| 1. |
- Cruz, Raquel, et al.
(författare)
-
Novel genes and sex differences in COVID-19 severity
- 2022
-
Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 31:22, s. 3789-3806
-
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.
|
|
| 2. |
- Langefeld, Carl D., et al.
(författare)
-
Transancestral mapping and genetic load in systemic lupus erythematosus
- 2017
-
Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (similar to 50% of these regions have multiple independent associations); these include 24 novel SLE regions (P < 5 x 10(-8)), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.
|
|
| 3. |
- Aspholm-Hurtig, Marina, et al.
(författare)
-
Functional adaptation of BabA, the H. pylori ABO blood group antigen binding adhesin.
- 2004
-
Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 305:5683, s. 519-22
-
Tidskriftsartikel (refereegranskat)abstract
- Adherence by Helicobacter pylori increases the risk of gastric disease. Here, we report that more than 95% of strains that bind fucosylated blood group antigen bind A, B, and O antigens (generalists), whereas 60% of adherent South American Amerindian strains bind blood group O antigens best (specialists). This specialization coincides with the unique predominance of blood group O in these Amerindians. Strains differed about 1500-fold in binding affinities, and diversifying selection was evident in babA sequences. We propose that cycles of selection for increased and decreased bacterial adherence contribute to babA diversity and that these cycles have led to gradual replacement of generalist binding by specialist binding in blood group O-dominant human populations.
|
|
| 4. |
- Bundschuh, Jochen, et al.
(författare)
-
Emerging mitigation needs and sustainable options for solving the arsenic problems of rural and isolated urban areas in Latin America : A critical analysis
- 2010
-
Ingår i: Water Research. - : Elsevier BV. - 0043-1354 .- 1879-2448. ; 44:19, s. 5828-5845
-
Tidskriftsartikel (refereegranskat)abstract
- In this work, current information about the contamination of ground- and surface-water resources by arsenic from geogenic sources in Latin America is presented together with possible emerging mitigation solutions. The problem is of the same order of magnitude as other world regions, such as SE Asia, but it is often not described in English. Despite the studies undertaken by numerous local researchers, and the identification of proven treatment methods for the specific water conditions encountered, no technologies have been commercialized due to a current lack of funding and technical assistance. Emerging, low-cost technologies to mitigate the problem of arsenic in drinking water resources that are suitable for rural and urban areas lacking centralized water supplies have been evaluated. The technologies generally use simple and low-cost equipment that can easily be handled and maintained by the local population. Experiences comprise (i) coagulation/filtration with iron and aluminum salts, scaled-down for small community-and household-scale-applications, (ii) adsorption techniques using low-cost arsenic sorbents, such as geological materials (clays, laterites, soils, limestones), natural organic-based sorbents (natural biomass), and synthetic materials. TiO2-heterogeneous photocatalysis and zerovalent iron, especially using nanoscale particles, appear to be promising emergent technologies. Another promising innovative method for rural communities is the use of constructed wetlands using native perennial plants for arsenic rhizofiltration. Smallscale simple reverse osmosis equipment (which can be powered by wind or solar energy) that is suitable for small communities can also be utilized. The individual benefits of the different methods have been evaluated in terms of (i) size of the treatment device, (ii) arsenic concentration and distribution of species, chemical composition and grade of mineralization in the raw water, (iii) guidelines for the remaining As concentration, (iv) economical constrains, (v) complexity of installation and maintenance, and infrastructure constraints (e.g. electricity needs). (c) 2010 Elsevier Ltd. All rights reserved.
|
|
| 5. |
|
|
