Marit Mæhle Grimsrud

• Steiert, Tim A.; Parra, Genís; Gut, Marta; Arnold, Norbert; Trotta, Jean-Rémi & Tonda, Raúl [Show all 23 contributors for this article] (2023). A critical spotlight on the paradigms of FFPE-DNA sequencing. Nucleic Acids Research (NAR). ISSN 0305-1048. 51(14), p. 7143–7162. doi: 10.1093/nar/gkad519. Full text in Research Archive
• Lapitz, Ainhoa; Azkargorta, Mikel; Milkiewicz, Piotr; Olaizola, Paula; Zhuravleva, Ekaterina & Grimsrud, Marit Mæhle [Show all 35 contributors for this article] (2023). Liquid biopsy-based protein biomarkers for risk prediction, early diagnosis, and prognostication of cholangiocarcinoma. Journal of Hepatology. ISSN 0168-8278. 79(1), p. 93–108. doi: 10.1016/j.jhep.2023.02.027. Full text in Research Archive
• Degenhardt, Frauke; Ellinghaus, David; Juzenas, Simonas; Lerga-Jaso, Jon; Wendorff, Mareike & Maya-Miles, Douglas [Show all 51 contributors for this article] (2022). Detailed stratified GWAS analysis for severe COVID-19 in four European populations. Human Molecular Genetics. ISSN 0964-6906. 31(23), p. 3945–3966. doi: 10.1093/hmg/ddac158. Full text in Research Archive Show summary

  Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended genome-wide association meta-analysis of a well-characterized cohort of 3255 COVID-19 patients with respiratory failure and 12 488 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.31 to a ∼0.9-Mb inversion polymorphism that creates two highly differentiated haplotypes and characterized the potential effects of the inversion in detail. Our data, together with the 5th release of summary statistics from the COVID-19 Host Genetics Initiative including non-Caucasian individuals, also identified a new locus at 19q13.33, including NAPSA, a gene which is expressed primarily in alveolar cells responsible for gas exchange in the lung.

• Hammer, Quirin; Dunst, Josefine; Christ, Wanda; Picarazzi, Francesca; Wendorff, Mareike & Momayyezi, Pouria [Show all 51 contributors for this article] (2022). SARS-CoV-2 Nsp13 encodes for an HLA-E-stabilizing peptide that abrogates inhibition of NKG2A-expressing NK cells. Cell reports. ISSN 2211-1247. 38(10). doi: 10.1016/j.celrep.2022.110503. Full text in Research Archive Show summary

  Natural killer (NK) cells are innate immune cells that contribute to host defense against virus infections. NK cells respond to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro and are activated in patients with acute coronavirus disease 2019 (COVID-19). However, by which mechanisms NK cells detect SARS-CoV-2-infected cells remains largely unknown. Here, we show that the Non-structural protein 13 of SARS-CoV-2 encodes for a peptide that is presented by human leukocyte antigen E (HLA-E). In contrast with self-peptides, the viral peptide prevents binding of HLA-E to the inhibitory receptor NKG2A, thereby rendering target cells susceptible to NK cell attack. In line with these observations, NKG2A-expressing NK cells are particularly activated in patients with COVID-19 and proficiently limit SARS-CoV-2 replication in infected lung epithelial cells in vitro. Thus, these data suggest that a viral peptide presented by HLA-E abrogates inhibition of NKG2A+ NK cells, resulting in missing self-recognition.

• Vedeld, Hege Marie; Grimsrud, Marit Mæhle; Andresen, Kim; Pharo, Heidi Dietrichson; von Seth, Erik & Karlsen, Tom Hemming [Show all 15 contributors for this article] (2021). Early and accurate detection of cholangiocarcinoma in patients with primary sclerosing cholangitis by methylation markers in bile. Hepatology. ISSN 0270-9139. doi: 10.1002/hep.32125. Full text in Research Archive
• Niemi, Mari E.K.; Karjalainen, Juha; Liao, Rachel G.; Neale, Benjamin M.; Daly, Mark & Ganna, Andrea [Show all 84 contributors for this article] (2021). Mapping the human genetic architecture of COVID-19. Nature. ISSN 0028-0836. 600(7889), p. 472–477. doi: 10.1038/s41586-021-03767-x. Full text in Research Archive Show summary

  The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3,4,5,6,7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.

