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Nat Genet. 2015 Jan;47(1):88-91. doi: 10.1038/ng.3162. Epub 2014 Dec 1.

Gene-gene and gene-environment interactions detected by transcriptome sequence analysis in twins.

Author information

1
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.
2
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.
3
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.
4
Department of Twin Research, King's College London, London, UK.
5
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.
6
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.
7
Human Genetics, Wellcome Trust Sanger Institute, Hinxton, UK.

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.

PMID:
25436857
PMCID:
PMC4643454
DOI:
10.1038/ng.3162
[Indexed for MEDLINE]
Free PMC Article

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