Abstract
BackgroundConsidering the implication of gene expression in the susceptibility of chronic diseases and the familial clustering of chronic diseases, the study of familial resemblances in gene expression levels is then highly relevant. Few studies have considered the contribution of both genetic and common environmental effects to familial resemblances in whole blood gene expression levels. The objective is to quantify the contribution of genetic and common environmental effects in the familial resemblances of whole blood genome-wide gene expression levels. We also make comparisons with familial resemblances in blood leukocytes genome-wide DNA methylation levels in the same cohort in order to further investigate biological mechanisms.ResultsMaximal heritability, genetic heritability, and common environmental effect were computed for all probes (20.6%, 15.6%, and 5.0% respectively) and for probes showing a significant familial effect (78.1%, 60.1%, and 18.0% respectively). Pairwise phenotypic correlations between gene expression and DNA methylation levels adjusted for blood cell heterogeneity were computed for probes showing significant familial effect. A total of 78 probe pairs among the 7,618,401 possible pairs passed Bonferroni correction (corrected P-value = 6.56 × 10− 9). Significant genetic correlations between gene expression and DNA methylation levels were found for 25 probe pairs (absolute genetic correlation of 0.97).ConclusionsFamilial resemblances in gene expression levels were mainly attributable to genetic factors, but common environmental effect also played a role especially in probes showing a significant familial effect. Probes and CpG sites with familial effect seem to be under a strong shared genetic control.
Highlights
Considering the implication of gene expression in the susceptibility of chronic diseases and the familial clustering of chronic diseases, the study of familial resemblances in gene expression levels is highly relevant
A study by our group in French Canadians showed that familial resemblances in blood leukocytes genome-wide DNA methylation levels are mainly attributable to genetic factors, but that common environmental effect plays a role [16]
When considering gene expression levels adjusted for blood cell heterogeneity of all probes (n = 18,160), we obtained a mean maximal heritability of 20.6%, a genetic heritability of 15.6%, and a common environmental effect of 5.0% (Table 2)
Summary
Considering the implication of gene expression in the susceptibility of chronic diseases and the familial clustering of chronic diseases, the study of familial resemblances in gene expression levels is highly relevant. Few studies have considered the contribution of both genetic and common environmental effects to familial resemblances in whole blood gene expression levels. The objective is to quantify the contribution of genetic and common environmental effects in the familial resemblances of whole blood genome-wide gene expression levels. The study of the inheritance patterns and familial resemblances of gene expression is highly relevant to better understand the origin of these diseases. Several studies have assessed the role of genetic factors on gene expression and DNA methylation [10,11,12]. A study by our group in French Canadians showed that familial resemblances in blood leukocytes genome-wide DNA methylation levels are mainly attributable to genetic factors, but that common environmental effect plays a role [16]. A study by Shakhbazov et al demonstrated a strong, shared genetic control for DNA methylation and gene expression [17]
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