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- Cruz, Raquel, et al.
(författare)
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Novel genes and sex differences in COVID-19 severity
- 2022
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 31:22, s. 3789-3806
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Tidskriftsartikel (refereegranskat)abstract
- Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.
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| 3. |
- Vicente-Santos, Amanda, et al.
(författare)
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Host-pathogen interactions under pressure : A review and meta-analysis of stress-mediated effects on disease dynamics
- 2023
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Ingår i: Ecology Letters. - 1461-023X .- 1461-0248. ; 26:11, s. 2003-2020
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Forskningsöversikt (refereegranskat)abstract
- Human activities have increased the intensity and frequency of natural stressors and created novel stressors, altering host–pathogen interactions and changing the risk of emerging infectious diseases. Despite the ubiquity of such anthropogenic impacts, predicting the directionality of outcomes has proven challenging. Here, we conduct a review and meta-analysis to determine the primary mechanisms through which stressors affect host–pathogen interactions and to evaluate the impacts stress has on host fitness (survival and fecundity) and pathogen infectivity (prevalence and intensity). We assessed 891 effect sizes from 71 host species (representing seven taxonomic groups) and 78 parasite taxa from 98 studies. We found that infected and uninfected hosts had similar sensitivity to stressors and that responses varied according to stressor type. Specifically, limited resources compromised host fecundity and decreased pathogen intensity, while abiotic environmental stressors (e.g., temperature and salinity) decreased host survivorship and increased pathogen intensity, and pollution increased mortality but decreased pathogen prevalence. We then used our meta-analysis results to develop susceptible–infected theoretical models to illustrate scenarios where infection rates are expected to increase or decrease in response to resource limitations or environmental stress gradients. Our results carry implications for conservation and disease emergence and reveal areas for future work.
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