Expression quantitative trait loci: present and future

The last few years have seen the development of large efforts for the analysis of genome function, especially in the context of genome variation. One of the most prominent directions has been the extensive set of studies on expression quantitative trait loci (eQTLs), namely, the discovery of genetic variants that explain variation in gene expression levels. Such studies have offered promise not just for the characterization of functional sequence variation but also for the understanding of basic processes of gene regulation and interpretation of genome-wide association studies. In this review, we discuss some of the key directions of eQTL research and its implications.

[1]  L. Kruglyak,et al.  Genetic Dissection of Transcriptional Regulation in Budding Yeast , 2002, Science.

[2]  Kazuya Iwamoto,et al.  Expression of HSPF1 and LIM in the lymphoblastoid cells derived from patients with bipolar disorder and schizophrenia , 2004, Journal of Human Genetics.

[3]  John D. Storey,et al.  Genetic interactions between polymorphisms that affect gene expression in yeast , 2005, Nature.

[4]  C. Wijmenga,et al.  Reconstruction of a functional human gene network, with an application for prioritizing positional candidate genes. , 2006, American journal of human genetics.

[5]  D. Stephan,et al.  A survey of genetic human cortical gene expression , 2007, Nature Genetics.

[6]  Stephen T Warren,et al.  Genome-wide expression profiling of lymphoblastoid cell lines distinguishes different forms of autism and reveals shared pathways. , 2007, Human molecular genetics.

[7]  Joseph T. Glessner,et al.  A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene , 2007, Nature.

[8]  L. Almasy,et al.  Discovery of expression QTLs using large-scale transcriptional profiling in human lymphocytes , 2007, Nature Genetics.

[9]  L. Liang,et al.  A genome-wide association study of global gene expression , 2007, Nature Genetics.

[10]  D. Koller,et al.  Population genomics of human gene expression , 2007, Nature Genetics.

[11]  Joshua T. Burdick,et al.  Common genetic variants account for differences in gene expression among ethnic groups , 2007, Nature Genetics.

[12]  Gonçalo R. Abecasis,et al.  Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma , 2007, Nature.

[13]  Simon C. Potter,et al.  Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls , 2007, Nature.

[14]  Simon Heath,et al.  Novel Crohn Disease Locus Identified by Genome-Wide Association Maps to a Gene Desert on 5p13.1 and Modulates Expression of PTGER4 , 2007, PLoS genetics.

[15]  John D. Storey,et al.  Gene-expression variation within and among human populations. , 2007, American journal of human genetics.

[16]  G. Wray The evolutionary significance of cis-regulatory mutations , 2007, Nature Reviews Genetics.

[17]  D. Busam,et al.  An Integrated Genomic Analysis of Human Glioblastoma Multiforme , 2008, Science.

[18]  E. Dermitzakis,et al.  Using gene expression to investigate the genetic basis of complex disorders. , 2008, Human molecular genetics.

[19]  Geoffrey Hom,et al.  Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX. , 2008, The New England journal of medicine.

[20]  A. Clark,et al.  Regulatory changes underlying expression differences within and between Drosophila species , 2008, Nature Genetics.

[21]  K. Shianna,et al.  Tissue-Specific Genetic Control of Splicing: Implications for the Study of Complex Traits , 2008, PLoS biology.

[22]  Bjarni V. Halldórsson,et al.  Many sequence variants affecting diversity of adult human height , 2008, Nature Genetics.

[23]  D. Reich,et al.  Effects of cis and trans Genetic Ancestry on Gene Expression in African Americans , 2008, PLoS genetics.

[24]  Judy H. Cho,et al.  Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease , 2008, Nature Genetics.

[25]  John D. Storey,et al.  A Genome-Wide Gene Expression Signature of Environmental Geography in Leukocytes of Moroccan Amazighs , 2008, PLoS genetics.

[26]  John D. Storey,et al.  Mapping the Genetic Architecture of Gene Expression in Human Liver , 2008, PLoS biology.

[27]  H. Stefánsson,et al.  Genetics of gene expression and its effect on disease , 2008, Nature.

[28]  G. Parmigiani,et al.  Core Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses , 2008, Science.

[29]  S. Horvath,et al.  Variations in DNA elucidate molecular networks that cause disease , 2008, Nature.

[30]  P. Deloukas,et al.  Common Regulatory Variation Impacts Gene Expression in a Cell Type–Dependent Manner , 2009, Science.

[31]  L. Liang,et al.  Mapping complex disease traits with global gene expression , 2009, Nature Reviews Genetics.

[32]  E. Schadt Molecular networks as sensors and drivers of common human diseases , 2009, Nature.

[33]  Christian Gieger,et al.  Six new loci associated with body mass index highlight a neuronal influence on body weight regulation , 2009, Nature Genetics.

[34]  R. Guigó,et al.  Transcriptome genetics using second generation sequencing in a Caucasian population , 2010, Nature.

[35]  E. Dermitzakis,et al.  Candidate Causal Regulatory Effects by Integration of Expression QTLs with Complex Trait Genetic Associations , 2010, PLoS genetics.

[36]  Teri A Manolio,et al.  Genomewide association studies and assessment of the risk of disease. , 2010, The New England journal of medicine.

[37]  Mark I. McCarthy,et al.  Identification of an imprinted master trans-regulator at the KLF14 locus related to multiple metabolic phenotypes , 2011, Nature Genetics.

[38]  Simon C. Potter,et al.  The Architecture of Gene Regulatory Variation across Multiple Human Tissues: The MuTHER Study , 2011, PLoS genetics.

[39]  P. Deloukas,et al.  Patterns of Cis Regulatory Variation in Diverse Human Populations , 2012, PLoS genetics.

[40]  Simon C. Potter,et al.  Mapping cis- and trans-regulatory effects across multiple tissues in twins , 2012, Nature Genetics.

[41]  Christian Gieger,et al.  Discovery and fine mapping of serum protein loci through transethnic meta-analysis. , 2012, American journal of human genetics.