Integration of GWAS SNPs and tissue specific expression profiling reveal discrete eQTLs for human traits in blood and brain

Neurobiology of Disease

Mike A. Nalls¹  Michael E. Weale¹  J. Raphael Gibbs²  Robert Walker³  Bryan J. Traynor⁴  Stefania Bandinelli⁴  Richard O'Brien⁵  Alan B. Zonderman⁶  Mina Ryten⁶  Andrew B. Singleton⁷  John Hardy⁷  Mark R. Cookson⁸  Dena G. Hernandez⁹  Daniah Trabzuni⁹  Juan Troncoso⁹  Sean Chong⁹  Matthew Moore⁹  Sampath Arepalli⁹  Allissa Dillman⁹  Colin Smith^1,10 

[1] Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK;Department of Neuroscience, Karolinska Institute, 171 77 Stockholm, Sweden;Molecular Genetics, King's College London, UK;Brain Resource Center, Johns Hopkins University, Baltimore, MD, USA;;Department of Medical &Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK;Department of Pathology, The University of Edinburgh, Wilkie Building, Teviot Place, Edinburgh, UK;Geriatric Unit, Azienda Sanitaria Firenze (ASF), Florence, Italy;Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA;Research Resources Branch, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA;

关键词: eQTL;    GWAS;    Brain;    Blood;   

DOI  :  

来源: DOAJ

【 摘 要 】

Genome-wide association studies have nominated many genetic variants for common human traits, including diseases, but in many cases the underlying biological reason for a trait association is unknown. Subsets of genetic polymorphisms show a statistical association with transcript expression levels, and have therefore been nominated as expression quantitative trait loci (eQTL). However, many tissue and cell types have specific gene expression patterns and so it is not clear how frequently eQTLs found in one tissue type will be replicated in others. In the present study we used two appropriately powered sample series to examine the genetic control of gene expression in blood and brain. We find that while many eQTLs associated with human traits are shared between these two tissues, there are also examples where blood and brain differ, either by restricted gene expression patterns in one tissue or because of differences in how genetic variants are associated with transcript levels. These observations suggest that design of eQTL mapping experiments should consider tissue of interest for the disease or other traits studied.

【 授权许可】

Unknown