TY - JOUR
T1 - A characterization of cis- and trans-heritability of RNA-Seq-based gene expression
AU - Ouwens, Klaasjan G
AU - Jansen, Rick
AU - Nivard, Michel G
AU - van Dongen, Jenny
AU - Frieser, Maia J
AU - Hottenga, Jouke-Jan
AU - Arindrarto, Wibowo
AU - Claringbould, Annique
AU - van Iterson, Maarten
AU - Mei, Hailiang
AU - Franke, Lude
AU - Heijmans, Bastiaan T
AU - A C 't Hoen, Peter
AU - van Meurs, Joyce
AU - Brooks, Andrew I
AU - Penninx, Brenda W J H
AU - Boomsma, Dorret I
AU - BIOS Consortium
PY - 2020/2
Y1 - 2020/2
N2 - Insights into individual differences in gene expression and its heritability (h2)
can help in understanding pathways from DNA to phenotype. We estimated
the heritability of gene expression of 52,844 genes measured in whole
blood in the largest twin RNA-Seq sample to date (1497 individuals
including 459 monozygotic twin pairs and 150 dizygotic twin pairs) from
classical twin modeling and identity-by-state-based approaches. We
estimated for each gene h2total, composed of cis-heritability (h2cis, the variance explained by single nucleotide polymorphisms in the cis-window of the gene), and trans-heritability (h2res, the residual variance explained by all other genome-wide variants). Mean h2total
was 0.26, which was significantly higher than heritability estimates
earlier found in a microarray-based study using largely overlapping
(>60%) RNA samples (mean h2 = 0.14, p = 6.15 × 10−258). Mean h2cis was 0.06 and strongly correlated with beta of the top cis expression quantitative loci (eQTL, ρ = 0.76, p < 10−308) and with estimates from earlier RNA-Seq-based studies. Mean h2res was 0.20 and correlated with the beta of the corresponding trans-eQTL (ρ = 0.04, p < 1.89 × 10−3) and was significantly higher for genes involved in cytokine-cytokine interactions (p = 4.22 × 10−15),
many other immune system pathways, and genes identified in genome-wide
association studies for various traits including behavioral disorders
and cancer. This study provides a thorough characterization of cis- and trans-h2 estimates of gene expression, which is of value for interpretation of GWAS and gene expression studies.
AB - Insights into individual differences in gene expression and its heritability (h2)
can help in understanding pathways from DNA to phenotype. We estimated
the heritability of gene expression of 52,844 genes measured in whole
blood in the largest twin RNA-Seq sample to date (1497 individuals
including 459 monozygotic twin pairs and 150 dizygotic twin pairs) from
classical twin modeling and identity-by-state-based approaches. We
estimated for each gene h2total, composed of cis-heritability (h2cis, the variance explained by single nucleotide polymorphisms in the cis-window of the gene), and trans-heritability (h2res, the residual variance explained by all other genome-wide variants). Mean h2total
was 0.26, which was significantly higher than heritability estimates
earlier found in a microarray-based study using largely overlapping
(>60%) RNA samples (mean h2 = 0.14, p = 6.15 × 10−258). Mean h2cis was 0.06 and strongly correlated with beta of the top cis expression quantitative loci (eQTL, ρ = 0.76, p < 10−308) and with estimates from earlier RNA-Seq-based studies. Mean h2res was 0.20 and correlated with the beta of the corresponding trans-eQTL (ρ = 0.04, p < 1.89 × 10−3) and was significantly higher for genes involved in cytokine-cytokine interactions (p = 4.22 × 10−15),
many other immune system pathways, and genes identified in genome-wide
association studies for various traits including behavioral disorders
and cancer. This study provides a thorough characterization of cis- and trans-h2 estimates of gene expression, which is of value for interpretation of GWAS and gene expression studies.
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U2 - 10.1038/s41431-019-0511-5
DO - 10.1038/s41431-019-0511-5
M3 - Article
C2 - 31558840
SN - 1018-4813
VL - 28
SP - 253
EP - 263
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 2
ER -