title: Joint eQTL assessment of whole blood and dura mater tissue from individuals with Chiari type I malformation.
abstract: 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.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC, USA. Eric.F.Lock@gmail.com.|Department of Statistical Science, Duke University, Durham, NC, USA. Eric.F.Lock@gmail.com.
authors.forename: Eric F
authors.initials: EF
authors.lastname: Lock
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC, USA. karen.soldano@duke.edu.|Duke Center for Human Disease Modeling, Duke University Medical Center, Durham, NC, USA. karen.soldano@duke.edu.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Soldano
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC, USA. melanie.kail@duke.edu.|Duke Center for Human Disease Modeling, Duke University Medical Center, Durham, NC, USA. melanie.kail@duke.edu.
authors.forename: Melanie E
authors.initials: ME
authors.lastname: Garrett
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC, USA. heidi.cope@duke.edu.|Duke Center for Human Disease Modeling, Duke University Medical Center, Durham, NC, USA. heidi.cope@duke.edu.
authors.forename: Heidi
authors.initials: H
authors.lastname: Cope
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC, USA. christina.markunas@nih.gov.
authors.forename: Christina A
authors.initials: CA
authors.lastname: Markunas
authors.affiliation: Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, NC, USA. fuchs001@mc.duke.edu.
authors.forename: Herbert
authors.initials: H
authors.lastname: Fuchs
authors.affiliation: Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, NC, USA. ggrant2@stanford.edu.|Department of Neurosurgery, Stanford University/Lucile Packard Children's Hospital, Stanford, CA, USA. ggrant2@stanford.edu.
authors.forename: Gerald
authors.initials: G
authors.lastname: Grant
authors.affiliation: Department of Statistical Science, Duke University, Durham, NC, USA. dunson@duke.edu.
authors.forename: David B
authors.initials: DB
authors.lastname: Dunson
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC, USA. simon.gregory@duke.edu.|Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA. simon.gregory@duke.edu.
authors.forename: Simon G
authors.initials: SG
authors.lastname: Gregory
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC, USA. allison.AshleyKoch@duke.edu.|Duke Center for Human Disease Modeling, Duke University Medical Center, Durham, NC, USA. allison.AshleyKoch@duke.edu.
authors.forename: Allison E
authors.initials: AE
authors.lastname: Ashley-Koch
mesh_terms: D000293:Adolescent; D001139:Arnold-Chiari Malformation / Q000235:genetics* / Q000473:pathology; D001846:Bone Development / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / Q000097:blood / Q000235:genetics / Q000378:metabolism; D004388:Dura Mater / Q000378:metabolism; D005260:Female; D053263:Gene Regulatory Networks; D005838:Genotype; D006801:Humans; D008297:Male; D010430:Pentosyltransferases / Q000097:blood / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D028961:beta Karyopherins / Q000097:blood / Q000235:genetics / Q000378:metabolism; D000097608:UDP Xylose-Protein Xylosyltransferase
chemical_list: D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; D010430:Pentosyltransferases; D028961:beta Karyopherins; D000097608:UDP Xylose-Protein Xylosyltransferase; C107282:IPO8 protein, human; C517834:PRKAR1A protein, human