Lorenzo Bomba

The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease

Summary Many common variants have been associated with hematological traits, but identification of causal genes and pathways has proven challenging. We performed a genome-wide association analysis in the UK Biobank and INTERVAL studies, testing 29.5 million genetic variants for association with 36 red cell, white cell, and platelet properties in 173,480 European-ancestry participants. This effort yielded hundreds of low frequency (<5%) and rare (<1%) variants with a strong impact on blood cell phenotypes. Our data highlight general properties of the allelic architecture of complex traits, including the proportion of the heritable component of each blood trait explained by the polygenic signal across different genome regulatory domains. Finally, through Mendelian randomization, we provide evidence of shared genetic pathways linking blood cell indices with complex pathologies, including autoimmune diseases, schizophrenia, and coronary heart disease and evidence suggesting previously reported population associations between blood cell indices and cardiovascular disease may be non-causal.

Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells

Summary Characterizing the multifaceted contribution of genetic and epigenetic factors to disease phenotypes is a major challenge in human genetics and medicine. We carried out high-resolution genetic, epigenetic, and transcriptomic profiling in three major human immune cell types (CD14+ monocytes, CD16+ neutrophils, and naive CD4+ T cells) from up to 197 individuals. We assess, quantitatively, the relative contribution of cis-genetic and epigenetic factors to transcription and evaluate their impact as potential sources of confounding in epigenome-wide association studies. Further, we characterize highly coordinated genetic effects on gene expression, methylation, and histone variation through quantitative trait locus (QTL) mapping and allele-specific (AS) analyses. Finally, we demonstrate colocalization of molecular trait QTLs at 345 unique immune disease loci. This expansive, high-resolution atlas of multi-omics changes yields insights into cell-type-specific correlation between diverse genomic inputs, more generalizable correlations between these inputs, and defines molecular events that may underpin complex disease risk.

The impact of rare and low-frequency genetic variants in common disease

Despite thousands of genetic loci identified to date, a large proportion of genetic variation predisposing to complex disease and traits remains unaccounted for. Advances in sequencing technology enable focused explorations on the contribution of low-frequency and rare variants to human traits. Here we review experimental approaches and current knowledge on the contribution of these genetic variants in complex disease and discuss challenges and opportunities for personalised medicine.

Oregano dietary supplementation modifies the liver transcriptome profile in broilers: RNASeq analysis

Intensive farming of broilers involves stressful conditions that reduce animal welfare and performance. New dietary strategies to improve performance and meat quality include the administration of plant extracts. Oregano (Origanum vulgare L.) is known for its antimicrobial, anti-fungal, insecticidal and antioxidant properties. However, studies on diet supplementation with oregano are mainly focused on the evaluation of animal performance, while partial information is available on transcriptomics and nutrigenomics and, in particular, Next Generation Sequencing (NGS) is not widely applied. In this study we tested the effect of an oregano aqueous extract supplemented diet on gene expression in broiler chickens. Whole liver transcriptome of 10 birds fed with a supplemented diet versus 10 controls was analyzed using the RNA-Seq technique. One hundred and twenty-nine genes were differentially expressed with an absolute log fold change >1. The analysis reveals a massive down-regulation of genes involved in fatty acid metabolism and insulin signaling pathways in broilers fed with the oregano aqueous extract supplementation. Down-regulated genes could be associated to chicken lean line, suggesting the potential beneficial effect of oregano supplementation in reducing both abdominal and visceral fat deposition. Down-regulation of insulin signaling pathway related genes suggest that dietary oregano supplementation might be an option in obesity and diabetes conditions.