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Article ; Online: Patterns of item nonresponse behaviour to survey questionnaires are systematic and associated with genetic loci.

Mignogna, Gianmarco / Carey, Caitlin E / Wedow, Robbee / Baya, Nikolas / Cordioli, Mattia / Pirastu, Nicola / Bellocco, Rino / Malerbi, Kathryn Fiuza / Nivard, Michel G / Neale, Benjamin M / Walters, Raymond K / Ganna, Andrea

Nature human behaviour

2023 Volume 7, Issue 8, Page(s) 1371–1387

Abstract: Response to survey questionnaires is vital for social and behavioural research, and most analyses assume full and accurate response by participants. However, nonresponse is common and impedes proper interpretation and generalizability of results. We ... ...

Abstract	Response to survey questionnaires is vital for social and behavioural research, and most analyses assume full and accurate response by participants. However, nonresponse is common and impedes proper interpretation and generalizability of results. We examined item nonresponse behaviour across 109 questionnaire items in the UK Biobank (N = 360,628). Phenotypic factor scores for two participant-selected nonresponse answers, 'Prefer not to answer' (PNA) and 'I don't know' (IDK), each predicted participant nonresponse in follow-up surveys (incremental pseudo-R
MeSH term(s)	Humans ; Genome-Wide Association Study ; Surveys and Questionnaires ; Self Report ; Genetic Loci
Language	English
Publishing date	2023-06-29
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2397-3374
ISSN (online)	2397-3374
DOI	10.1038/s41562-023-01632-7
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Article ; Online: Cystatin C is associated with adverse COVID-19 outcomes in diverse populations.

Kleeman, Sam O / Cordioli, Mattia / Timmers, Paul R H J / Khan, Atlas / Tober-Lau, Pinkus / Kurth, Florian / Demichev, Vadim / Meyer, Hannah V / Wilson, James F / Ralser, Markus / Kiryluk, Krzysztof / Ganna, Andrea / Baillie, Kenneth / Janowitz, Tobias

iScience

2022 Volume 25, Issue 10, Page(s) 105040

Abstract: COVID-19 has highly variable clinical courses. The search for prognostic host factors for COVID-19 outcome is a priority. We performed logistic regression for ICU admission against a polygenic score (PGS) for Cystatin C (CyC) production in patients with ... ...

Abstract	COVID-19 has highly variable clinical courses. The search for prognostic host factors for COVID-19 outcome is a priority. We performed logistic regression for ICU admission against a polygenic score (PGS) for Cystatin C (CyC) production in patients with COVID-19. We analyzed the predictive value of longitudinal plasma CyC levels in an independent cohort of patients hospitalized with COVID-19. In four cohorts spanning European and African ancestry populations, we identified a significant association between CyC-production PGS and odds of critical illness (n cases=2,319), with the strongest association captured in the UKB cohort (OR 2.13, 95% CI 1.58-2.87, p=7.12e-7). Plasma proteomics from an independent cohort of hospitalized COVID-19 patients (n cases = 131) demonstrated that CyC production was associated with COVID-specific mortality (p=0.0007). Our findings suggest that CyC may be useful for stratification of patients and it has functional role in the host response to COVID-19.
Language	English
Publishing date	2022-08-31
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2022.105040
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Article ; Online: Genetic risk factors have a substantial impact on healthy life years.

Jukarainen, Sakari / Kiiskinen, Tuomo / Kuitunen, Sara / Havulinna, Aki S / Karjalainen, Juha / Cordioli, Mattia / Rämö, Joel T / Mars, Nina / Samocha, Kaitlin E / Ollila, Hanna M / Pirinen, Matti / Ganna, Andrea

Nature medicine

2022 Volume 28, Issue 9, Page(s) 1893–1901

Abstract: The impact of genetic variation on overall disease burden has not been comprehensively evaluated. We introduce an approach to estimate the effect of genetic risk factors on disability-adjusted life years (DALYs; 'lost healthy life years'). We use genetic ...

