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Artikel ; Online: Lack of association between genetic variants at ACE2 and TMPRSS2 genes involved in SARS-CoV-2 infection and human quantitative phenotypes

Esteban Lopera / Adriaan van der Graaf / Pauline Lanting / Marije van der Geest / Jingyuan Fu / Morris Swertz / Lude Franke / Cisca Wijmenga / Patrick Deelen / Alexandra Zhernakova / Serena Sanna

Abstract: Coronavirus disease 2019 (COVID-19) shows a wide variation in expression and severity of symptoms, from very mild or no symptomes, to flu-like symptoms, and in more severe cases, to pneumonia, acute respiratory distress syndrome and even death. Large ... ...

Abstract	Coronavirus disease 2019 (COVID-19) shows a wide variation in expression and severity of symptoms, from very mild or no symptomes, to flu-like symptoms, and in more severe cases, to pneumonia, acute respiratory distress syndrome and even death. Large differences in outcome have also been observed between males and females. The causes for this variability are likely to be multifactorial, and to include genetics. The SARS-CoV-2 virus responsible for the infection uses the human receptor angiotensin converting enzyme 2 (ACE2) for cell invasion, and the serine protease TMPRSS2 for S protein priming. Genetic variation in these two genes may thus modulate an individual's genetic predisposition to infection and virus clearance. While genetic data on COVID-19 patients is being gathered, we carried out a phenome-wide association scan (PheWAS) to investigate the role of these genes in other human phenotypes in the general population. We examined 178 quantitative phenotypes including cytokines and cardio-metabolic biomarkers, as well as 58 medications in 36,339 volunteers from the Lifelines population biobank, in relation to 1,273 genetic variants located in or near ACE2 and TMPRSS2. While none reached our threshold for significance, we observed a suggestive association of polymorphisms within the ACE2 gene with (1) the use of ARBs combination therapies (p=5.7x10-4), an association that is significantly stronger in females (pdiff=0.01), and (2) with the use of non-steroid anti-inflammatory and antirheumatic products (p=5.5x10-4). While these associations need to be confirmed in larger sample sizes, they suggest that these variants play a role in diseases such as hypertension and chronic inflammation that are often observed in the more severe COVID-19 cases. Further investigation of these genetic variants in the context of COVID-19 is thus promising for better understanding of disease variability. Full results are available at https://covid19research.nl.
Schlagwörter	covid19
Verlag	medrxiv
Dokumenttyp	Artikel ; Online
DOI	10.1101/2020.04.22.20074963
Datenquelle	COVID19

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Artikel ; Online: Lack of Association Between Genetic Variants at ACE2 and TMPRSS2 Genes Involved in SARS-CoV-2 Infection and Human Quantitative Phenotypes

Esteban A. Lopera Maya / Adriaan van der Graaf / Pauline Lanting / Marije van der Geest / Jingyuan Fu / Morris Swertz / Lude Franke / Cisca Wijmenga / Patrick Deelen / Alexandra Zhernakova / Serena Sanna / Lifelines Cohort Study

Frontiers in Genetics, Vol

2020 Band 11

Abstract: Coronavirus disease 2019 (COVID-19) shows a wide variation in expression and severity of symptoms, from very mild or no symptoms, to flu-like symptoms, and in more severe cases, to pneumonia, acute respiratory distress syndrome, and even death. Large ... ...

