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Congruence of Additive and Non-Additive Effects on Gene Expression Estimated from Pedigree and SNP Data
- Source :
- PLOS Genetics, Vol. 9, No 5 (2013) P. e1003502, PLoS Genetics, PLoS Genetics, Vol 9, Iss 5, p e1003502 (2013)
- Publication Year :
- 2013
-
Abstract
- There is increasing evidence that heritable variation in gene expression underlies genetic variation in susceptibility to disease. Therefore, a comprehensive understanding of the similarity between relatives for transcript variation is warranted—in particular, dissection of phenotypic variation into additive and non-additive genetic factors and shared environmental effects. We conducted a gene expression study in blood samples of 862 individuals from 312 nuclear families containing MZ or DZ twin pairs using both pedigree and genotype information. From a pedigree analysis we show that the vast majority of genetic variation across 17,994 probes is additive, although non-additive genetic variation is identified for 960 transcripts. For 180 of the 960 transcripts with non-additive genetic variation, we identify expression quantitative trait loci (eQTL) with dominance effects in a sample of 339 unrelated individuals and replicate 31% of these associations in an independent sample of 139 unrelated individuals. Over-dominance was detected and replicated for a trans association between rs12313805 and ETV6, located 4MB apart on chromosome 12. Surprisingly, only 17 probes exhibit significant levels of common environmental effects, suggesting that environmental and lifestyle factors common to a family do not affect expression variation for most transcripts, at least those measured in blood. Consistent with the genetic architecture of common diseases, gene expression is predominantly additive, but a minority of transcripts display non-additive effects.<br />Author Summary Gene expression levels are known to influence common disease susceptibility in humans, with GWAS significant SNPs frequently found in regulatory regions. The expression levels of most genes are influenced by genetic variants, often located close to the gene itself. Expression Quantitative Trait Loci (eQTL) mapping studies have been very successful in identifying SNPs associated with expression levels; however, little is currently known about the extent of additive and non-additive genetic variance and the role of common environment on gene expression. Here we report a comprehensive study of the sources of genetic and non-genetic variation for gene expression levels using both pedigree and genotype information. We show that the majority of transcripts exhibit only additive genetic variance with congruence from independent methods using pedigree and genotype approaches. However, there are a small number of probes whose expression levels are influenced by non-additive genetic variance. For some of these probes we identify SNPs acting in a dominant and over-dominant manner that replicate in an independent sample. Surprisingly, only 17 probes exhibit significant levels of common environmental effects, suggesting that environmental and lifestyle factors common to a family do not affect expression variation for most transcripts, at least those measured in blood.
- Subjects :
- Male
Cancer Research
Gene Expression
Genetic Networks
Transcriptomes
Genotype
Twins, Dizygotic
ddc:576.5
Genetics (clinical)
Genetics
0303 health sciences
education.field_of_study
030305 genetics & heredity
Chromosome Mapping
Genomics
Middle Aged
Genome Scans
Pedigree
Female
Research Article
Adult
medicine.medical_specialty
lcsh:QH426-470
Population
Quantitative Trait Loci
Quantitative trait locus
Biology
Genome Complexity
Polymorphism, Single Nucleotide
03 medical and health sciences
Genetic linkage
Genome Analysis Tools
Molecular genetics
Genetic variation
medicine
Genome-Wide Association Studies
Humans
Genetic Predisposition to Disease
education
Trait Locus Analysis
Molecular Biology
Ecology, Evolution, Behavior and Systematics
Genetic Association Studies
030304 developmental biology
Aged
Twins, Monozygotic
Genetic architecture
lcsh:Genetics
Genetics, Population
Expression quantitative trait loci
Genome Expression Analysis
Subjects
Details
- Language :
- English
- ISSN :
- 15537390
- Database :
- OpenAIRE
- Journal :
- PLOS Genetics, Vol. 9, No 5 (2013) P. e1003502, PLoS Genetics, PLoS Genetics, Vol 9, Iss 5, p e1003502 (2013)
- Accession number :
- edsair.doi.dedup.....a3a478c5b7b5729b9dd8382feec440dd