Abstract	The impact of genetic variation on overall disease burden has not been comprehensively evaluated. We introduce an approach to estimate the effect of genetic risk factors on disability-adjusted life years (DALYs; 'lost healthy life years'). We use genetic information from 735,748 individuals and consider 80 diseases. Rare variants had the highest effect on DALYs at the individual level. Among common variants, rs3798220 (LPA) had the strongest individual-level effect, with 1.18 DALYs from carrying 1 versus 0 copies. Being in the top 10% versus the bottom 90% of a polygenic score for multisite chronic pain had an effect of 3.63 DALYs. Some common variants had a population-level effect comparable to modifiable risk factors such as high sodium intake and low physical activity. Attributable DALYs vary between males and females for some genetic exposures. Genetic risk factors can explain a sizable number of healthy life years lost both at the individual and population level.
MeSH term(s)	Female ; Global Burden of Disease ; Global Health ; Health Status ; Humans ; Male ; Quality-Adjusted Life Years ; Risk Factors ; Sodium, Dietary
Chemical Substances	Sodium, Dietary
Language	English
Publishing date	2022-09-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1220066-9
ISSN	1546-170X ; 1078-8956
ISSN (online)	1546-170X
ISSN	1078-8956
DOI	10.1038/s41591-022-01957-2
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Article ; Online: Genetic determinants of mannose-binding lectin activity predispose to thromboembolic complications in critical COVID-19.

Hultström, Michael / Frithiof, Robert / Grip, Jonathan / Lindelöf, Linnea / Rooijackers, Olav / Pigazzini, Sara / Niemi, Mari / Cordioli, Mattia / Nkambule, Lindo / Maricic, Tomislav / Ekdahl, Kristina Nilsson / Nilsson, Bo / Lipcsey, Miklós / Zeberg, Hugo / Eriksson, Oskar

Nature immunology

2022 Volume 23, Issue 6, Page(s) 861–864

MeSH term(s)	COVID-19/complications ; COVID-19/genetics ; Genotype ; Humans ; Mannose-Binding Lectins
Chemical Substances	Mannose-Binding Lectins
Language	English
Publishing date	2022-05-27
Publishing country	United States
Document type	Letter ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	2016987-5
ISSN	1529-2916 ; 1529-2908
ISSN (online)	1529-2916
ISSN	1529-2908
DOI	10.1038/s41590-022-01227-w
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Article ; Online: Genetic predictors of lifelong medication-use patterns in cardiometabolic diseases.

Kiiskinen, Tuomo / Helkkula, Pyry / Krebs, Kristi / Karjalainen, Juha / Saarentaus, Elmo / Mars, Nina / Lehisto, Arto / Zhou, Wei / Cordioli, Mattia / Jukarainen, Sakari / Rämö, Joel T / Mehtonen, Juha / Veerapen, Kumar / Räsänen, Markus / Ruotsalainen, Sanni / Maasha, Mutaamba / Niiranen, Teemu / Tuomi, Tiinamaija / Salomaa, Veikko /

Kurki, Mitja / Pirinen, Matti / Palotie, Aarno / Daly, Mark / Ganna, Andrea / Havulinna, Aki S / Milani, Lili / Ripatti, Samuli

Nature medicine

2023 Volume 29, Issue 1, Page(s) 209–218

Abstract: Little is known about the genetic determinants of medication use in preventing cardiometabolic diseases. Using the Finnish nationwide drug purchase registry with follow-up since 1995, we performed genome-wide association analyses of longitudinal patterns ...

Abstract	Little is known about the genetic determinants of medication use in preventing cardiometabolic diseases. Using the Finnish nationwide drug purchase registry with follow-up since 1995, we performed genome-wide association analyses of longitudinal patterns of medication use in hyperlipidemia, hypertension and type 2 diabetes in up to 193,933 individuals (55% women) in the FinnGen study. In meta-analyses of up to 567,671 individuals combining FinnGen with the Estonian Biobank and the UK Biobank, we discovered 333 independent loci (P < 5 × 10
MeSH term(s)	Humans ; Female ; Male ; Coronary Artery Disease/drug therapy ; Coronary Artery Disease/epidemiology ; Coronary Artery Disease/genetics ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/epidemiology ; Diabetes Mellitus, Type 2/genetics ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Risk Factors ; Cardiovascular Diseases/drug therapy ; Cardiovascular Diseases/epidemiology ; Cardiovascular Diseases/genetics
Language	English
Publishing date	2023-01-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1220066-9
ISSN	1546-170X ; 1078-8956
ISSN (online)	1546-170X
ISSN	1078-8956
DOI	10.1038/s41591-022-02122-5
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Article ; Online: Genetic Architecture of Ischaemic Strokes after COVID-19 Shows Similarities with Large Vessel Strokes.