Abstract	Coronavirus disease 2019 (COVID-19) shows a wide variation in expression and severity of symptoms, from very mild or no symptoms, to flu-like symptoms, and in more severe cases, to pneumonia, acute respiratory distress syndrome, and even death. Large differences in outcome have also been observed between males and females. The causes for this variability are likely to be multifactorial, and to include genetics. The SARS-CoV-2 virus responsible for the infection depends on two human genes: the human receptor angiotensin converting enzyme 2 (ACE2) for cell invasion, and the serine protease TMPRSS2 for S protein priming. Genetic variation in these two genes may thus modulate an individual's genetic predisposition to infection and virus clearance. While genetic data on COVID-19 patients is being gathered, we carried out a phenome-wide association scan (PheWAS) to investigate the role of these genes in other human phenotypes in the general population. We examined 178 quantitative phenotypes including cytokines and cardio-metabolic biomarkers, as well as usage of 58 medications in 36,339 volunteers from the Lifelines population cohort, in relation to 1,273 genetic variants located in or near ACE2 and TMPRSS2. While none reached our threshold for significance, we observed several interesting suggestive associations. For example, single nucleotide polymorphisms (SNPs) near the TMPRSS2 genes were associated with thrombocytes count (p = 1.8 × 10−5). SNPs within the ACE2 gene were associated with (1) the use of angiotensin II receptor blockers (ARBs) combination therapies (p = 5.7 × 10−4), an association that is significantly stronger in females (pdiff = 0.01), and (2) with the use of non-steroid anti-inflammatory and antirheumatic products (p = 5.5 × 10−4). While these associations need to be confirmed in larger sample sizes, they suggest that these variants could play a role in diseases such as thrombocytopenia, hypertension, and chronic inflammation that are often observed in the more severe COVID-19 cases. Further investigation of these genetic variants in the context of COVID-19 is thus promising for better understanding of disease variability. Full results are available at https://covid19research.nl.
Schlagwörter	PheWAS ; ACE2 ; TMPRSS2 ; NSAIDs (non-steroidal anti-inflammatory drugs) ; ARBs (angiotensin II receptor blockers) ; COVID-19 ; Genetics ; QH426-470 ; covid19
Thema/Rubrik (Code)	616
Sprache	Englisch
Erscheinungsdatum	2020-06-01T00:00:00Z
Verlag	Frontiers Media S.A.
Dokumenttyp	Artikel ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Buch ; Online: Table_2_Lack of Association Between Genetic Variants at ACE2 and TMPRSS2 Genes Involved in SARS-CoV-2 Infection and Human Quantitative Phenotypes.XLSX

2020

Abstract	Coronavirus disease 2019 (COVID-19) shows a wide variation in expression and severity of symptoms, from very mild or no symptoms, to flu-like symptoms, and in more severe cases, to pneumonia, acute respiratory distress syndrome, and even death. Large differences in outcome have also been observed between males and females. The causes for this variability are likely to be multifactorial, and to include genetics. The SARS-CoV-2 virus responsible for the infection depends on two human genes: the human receptor angiotensin converting enzyme 2 (ACE2) for cell invasion, and the serine protease TMPRSS2 for S protein priming. Genetic variation in these two genes may thus modulate an individual's genetic predisposition to infection and virus clearance. While genetic data on COVID-19 patients is being gathered, we carried out a phenome-wide association scan (PheWAS) to investigate the role of these genes in other human phenotypes in the general population. We examined 178 quantitative phenotypes including cytokines and cardio-metabolic biomarkers, as well as usage of 58 medications in 36,339 volunteers from the Lifelines population cohort, in relation to 1,273 genetic variants located in or near ACE2 and TMPRSS2. While none reached our threshold for significance, we observed several interesting suggestive associations. For example, single nucleotide polymorphisms (SNPs) near the TMPRSS2 genes were associated with thrombocytes count (p = 1.8 × 10 −5 ). SNPs within the ACE2 gene were associated with (1) the use of angiotensin II receptor blockers (ARBs) combination therapies (p = 5.7 × 10 −4 ), an association that is significantly stronger in females (p dif f = 0.01), and (2) with the use of non-steroid anti-inflammatory and antirheumatic products (p = 5.5 × 10 −4 ). While these associations need to be confirmed in larger sample sizes, they suggest that these variants could play a role in diseases such as thrombocytopenia, hypertension, and chronic inflammation that are often observed in the more severe COVID-19 cases. Further investigation of these genetic variants in the context of COVID-19 is thus promising for better understanding of disease variability. Full results are available at https://covid19research.nl.
Schlagwörter	Genetics ; Genetic Engineering ; Biomarkers ; Developmental Genetics (incl. Sex Determination) ; Epigenetics (incl. Genome Methylation and Epigenomics) ; Gene Expression (incl. Microarray and other genome-wide approaches) ; Genome Structure and Regulation ; Genomics ; Genetically Modified Animals ; Livestock Cloning ; Gene and Molecular Therapy ; PheWAS ; ACE2 ; TMPRSS2 ; NSAIDs (non-steroidal anti-inflammatory drugs) ; ARBs (angiotensin II receptor blockers) ; COVID-19 ; SARS-CoV-2 ; covid19
Thema/Rubrik (Code)	572
Erscheinungsdatum	2020-06-08T14:39:08Z
Erscheinungsland	uk
Dokumenttyp	Buch ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Buch ; Online: Table_3_Lack of Association Between Genetic Variants at ACE2 and TMPRSS2 Genes Involved in SARS-CoV-2 Infection and Human Quantitative Phenotypes.XLSX

