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

Alfonso Buil; Andrew Anand Brown; Tuuli Lappalainen; Ana Viñuela; Matthew N Davies; Hou-Feng Zheng; J Brent Richards; Daniel Glass; Kerrin S Small; Richard Durbin; Timothy D Spector; Emmanouil T Dermitzakis

doi:10.1038/ng.3162

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

Alfonso Buil (Lead / Corresponding author), Andrew Anand Brown, Tuuli Lappalainen, Ana Viñuela, Matthew N Davies, Hou-Feng Zheng, J Brent Richards, Daniel Glass, Kerrin S Small, Richard Durbin, Timothy D Spector, Emmanouil T Dermitzakis (Lead / Corresponding author)

Population Health and Genomics

Research output: Contribution to journal › Article › peer-review

132 Citations (Scopus)

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.

Original language	English
Pages (from-to)	88-91
Number of pages	4
Journal	Nature Genetics
Volume	47
Issue number	1
Early online date	1 Dec 2014
DOIs	https://doi.org/10.1038/ng.3162
Publication status	Published - Jan 2015

Keywords

Alleles
Base Sequence
Epistasis, Genetic/genetics
Female
Gene Expression Profiling
Gene Expression Regulation/genetics
Gene Frequency
Gene-Environment Interaction
Genetic Variation
Haplotypes/genetics
Humans
Models, Genetic
Molecular Sequence Data
Polymorphism, Single Nucleotide
Quantitative Trait Loci
RNA, Messenger/biosynthesis
Sequence Analysis, RNA
Transcriptome
Twins, Dizygotic/genetics
Twins, Monozygotic/genetics

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10.1038/ng.3162

Brown, Andrew
- Population Health and Genomics - Principal Investigator (Tenure Track)
Person: Academic

Cite this

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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. ",

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author = "Alfonso Buil and Brown, {Andrew Anand} and Tuuli Lappalainen and Ana Vi{\~n}uela and Davies, {Matthew N} and Hou-Feng Zheng and Richards, {J Brent} and Daniel Glass and Small, {Kerrin S} and Richard Durbin and Spector, {Timothy D} and Dermitzakis, {Emmanouil T}",

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doi = "10.1038/ng.3162",

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journal = "Nature Genetics",

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AU - Buil, Alfonso

AU - Brown, Andrew Anand

AU - Lappalainen, Tuuli

AU - Viñuela, Ana

AU - Davies, Matthew N

AU - Zheng, Hou-Feng

AU - Richards, J Brent

AU - Glass, Daniel

AU - Small, Kerrin S

AU - Durbin, Richard

AU - Spector, Timothy D

AU - Dermitzakis, Emmanouil T

PY - 2015/1

Y1 - 2015/1

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AB - 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.

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KW - Base Sequence

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KW - Female

KW - Gene Expression Profiling

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KW - Gene-Environment Interaction

KW - Genetic Variation

KW - Haplotypes/genetics

KW - Humans

KW - Models, Genetic

KW - Molecular Sequence Data

KW - Polymorphism, Single Nucleotide

KW - Quantitative Trait Loci

KW - RNA, Messenger/biosynthesis

KW - Sequence Analysis, RNA

KW - Transcriptome

KW - Twins, Dizygotic/genetics

KW - Twins, Monozygotic/genetics

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DO - 10.1038/ng.3162

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VL - 47

SP - 88

EP - 91

JO - Nature Genetics

JF - Nature Genetics

IS - 1

ER -

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

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Keywords

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Brown, Andrew

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