Mapping Open Chromatin to Understand Genetic Variants in Blood Traits
Author Information
Author(s): Paul Dirk S. Nisbet, James P. Yang, Stuart Meacham, Augusto Rendon, Katta Hautaviita, Jonna Tallila, Jacqui White, Marloes R. Tijssen, Suthesh Sivapalaratnam, Hanneke Basart, Mieke D. Trip, Berthold Göttgens, Nicole Soranzo, Willem H. Ouwehand, Panos Deloukas
Primary Institution: Wellcome Trust Sanger Institute
Hypothesis
Can maps of open chromatin help identify functional variants associated with hematological traits?
Conclusion
The study identified a specific genetic variant that affects platelet volume and function by altering transcription factor binding.
Supporting Evidence
- Open chromatin profiles were distinct between megakaryocytic and erythroblastoid cells.
- An open chromatin region at chromosome 7q22.3 was identified in megakaryocytes but not in erythroblasts.
- Resequencing of the open chromatin region in 643 individuals provided strong evidence for the causative variant rs342293.
- The C- and G-alleles of rs342293 differentially bind the transcription factor EVI1.
- Gene expression analysis showed that rs342293 affects PIK3CG gene expression in platelets and macrophages.
- Functional studies in Pik3cg knockout mice revealed significant differences in platelet-related gene expression.
Takeaway
Scientists looked at how certain parts of DNA that are open and active can help explain why some people have different blood traits. They found a specific change in DNA that affects how platelets work.
Methodology
The study used the FAIRE method to map open chromatin in megakaryocytic and erythroblastoid cell lines and analyzed genetic variants associated with hematological traits.
Limitations
The findings are based on a selected set of loci and may not be generalizable to the entire genome.
Participant Demographics
The study involved 643 individuals of Northern European ancestry.
Statistical Information
P-Value
p=0.047
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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