Llucià-Carol, Laia / Muiño, Elena / Cullell, Natalia / Cárcel-Márquez, Jara / Lledós, Miquel / Gallego-Fabrega, Cristina / Martin-Campos, Jesús / Martí-Fàbregas, Joan / Aguilera-Simón, Ana / Planas, Anna M / DeDiego, Marta L / de Felipe Mimbrera, Alicia / Masjuan, Jaime / García-Madrona, Sebastián / Segura, Tomás / González-Villar, Esther / Serrano-Heras, Gemma / Domínguez Mayoral, Ana / Menéndez-Valladares, Paloma /

Montaner, Joan / Migeotte, Isabelle / Rahmouni, Souad / Darcis, Gilles / Bernardo, David / Rojo, Silvia / Schulte, Eva C / Protzer, Ulrike / Fricke, Lisa / Winter, Christof / Niemi, Mari E K / Cordioli, Mattia / Delgado, Pilar / Fernández-Cadenas, Israel

International journal of molecular sciences

2023 Volume 24, Issue 17

Abstract: We aimed to analyse whether patients with ischaemic stroke (IS) occurring within eight days after the onset of COVID-19 (IS-COV) are associated with a specific aetiology of IS. We used SUPERGNOVA to identify genome regions that correlate between the IS- ... ...

Abstract	We aimed to analyse whether patients with ischaemic stroke (IS) occurring within eight days after the onset of COVID-19 (IS-COV) are associated with a specific aetiology of IS. We used SUPERGNOVA to identify genome regions that correlate between the IS-COV cohort (73 IS-COV cases vs. 701 population controls) and different aetiological subtypes. Polygenic risk scores (PRSs) for each subtype were generated and tested in the IS-COV cohort using PRSice-2 and PLINK to find genetic associations. Both analyses used the IS-COV cohort and GWAS from MEGASTROKE (67,162 stroke patients vs. 454,450 population controls), GIGASTROKE (110,182 vs. 1,503,898), and the NINDS Stroke Genetics Network (16,851 vs. 32,473). Three genomic regions were associated (
MeSH term(s)	Humans ; Stroke/complications ; Stroke/genetics ; Brain Ischemia/complications ; Brain Ischemia/genetics ; COVID-19/complications ; COVID-19/genetics ; Ischemic Stroke/genetics ; Arteries ; Embolic Stroke ; Atherosclerosis
Language	English
Publishing date	2023-08-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241713452
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Article ; Online: Genetic analyses identify widespread sex-differential participation bias.

Pirastu, Nicola / Cordioli, Mattia / Nandakumar, Priyanka / Mignogna, Gianmarco / Abdellaoui, Abdel / Hollis, Benjamin / Kanai, Masahiro / Rajagopal, Veera M / Parolo, Pietro Della Briotta / Baya, Nikolas / Carey, Caitlin E / Karjalainen, Juha / Als, Thomas D / Van der Zee, Matthijs D / Day, Felix R / Ong, Ken K / Morisaki, Takayuki / de Geus, Eco / Bellocco, Rino /

Okada, Yukinori / Børglum, Anders D / Joshi, Peter / Auton, Adam / Hinds, David / Neale, Benjamin M / Walters, Raymond K / Nivard, Michel G / Perry, John R B / Ganna, Andrea

Nature genetics

2021 Volume 53, Issue 5, Page(s) 663–671

Abstract: Genetic association results are often interpreted with the assumption that study participation does not affect downstream analyses. Understanding the genetic basis of participation bias is challenging since it requires the genotypes of unseen individuals. ...

