Genetic analysis identifies molecular systems and biological pathways associated with household income, bioRxiv, 2019-03-12

AbstractSocio-economic position (SEP) is a multi-dimensional construct reflecting (and influencing) multiple socio-cultural, physical, and environmental factors. Previous genome-wide association studies (GWAS) using household income as a marker of SEP have shown that common genetic variants account for 11% of its variation. Here, in a sample of 286,301 participants from UK Biobank, we identified 30 independent genome-wide significant loci, 29 novel, that are associated with household income. Using a recently-developed method to meta-analyze data that leverages power from genetically-correlated traits, we identified an additional 120 income-associated loci. These loci showed clear evidence of functional enrichment, with transcriptional differences identified across multiple cortical tissues, in addition to links with GABAergic and serotonergic neurotransmission. We identified neurogenesis and the components of the synapse as candidate biological systems that are linked with income. By combining our GWAS on income with data from eQTL studies and chromatin interactions, 24 genes were prioritized for follow up, 18 of which were previously associated with cognitive ability. Using Mendelian Randomization, we identified cognitive ability as one of the causal, partly-heritable phenotypes that bridges the gap between molecular genetic inheritance and phenotypic consequence in terms of income differences. Significant differences between genetic correlations indicated that, the genetic variants associated with income are related to better mental health than those linked to educational attainment (another commonly-used marker of SEP). Finally, we were able to predict 2.5% of income differences using genetic data alone in an independent sample. These results are important for understanding the observed socioeconomic inequalities in Great Britain today.

biorxiv genetics 200-500-users 2019

Convergent gene loss in aquatic plants predicts new components of plant immunity and drought response, bioRxiv, 2019-03-11

AbstractThe transition of plants from sea to land sparked an arms race with pathogens. The increased susceptibility of land plants is largely thought to be due to their dependence on micro-organisms for nutrients; the ensuing co-evolution has shaped the plant immune system. By profiling the immune receptors across flowering plants, we identified species with low numbers of NLR immune receptors. Interestingly, four of these species represent distinct lineages of monocots and dicots that returned to the aquatic lifestyle. Both aquatic monocot and dicot species lost the same well-known downstream immune signalling complex (EDS1-PAD4). This observation inspired us to look for other genes with a similar loss pattern and allowed us to predict putative new components of plant immunity. Gene expression analyses confirmed that a group of these genes was differentially expressed under pathogen infection. Excitingly, another subset of these genes was differentially expressed upon drought. Collectively, our study reveals the minimal plant immune system required for life under water, and highlights additional components required for the life of land plants.Author summaryPlant resistance to pathogens is commonly mediated by a complex gene family, known as NLRs. Upon pathogen infection, changes in the cellular environment trigger NLR activation and subsequent defence responses. Despite the dependence of agricultural practices on NLR genes to control pathogen load, relatively little is known about this gene family outside of model crop species. In this study, we identified a convergent reduction in the NLR gene family among two lineages of aquatic plants. Furthermore, we established that NLR reduction occurred in conjunction with the loss of a common immune signalling pathway. Subsequently, we identified other genes convergently lost in aquatic species and propose these as candidate components of the plant immune signalling pathway. In addition, we revealed components of the agronomically important drought response to be lost in aquatic plants. This study adds to our understanding of the complex interactions between environment and response to biotic stress, widely known as the disease triangle. The pathways identified in this study shed further light on the link between responses to drought and disease.

biorxiv plant-biology 100-200-users 2019

 

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