle, WA, USA
Blackwell, Thomas W. (författare)
Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA
Rotter, Jerome I. (författare)
The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA
Ardlie, Kristin G. (författare)
Broad Institute of MIT and Harvard, Cambridge, MA, USA
Manichaikul, Ani (författare)
Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA
Rich, Stephen S. (författare)
Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA
Barr, R. Graham (författare)
Departments of Medicine and Epidemiology, Columbia University Medical Center, New York, NY, USA
Lappalainen, Tuuli (författare)
KTH,Genteknologi,Science for Life Laboratory, SciLifeLab,New York Genome Center, New York, NY, USA; Department of Systems Biology, Columbia University, New York, NY, USA
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 (creator_code:org_t)
Elsevier BV, 2024
2024
Engelska.
Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 111:1, s. 133-149
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • Bulk-tissue molecular quantitative trait loci (QTLs) have been the starting point for interpreting disease-associated variants, and context-specific QTLs show particular relevance for disease. Here, we present the results of mapping interaction QTLs (iQTLs) for cell type, age, and other phenotypic variables in multi-omic, longitudinal data from the blood of individuals of diverse ancestries. By modeling the interaction between genotype and estimated cell-type proportions, we demonstrate that cell-type iQTLs could be considered as proxies for cell-type-specific QTL effects, particularly for the most abundant cell type in the tissue. The interpretation of age iQTLs, however, warrants caution because the moderation effect of age on the genotype and molecular phenotype association could be mediated by changes in cell-type composition. Finally, we show that cell-type iQTLs contribute to cell-type-specific enrichment of diseases that, in combination with additional functional data, could guide future functional studies. Overall, this study highlights the use of iQTLs to gain insights into the context specificity of regulatory effects.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

Nyckelord

cell-type composition
DNA methylation
gene expression
gene-environment interaction
interaction QTL

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