Abstract	Genetic association results are often interpreted with the assumption that study participation does not affect downstream analyses. Understanding the genetic basis of participation bias is challenging since it requires the genotypes of unseen individuals. Here we demonstrate that it is possible to estimate comparative biases by performing a genome-wide association study contrasting one subgroup versus another. For example, we showed that sex exhibits artifactual autosomal heritability in the presence of sex-differential participation bias. By performing a genome-wide association study of sex in approximately 3.3 million males and females, we identified over 158 autosomal loci spuriously associated with sex and highlighted complex traits underpinning differences in study participation between the sexes. For example, the body mass index-increasing allele at FTO was observed at higher frequency in males compared to females (odds ratio = 1.02, P = 4.4 × 10
MeSH term(s)	Adult ; Artifacts ; Bias ; Biological Specimen Banks ; Chromosomes, Human/genetics ; Female ; Genetic Loci ; Genome-Wide Association Study ; Humans ; Inheritance Patterns/genetics ; Male ; Polymorphism, Single Nucleotide/genetics ; Sample Size ; Sex Characteristics ; United Kingdom
Language	English
Publishing date	2021-04-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1108734-1
ISSN	1546-1718 ; 1061-4036
ISSN (online)	1546-1718
ISSN	1061-4036
DOI	10.1038/s41588-021-00846-7
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Article ; Online: Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality.

Nakanishi, Tomoko / Pigazzini, Sara / Degenhardt, Frauke / Cordioli, Mattia / Butler-Laporte, Guillaume / Maya-Miles, Douglas / Bujanda, Luis / Bouysran, Youssef / Niemi, Mari Ek / Palom, Adriana / Ellinghaus, David / Khan, Atlas / Martínez-Bueno, Manuel / Rolker, Selina / Amitrano, Sara / Roade Tato, Luisa / Fava, Francesca / Spinner, Christoph D / Prati, Daniele /

Bernardo, David / Garcia, Federico / Darcis, Gilles / Fernández-Cadenas, Israel / Holter, Jan Cato / Banales, Jesus M / Frithiof, Robert / Kiryluk, Krzysztof / Duga, Stefano / Asselta, Rosanna / Pereira, Alexandre C / Romero-Gómez, Manuel / Nafría-Jiménez, Beatriz / Hov, Johannes R / Migeotte, Isabelle / Renieri, Alessandra / Planas, Anna M / Ludwig, Kerstin U / Buti, Maria / Rahmouni, Souad / Alarcón-Riquelme, Marta E / Schulte, Eva C / Franke, Andre / Karlsen, Tom H / Valenti, Luca / Zeberg, Hugo / Richards, J Brent / Ganna, Andrea

The Journal of clinical investigation

2021 Volume 131, Issue 23

Abstract: BackgroundThere is considerable variability in COVID-19 outcomes among younger adults, and some of this variation may be due to genetic predisposition.MethodsWe combined individual level data from 13,888 COVID-19 patients (n = 7185 hospitalized) from 17 ... ...

Abstract	BackgroundThere is considerable variability in COVID-19 outcomes among younger adults, and some of this variation may be due to genetic predisposition.MethodsWe combined individual level data from 13,888 COVID-19 patients (n = 7185 hospitalized) from 17 cohorts in 9 countries to assess the association of the major common COVID-19 genetic risk factor (chromosome 3 locus tagged by rs10490770) with mortality, COVID-19-related complications, and laboratory values. We next performed metaanalyses using FinnGen and the Columbia University COVID-19 Biobank.ResultsWe found that rs10490770 risk allele carriers experienced an increased risk of all-cause mortality (HR, 1.4; 95% CI, 1.2-1.7). Risk allele carriers had increased odds of several COVID-19 complications: severe respiratory failure (OR, 2.1; 95% CI, 1.6-2.6), venous thromboembolism (OR, 1.7; 95% CI, 1.2-2.4), and hepatic injury (OR, 1.5; 95% CI, 1.2-2.0). Risk allele carriers age 60 years and younger had higher odds of death or severe respiratory failure (OR, 2.7; 95% CI, 1.8-3.9) compared with those of more than 60 years (OR, 1.5; 95% CI, 1.2-1.8; interaction, P = 0.038). Among individuals 60 years and younger who died or experienced severe respiratory failure, 32.3% were risk-variant carriers compared with 13.9% of those not experiencing these outcomes. This risk variant improved the prediction of death or severe respiratory failure similarly to, or better than, most established clinical risk factors.ConclusionsThe major common COVID-19 genetic risk factor is associated with increased risks of morbidity and mortality, which are more pronounced among individuals 60 years or younger. The effect was similar in magnitude and more common than most established clinical risk factors, suggesting potential implications for future clinical risk management.
MeSH term(s)	Age Factors ; Aged ; Aged, 80 and over ; Alleles ; COVID-19/genetics ; COVID-19/mortality ; Chromosomes, Human, Pair 3/genetics ; Female ; Gene Frequency ; Genetic Loci ; Humans ; Male ; Middle Aged ; Patient Acuity ; Polymorphism, Genetic ; Risk Factors ; SARS-CoV-2
Language	English
Publishing date	2021-09-29
Publishing country	United States
Document type	Clinical Trial ; Journal Article ; Multicenter Study ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI152386
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Article: Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality.

