title: Gene-gene and gene-environment interactions detected by transcriptome sequence analysis in twins.
abstract: Understanding the genetic architecture of gene expression is an intermediate step in understanding the genetic architecture of complex diseases. RNA sequencing technologies have improved the quantification of gene expression and allow measurement of allele-specific expression (ASE). ASE is hypothesized to result from the direct effect of cis regulatory variants, but a proper estimation of the causes of ASE has not been performed thus far. In this study, we take advantage of a sample of twins to measure the relative contributions of genetic and environmental effects to ASE, and we find substantial effects from gene × gene (G×G) and gene × environment (G×E) interactions. We propose a model where ASE requires genetic variability in cis, a difference in the sequence of both alleles, but where the magnitude of the ASE effect depends on trans genetic and environmental factors that interact with the cis genetic variants.
authors.affiliation: 1] Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland. [2] Institute of Genetics and Genomics in Geneva, University of Geneva, Geneva, Switzerland. [3] Swiss Institute of Bioinformatics, Geneva, Switzerland.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Buil
authors.affiliation: 1] Human Genetics, Wellcome Trust Sanger Institute, Hinxton, UK. [2] NORMENT, KG Jebsen Center for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
authors.forename: Andrew Anand
authors.initials: AA
authors.lastname: Brown
authors.affiliation: 1] Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland. [2] Institute of Genetics and Genomics in Geneva, University of Geneva, Geneva, Switzerland. [3] Swiss Institute of Bioinformatics, Geneva, Switzerland. [4] Department of Genetics, Stanford University, Stanford, California, USA.
authors.forename: Tuuli
authors.initials: T
authors.lastname: Lappalainen
authors.affiliation: Department of Twin Research, King's College London, London, UK.
authors.forename: Ana
authors.identifier: 0000000337718537
authors.initials: A
authors.lastname: Viñuela
authors.affiliation: Department of Twin Research, King's College London, London, UK.
authors.forename: Matthew N
authors.initials: MN
authors.lastname: Davies
authors.affiliation: 1] Department of Medicine, McGill University, Montreal, Quebec, Canada. [2] Department of Human Genetics, McGill University, Montreal, Quebec, Canada. [3] Department of Epidemiology and Biostatistics, McGill University, Montreal, Quebec, Canada.
authors.forename: Hou-Feng
authors.initials: HF
authors.lastname: Zheng
authors.affiliation: 1] Department of Twin Research, King's College London, London, UK. [2] Department of Medicine, McGill University, Montreal, Quebec, Canada. [3] Department of Human Genetics, McGill University, Montreal, Quebec, Canada. [4] Department of Epidemiology and Biostatistics, McGill University, Montreal, Quebec, Canada.
authors.forename: J Brent
authors.initials: JB
authors.lastname: Richards
authors.affiliation: Department of Twin Research, King's College London, London, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Glass
authors.affiliation: Department of Twin Research, King's College London, London, UK.
authors.forename: Kerrin S
authors.initials: KS
authors.lastname: Small
authors.affiliation: Human Genetics, Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Durbin
authors.affiliation: Department of Twin Research, King's College London, London, UK.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Spector
authors.affiliation: 1] Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland. [2] Institute of Genetics and Genomics in Geneva, University of Geneva, Geneva, Switzerland. [3] Swiss Institute of Bioinformatics, Geneva, Switzerland.
authors.forename: Emmanouil T
authors.initials: ET
authors.lastname: Dermitzakis
mesh_terms: D000483:Alleles; D001483:Base Sequence; D004843:Epistasis, Genetic / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics*; D005787:Gene Frequency; D059647:Gene-Environment Interaction; D014644:Genetic Variation; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008957:Models, Genetic; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D012333:RNA, Messenger / Q000096:biosynthesis; D017423:Sequence Analysis, RNA; D059467:Transcriptome; D014429:Twins, Dizygotic / Q000235:genetics*; D014430:Twins, Monozygotic / Q000235:genetics*
chemical_list: D012333:RNA, Messenger