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- de Rojas, I., et al.
(författare)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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| 2. |
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| 3. |
- Bellenguez, C, et al.
(författare)
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New insights into the genetic etiology of Alzheimer's disease and related dementias
- 2022
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:4, s. 412-436
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Tidskriftsartikel (refereegranskat)abstract
- Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
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| 5. |
- Martinez-Perez, A, et al.
(författare)
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Clinical Features Associated with Strongyloidiasis in Migrants and the Potential Impact of Immunosuppression: A Case Control Study
- 2020
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Ingår i: Pathogens (Basel, Switzerland). - : MDPI AG. - 2076-0817. ; 9:6
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Tidskriftsartikel (refereegranskat)abstract
- Strongyloides stercoralis is a widely distributed nematode more frequent in tropical areas and particularly severe in immunosuppressed patients. The aim of this study was to determine factors associated with strongyloidiasis in migrants living in a non-endemic area and to assess the response to treatment and follow-up in those diagnosed with the infection. We performed a multicenter case-control study with 158 cases and 294 controls matched 1:2 by a department service. Participants were recruited simultaneously at six hospitals or clinics in Spain. A paired-match analysis was then performed looking for associations and odds ratios in sociodemographic characteristics, pathological background, clinical presentation and analytical details. Cases outcomes after a six-month follow-up visit were also registered and their particularities described. Most cases and controls came from Latin America (63%–47%) or sub-Saharan Africa (26%–35%). The number of years residing in Spain (9.9 vs. 9.8, p = 0.9) and immunosuppression status (30% vs. 36.3%, p = 0.2) were also similar in both groups. Clinical symptoms such as diffuse abdominal pain (21% vs. 13%, p = 0.02), and epigastralgia (29% vs. 18%, p < 0.001); along with a higher eosinophil count (483 vs. 224 cells/mL in cases and controls, p < 0.001) and the mean total Immunoglobulin E (IgE) (354 U/L vs. 157.9 U/L; p < 0.001) were associated with having strongyloidiasis. Finally, 98.2% percent of the cases were treated with ivermectin in different schedules, and 94.5% met the cure criteria at least six months after their first consultation. Abdominal pain, epigastralgia, eosinophilia, increased levels of IgE and Latin American origin remain the main features associated with S. stercoralis infection, although this association is less evident in immunosuppressed patients. The appropriate follow-up time to evaluate treatment response based on serology titers should be extended beyond 6 months if the cure criteria are not achieved.
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| 6. |
- Requena-Mendez, A, et al.
(författare)
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High Prevalence of Strongyloidiasis in Spain: A Hospital-Based Study
- 2020
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Ingår i: Pathogens (Basel, Switzerland). - : MDPI AG. - 2076-0817. ; 9:2
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Strongyloidiasis is a prevailing helminth infection ubiquitous in tropical and subtropical areas, however, seroprevalence data are scarce in migrant populations, particularly for those coming for Asia. Methods: This study aims at evaluating the prevalence of S. stercoralis at the hospital level in migrant populations or long term travellers being attended in out-patient and in-patient units as part of a systematic screening implemented in six Spanish hospitals. A cross-sectional study was conducted and systematic screening for S. stercoralis infection using serological tests was offered to all eligible participants. Results: The overall seroprevalence of S. stercoralis was 9.04% (95%CI 7.76–10.31). The seroprevalence of people with a risk of infection acquired in Africa and Latin America was 9.35% (95%CI 7.01–11.69), 9.22% (7.5–10.93), respectively. The number of individuals coming from Asian countries was significantly smaller and the overall prevalence in these countries was 2.9% (95%CI −0.3–6.2). The seroprevalence in units attending potentially immunosuppressed patients was significantly lower (5.64%) compared with other units of the hospital (10.20%) or Tropical diseases units (13.33%) (p < 0.001). Conclusions: We report a hospital-based strongyloidiasis seroprevalence of almost 10% in a mobile population coming from endemic areas suggesting the need of implementing strongyloidiasis screening in hospitalized patients coming from endemic areas, particularly if they are at risk of immunosuppression.
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