Nakanishi, Tomoko / Pigazzini, Sara / Degenhardt, Frauke / Cordioli, Mattia / Butler-Laporte, Guillaume / Maya-Miles, Douglas / Nafría-Jiménez, Beatriz / Bouysran, Youssef / Niemi, Mari / Palom, Adriana / Ellinghaus, David / Khan, Atlas / Martínez-Bueno, Manuel / Rolker, Selina / Amitano, Sara / Tato, Luisa Roade / Fava, Francesca / Spinner, Christoph D / Prati, Daniele /

Bernardo, David / Garcia, Federico / Darcis, Gilles / Fernández-Cadenas, Israel / Holter, Jan Cato / Banales, Jesus / Frithiof, Robert / Kiryluk, Krzysztof / Duga, Stefano / Asselta, Rosanna / Pereira, Alexandre C / Romero-Gómez, Manuel / Bujanda, Luis / Hov, Johannes R / Migeotte, Isabelle / Renieri, Alessandra / Planas, Anna M / Ludwig, Kerstin U / Buti, Maria / Rahmouni, Souad / Alarcón-Riquelme, Marta E / Schulte, Eva C / Franke, Andre / Karlsen, Tom H / Valenti, Luca / Zeberg, Hugo / Richards, J Brent / Ganna, Andrea

medRxiv : the preprint server for health sciences

2021

Abstract: Background: There is considerable variability in COVID-19 outcomes amongst younger adults-and some of this variation may be due to genetic predisposition. We characterized the clinical implications of the major genetic risk factor for COVID-19 severity, ...

Abstract	Background: There is considerable variability in COVID-19 outcomes amongst younger adults-and some of this variation may be due to genetic predisposition. We characterized the clinical implications of the major genetic risk factor for COVID-19 severity, and its age-dependent effect, using individual-level data in a large international multi-centre consortium. Method: The major common COVID-19 genetic risk factor is a chromosome 3 locus, tagged by the marker rs10490770. We combined individual level data for 13,424 COVID-19 positive patients (N=6,689 hospitalized) from 17 cohorts in nine countries to assess the association of this genetic marker with mortality, COVID-19-related complications and laboratory values. We next examined if the magnitude of these associations varied by age and were independent from known clinical COVID-19 risk factors. Findings: We found that rs10490770 risk allele carriers experienced an increased risk of all-cause mortality (hazard ratio [HR] 1·4, 95% confidence interval [CI] 1·2-1·6) and COVID-19 related mortality (HR 1·5, 95%CI 1·3-1·8). Risk allele carriers had increased odds of several COVID-19 complications: severe respiratory failure (odds ratio [OR] 2·0, 95%CI 1·6-2·6), venous thromboembolism (OR 1·7, 95%CI 1·2-2·4), and hepatic injury (OR 1·6, 95%CI 1·2-2·0). Risk allele carriers ≤ 60 years had higher odds of death or severe respiratory failure (OR 2·6, 95%CI 1·8-3·9) compared to those > 60 years OR 1·5 (95%CI 1·3-1·9, interaction p-value=0·04). Amongst individuals ≤ 60 years who died or experienced severe respiratory COVID-19 outcome, we found that 31·8% (95%CI 27·6-36·2) were risk variant carriers, compared to 13·9% (95%CI 12·6-15·2%) of those not experiencing these outcomes. Prediction of death or severe respiratory failure among those ≤ 60 years improved when including the risk allele (AUC 0·82 vs 0·84, p=0·016) and the prediction ability of rs10490770 risk allele was similar to, or better than, most established clinical risk factors. Interpretation: The major common COVID-19 risk locus on chromosome 3 is associated with increased risks of morbidity and mortality-and these are more pronounced amongst individuals ≤ 60 years. The effect on COVID-19 severity was similar to, or larger than most established risk factors, suggesting potential implications for clinical risk management. Funding: Funding was obtained by each of the participating cohorts individually.
Language	English
Publishing date	2021-03-12
Publishing country	United States
Document type	Preprint
DOI	10.1101/2021.03.07.21252875
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Article ; Online: Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality

