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Over the last 10 years, genome‐wide association studies (GWAS) have identified hundreds of susceptibility loci for autoimmune diseases. However, despite increasing power for the detection of both common and rare coding variants affecting disease susceptibility, a large fraction of disease heritability has remained unexplained. In addition, a majority of the identified loci are located in noncoding...
Background DNA methylation is influenced by both environmental and genetic factors and is increasingly thought to affect variation in complex traits and diseases. Yet, the extent of ancestry-related differences in DNA methylation, their genetic determinants, and their respective causal impact on immune gene regulation remain elusive. Results We report extensive population differences in DNA methylation...
Humans differ in the outcome that follows exposure to life-threatening pathogens, yet the extent of population differences in immune responses and their genetic and evolutionary determinants remain undefined. Here, we characterized, using RNA sequencing, the transcriptional response of primary monocytes from Africans and Europeans to bacterial and viral stimuli—ligands activating Toll-like receptor...
Macrophages can fuse to form osteoclasts in bone or multinucleate giant cells (MGCs) as part of the immune response. We use a systems genetics approach in rat macrophages to unravel their genetic determinants of multinucleation and investigate their role in both bone homeostasis and inflammatory disease. We identify a trans-regulated gene network associated with macrophage multinucleation and Kcnn4...
Large numbers of inbred laboratory rat strains have been developed for a range of complex disease phenotypes. To gain insights into the evolutionary pressures underlying selection for these phenotypes, we sequenced the genomes of 27 rat strains, including 11 models of hypertension, diabetes, and insulin resistance, along with their respective control strains. Altogether, we identified more than 13...
In humans, the fraction of X-linked genes with higher expression in females has been estimated to be 5% from microarray studies, a proportion lower than the 25% of genes thought to escape X inactivation. We analyzed 715 X-linked transcripts in circulating monocytes from 1,467 subjects and found an excess of female-biased transcripts on the X compared to autosomes (9.4% vs 5.5%, p<2×10 −5 ...
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