Joint eQTL assessment of whole blood and dura mater tissue from individuals with Chiari type I malformation.

Lock, Eric F

Soldano, Karen L

Garrett, Melanie E

Cope, Heidi

Markunas, Christina A

Fuchs, Herbert

Grant, Gerald

Dunson, David B

Gregory, Simon G

Ashley-Koch, Allison E

England

2017-10-01T21:17:50Z

2017-10-01T21:17:50Z

2015-01-22

BACKGROUND: Expression quantitative trait loci (eQTL) play an important role in the regulation of gene expression. Gene expression levels and eQTLs are expected to vary from tissue to tissue, and therefore multi-tissue analyses are necessary to fully understand complex genetic conditions in humans. Dura mater tissue likely interacts with cranial bone growth and thus may play a role in the etiology of Chiari Type I Malformation (CMI) and related conditions, but it is often inaccessible and its gene expression has not been well studied. A genetic basis to CMI has been established; however, the specific genetic risk factors are not well characterized. RESULTS: We present an assessment of eQTLs for whole blood and dura mater tissue from individuals with CMI. A joint-tissue analysis identified 239 eQTLs in either dura or blood, with 79% of these eQTLs shared by both tissues. Several identified eQTLs were novel and these implicate genes involved in bone development (IPO8, XYLT1, and PRKAR1A), and ribosomal pathways related to marrow and bone dysfunction, as potential candidates in the development of CMI. CONCLUSIONS: Despite strong overall heterogeneity in expression levels between blood and dura, the majority of cis-eQTLs are shared by both tissues. The power to detect shared eQTLs was improved by using an integrative statistical approach. The identified tissue-specific and shared eQTLs provide new insight into the genetic basis for CMI and related conditions.

https://www.ncbi.nlm.nih.gov/pubmed/25609184

s12864-014-1211-8

1471-2164

https://hdl.handle.net/10161/15599

eng

Springer Science and Business Media LLC

BMC Genomics

10.1186/s12864-014-1211-8

Adolescent

Arnold-Chiari Malformation

Bone Development

Child

Child, Preschool

Cyclic AMP-Dependent Protein Kinase RIalpha Subunit

Dura Mater

Female

Gene Regulatory Networks

Genotype

Humans

Male

Pentosyltransferases

Polymorphism, Single Nucleotide

Quantitative Trait Loci

beta Karyopherins

Joint eQTL assessment of whole blood and dura mater tissue from individuals with Chiari type I malformation.

Journal article

Grant, Gerald|0000-0002-2651-4603

Gregory, Simon G|0000-0002-7805-1743

Ashley-Koch, Allison E|0000-0001-5409-9155

https://www.ncbi.nlm.nih.gov/pubmed/25609184

11

Basic Science Departments

Biostatistics & Bioinformatics

Center for Child and Family Policy

Clinical Science Departments

Duke

Duke Cancer Institute

Duke Institute for Brain Sciences

Duke Molecular Physiology Institute

Electrical and Computer Engineering

Institutes and Centers

Institutes and Provost's Academic Units

Medicine

Medicine, Nephrology

Molecular Genetics and Microbiology

Neurology

Neurology, MS & Neuroimmunology

Neurosurgery

Pathology

Pediatrics

Pratt School of Engineering

Sanford School of Public Policy

School of Medicine

Staff

Statistical Science

Trinity College of Arts & Sciences

University Institutes and Centers

Published online

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