• Ellinghaus, David; Degenhardt, Frauke; Bujanda, Luis; Buti, Maria; Abillios, Agustin & Invernizzi, Pietro [Show all 30 contributors for this article] (2020). Genomewide Association Study of Severe Covid-19 with Respiratory Failure. New England Journal of Medicine. ISSN 0028-4793. doi: 10.1056/NEJMoa2020283.
• Goeppert, Benjamin; Folseraas, Trine; Roessler, Stephanie; Kloor, Matthias; Volckmar, Anna-Lena & Endris, Volker [Show all 36 contributors for this article] (2020). Genomic characterization of cholangiocarcinoma in primary sclerosing cholangitis reveals therapeutic opportunities. Hepatology. ISSN 0270-9139. 72(4), p. 1253–1266. doi: 10.1002/hep.31110. Full text in Research Archive
• Grimsrud, Marit Mæhle & Folseraas, Trine (2019). Pathogenesis, diagnosis and treatment of premalignant and malignant stages of cholangiocarcinoma in primary sclerosing cholangitis. Liver international (Print). ISSN 1478-3223. p. 1–8. doi: 10.1111/liv.14180. Full text in Research Archive
• Grimsrud, Marit Mæhle; Brekke, Mette; Syse, Victoria Lykke & Vallersnes, Odd Martin (2019). Acute poisoning related to the recreational use of prescription drugs: an observational study from Oslo, Norway. BMC Emergency Medicine. ISSN 1471-227X. 19. doi: 10.1186/s12873-019-0271-0. Full text in Research Archive
• Syse, Victoria Lykke; Brekke, Mette; Grimsrud, Marit Mæhle; Persett, Per Sverre; Heyerdahl, Fridtjof & Hovda, Knut Erik [Show all 7 contributors for this article] (2019). Gender differences in acute recreational drug toxicity: a case series from Oslo, Norway. BMC Emergency Medicine. ISSN 1471-227X. 19(1). doi: 10.1186/s12873-019-0244-3. Full text in Research Archive Show summary

  Background Female drug users report poorer physical and mental health than male drug users. We describe female and male patients treated for acute recreational drug toxicity, and look for gender differences in clinical state, treatment, and toxic agents taken. Methods Retrospective case series from a primary care emergency outpatient clinic and a hospital emergency department in Oslo, Norway. All patients treated for acute recreational drug toxicity from October 2013 through March 2015 were included, except patients with lone alcohol intoxication. Patients were grouped according to whether they had taken opioids or not, as a proxy differentiation between heavy drug users and party drug users. Data from the two clinical settings were analysed separately. Results In total, 2495 cases were included, 567 (22.7%) were women. Female patients were younger than males, median 31 vs 34 years (p < 0.001). On most comparisons of clinical variables there were no significant differences between genders. A larger proportion of females in the outpatient opioid group were hypotensive, 10.9% vs 3.9% (p < 0.001). Fewer females were intubated, none vs 21.1% (p = 0.019) in the hospital opioid group, and 6.4% vs 21.0% (p = 0.039) in the hospital non-opioid group. The proportion of gamma-hydroxybutyrate (GHB) poisoning was larger among females both at the outpatient clinic (14.4% vs 8.6%, p < 0.001) and at the hospital (60.3% vs 36.4%, p = 0.001), while the proportion of heroin poisoning was smaller among females at the outpatient clinic (37.1% vs 47.0%, p < 0.001). Conclusion One in four patients treated for acute recreational drug toxicity were women. Female patients were younger, had more frequently taken GHB and were less frequently intubated. Otherwise, the gender differences regarding clinical state and treatment were small. Although female drug users are known to report poorer health than males, we did not find that women had a more severe clinical course than men when presenting with overdose.

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• Grimsrud, Marit Mæhle; Brekke, Mette; Syse, Victoria Lykke & Vallersnes, Odd Martin (2019). Acute poisoning related to recreational use of prescription drugs.
• Syse, Victoria Lykke; Brekke, Mette; Grimsrud, Marit Mæhle; Persett, Per Sverre; Heyerdahl, Fridtjof & Hovda, Knut Erik [Show all 7 contributors for this article] (2019). Acute recreational drug toxicity in women: a case series from Oslo, Norway.

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