Nakanishi, Tomoko / Pigazzini, Sara / Degenhardt, Frauke / Cordioli, Mattia / Butler-Laporte, Guillaume / Maya-Miles, Douglas / Nafr_a-Jim_nez, Beatriz / Bouysran, Youssef / Niemi, Mari / Palom, Adriana / Ellinghaus, David / Khan, Atlas / Mart_nez-Bueno, Manuel / Rolker, Selina / Amitano, Sara / Roade, Luisa / FinnGen / The COVID-19 Host Genetics Initiative / Fava, Francesca /

Spinner, Christoph D. / Prati, Daniele / Bernardo, David / Garcia, Federico / Darcis, Gilles / Fern_ndez-Cadenas, Israel / Holter, Jan Cato / Banales, Jesus / Frithiof, Robert / Kiryluk, Krzysztof / Duga, Stefano / Asselta, Rosanna / Pereira, Alexandre C. / Romero-G_mez, Manuel / Bujanda, Luis / Hov, Johannes R. / Migeotte, Isabelle / Renieri, Alessandra / Planas, Anna M. / Ludwig, Kerstin U. / Buti, Maria / Rahmouni, Souad / Alarc_n-Riquelme, Marta E. / Schulte, Eva C. / Franke, Andre / Karlsen, Tom H. / Valenti, Luca / Zeberg, Hugo / Richards, J. Brent / Ganna, Andrea

medRxiv

Abstract: Background: There is considerable variability in COVID-19 outcomes amongst younger adults and some of this variation may be due to genetic predisposition. We characterized the clinical implications of the major genetic risk factor for COVID-19 severity, ... ...

Abstract	Background: There is considerable variability in COVID-19 outcomes amongst younger adults and some of this variation may be due to genetic predisposition. We characterized the clinical implications of the major genetic risk factor for COVID-19 severity, and its age-dependent effect, using individual-level data in a large international multi-centre consortium. Method: The major common COVID-19 genetic risk factor is a chromosome 3 locus, tagged by the marker rs10490770. We combined individual level data for 13,424 COVID-19 positive patients (N=6,689 hospitalized) from 17 cohorts in nine countries to assess the association of this genetic marker with mortality, COVID-19-related complications and laboratory values. We next examined if the magnitude of these associations varied by age and were independent from known clinical COVID-19 risk factors. Findings: We found that rs10490770 risk allele carriers experienced an increased risk of all-cause mortality (hazard ratio [HR] 1.4, 95% confidence interval [CI] 1.2-1.6) and COVID-19 related mortality (HR 1.5, 95%CI 1.3-1.8). Risk allele carriers had increased odds of several COVID-19 complications: severe respiratory failure (odds ratio [OR] 2.0, 95%CI 1.6-2.6), venous thromboembolism (OR 1.7, 95%CI 1.2-2.4), and hepatic injury (OR 1.6, 95%CI 1.2-2.0). Risk allele carriers ≤ 60 years had higher odds of death or severe respiratory failure (OR 2.6, 95%CI 1.8-3.9) compared to those > 60 years OR 1.5 (95%CI 1.3-1.9, interaction p-value=0.04). Amongst individuals ≤ 60 years who died or experienced severe respiratory COVID-19 outcome, we found that 31.8% (95%CI 27.6-36.2) were risk variant carriers, compared to 13.9% (95%CI 12.6-15.2%) of those not experiencing these outcomes. Prediction of death or severe respiratory failure among those ≤ 60 years improved when including the risk allele (AUC 0.82 vs 0.84, p=0.016) and the prediction ability of rs10490770 risk allele was similar to, or better than, most established clinical risk factors. Interpretation: The major common COVID-19 risk locus on chromosome 3 is associated with increased risks of morbidity and mortality and these are more pronounced amongst individuals ≤ 60 years. The effect on COVID-19 severity was similar to, or larger than most established risk factors, suggesting potential implications for clinical risk management. Funding: Funding was obtained by each of the participating cohorts individually.
Keywords	covid19
Language	English
Publishing date	2021-03-12
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2021.03.07.21252875
Database	COVID19

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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

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Order via subito

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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

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Inter-library loan at ZB MED

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Inter-library loan at ZB MED