Kato, A. | bioRxiv Science

bioRxiv2019

Multi-omics co-localization with genome-wide association studies reveals context-specific mechanisms of asthma risk variants

BackgroundGenome-wide association studies (GWASs) have identified thousands of variants associated with asthma and other complex diseases. However, the functional effects of most of these variants are unknown. Moreover, GWASs do not provide context-specific information on cell types or environmental factors that affect specific disease risks and outcomes. To address these limitations, we used an upper airway (sinonasal) epithelial cell culture model to assess transcriptional and epigenetic responses to an asthma-promoting pathogen, rhinovirus (RV), and provide context-specific functional annotations to variants discovered in GWASs of asthma. MethodsUsing genome-wide genetic, gene expression and DNA methylation data in vehicle- and RV-treated airway epithelial cells (AECs) from 104 individuals, we mapped cis expression and methylation quantitative trait loci (cis-eQTLs and cis-meQTLs, respectively) in each condition. A Bayesian test for co-localization between AEC molecular QTLs and adult onset and childhood onset GWAS variants was used to assign function to variants associated with asthma. Mendelian randomization was applied to demonstrate DNA methylation effects on gene expression at asthma colocalized loci. ResultsCo-localization analyses of airway epithelial cell molecular QTLs with asthma GWAS variants revealed potential molecular disease mechanisms of asthma, including QTLs at the TSLP locus that were common to both exposure conditions and to both childhood and adult onset asthma, as well as QTLs at the 17q12-21 asthma locus that were specific to RV exposure and childhood onset asthma, consistent with clinical and epidemiological studies of these loci. ConclusionThis study provides information on functional effects of asthma risk variants in airway epithelial cells and insight into a disease-relevant viral exposure that modulates genetic effects on transcriptional and epigenetic responses in cells and on risk for asthma in GWASs.

genetics↗

bioRxiv2018

Sexual segregation in a highly pagophilic and sexually dimorphic marine predator

AO_SCPLOWBSTRACTC_SCPLOWSexual segregation is common in many species and has been attributed to intra-specific competition, sex-specific differences in foraging efficiency or in activity budgets and habitat choice. However, very few studies have simultaneously quantified sex-specific foraging strategies, at sea distribution, habitat use, and trophic ecology. Moreover, these studies come from low latitude areas reflecting a lack of evidence for polar species. We investigated sexual segregation in snow petrels Pagodroma nivea and combined movement, foraging trip efficiency, stable isotope and oceanographic data to test whether sexual segregation results from sex-specific habitat use. Breeding birds foraging in the Dumont dUrville sea, Antarctica, were tracked during incubation. Some similarities between males and females foraging characteristics did not support the sexual segregation hypothesis. Indeed, space-use sharing and utilization distribution, {delta}13C values and foraging trip performances (trip duration, length, speed and directions, mass gain, proportion mass gain) were similar between males and females.. However, there was support for sexual segregation in foraging characteristics linked to foraging habitats. Females foraged less than males in areas with higher sea ice concentration (SIC >70%) and had lower {delta}15N values in plasma, blood cells and feathers. Foraging efficiency (proportionate daily mass gain while foraging), was greater for females than for males, and was greater for larger females with deeper bills. Females were more efficient than males during short (<2 days) foraging trips, and for females, but not for males, mass gain, proportion mass gain and body condition at return from a foraging trip were positively correlated to SIC of the foraging areas. Together, these results suggest an absence of sexual segregation at large spatial scales in snow petrels during incubation, but strongly support habitat segregation between high (>70%) more profitable SIC (males) and low SIC areas (females), probably driven by intraspecific competition. Therefore, male and female snow petrels segregate at small spatial scales mainly determined by habitat (SIC) characteristics.

ecology↗