2020

Abstract	Coronavirus disease 2019 (COVID-19) shows a wide variation in expression and severity of symptoms, from very mild or no symptoms, to flu-like symptoms, and in more severe cases, to pneumonia, acute respiratory distress syndrome, and even death. Large differences in outcome have also been observed between males and females. The causes for this variability are likely to be multifactorial, and to include genetics. The SARS-CoV-2 virus responsible for the infection depends on two human genes: the human receptor angiotensin converting enzyme 2 (ACE2) for cell invasion, and the serine protease TMPRSS2 for S protein priming. Genetic variation in these two genes may thus modulate an individual's genetic predisposition to infection and virus clearance. While genetic data on COVID-19 patients is being gathered, we carried out a phenome-wide association scan (PheWAS) to investigate the role of these genes in other human phenotypes in the general population. We examined 178 quantitative phenotypes including cytokines and cardio-metabolic biomarkers, as well as usage of 58 medications in 36,339 volunteers from the Lifelines population cohort, in relation to 1,273 genetic variants located in or near ACE2 and TMPRSS2. While none reached our threshold for significance, we observed several interesting suggestive associations. For example, single nucleotide polymorphisms (SNPs) near the TMPRSS2 genes were associated with thrombocytes count (p = 1.8 × 10 −5 ). SNPs within the ACE2 gene were associated with (1) the use of angiotensin II receptor blockers (ARBs) combination therapies (p = 5.7 × 10 −4 ), an association that is significantly stronger in females (p dif f = 0.01), and (2) with the use of non-steroid anti-inflammatory and antirheumatic products (p = 5.5 × 10 −4 ). While these associations need to be confirmed in larger sample sizes, they suggest that these variants could play a role in diseases such as thrombocytopenia, hypertension, and chronic inflammation that are often observed in the more severe COVID-19 cases. Further investigation of these genetic variants in the context of COVID-19 is thus promising for better understanding of disease variability. Full results are available at https://covid19research.nl.
Schlagwörter	Genetics ; Genetic Engineering ; Biomarkers ; Developmental Genetics (incl. Sex Determination) ; Epigenetics (incl. Genome Methylation and Epigenomics) ; Gene Expression (incl. Microarray and other genome-wide approaches) ; Genome Structure and Regulation ; Genomics ; Genetically Modified Animals ; Livestock Cloning ; Gene and Molecular Therapy ; PheWAS ; ACE2 ; TMPRSS2 ; NSAIDs (non-steroidal anti-inflammatory drugs) ; ARBs (angiotensin II receptor blockers) ; COVID-19 ; SARS-CoV-2 ; covid19
Thema/Rubrik (Code)	572
Erscheinungsdatum	2020-06-08T14:39:08Z
Erscheinungsland	uk
Dokumenttyp	Buch ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Audio / Video ; Online: Image_1_Lack of Association Between Genetic Variants at ACE2 and TMPRSS2 Genes Involved in SARS-CoV-2 Infection and Human Quantitative Phenotypes.jpg

2020

Abstract	Coronavirus disease 2019 (COVID-19) shows a wide variation in expression and severity of symptoms, from very mild or no symptoms, to flu-like symptoms, and in more severe cases, to pneumonia, acute respiratory distress syndrome, and even death. Large differences in outcome have also been observed between males and females. The causes for this variability are likely to be multifactorial, and to include genetics. The SARS-CoV-2 virus responsible for the infection depends on two human genes: the human receptor angiotensin converting enzyme 2 (ACE2) for cell invasion, and the serine protease TMPRSS2 for S protein priming. Genetic variation in these two genes may thus modulate an individual's genetic predisposition to infection and virus clearance. While genetic data on COVID-19 patients is being gathered, we carried out a phenome-wide association scan (PheWAS) to investigate the role of these genes in other human phenotypes in the general population. We examined 178 quantitative phenotypes including cytokines and cardio-metabolic biomarkers, as well as usage of 58 medications in 36,339 volunteers from the Lifelines population cohort, in relation to 1,273 genetic variants located in or near ACE2 and TMPRSS2. While none reached our threshold for significance, we observed several interesting suggestive associations. For example, single nucleotide polymorphisms (SNPs) near the TMPRSS2 genes were associated with thrombocytes count (p = 1.8 × 10 −5 ). SNPs within the ACE2 gene were associated with (1) the use of angiotensin II receptor blockers (ARBs) combination therapies (p = 5.7 × 10 −4 ), an association that is significantly stronger in females (p dif f = 0.01), and (2) with the use of non-steroid anti-inflammatory and antirheumatic products (p = 5.5 × 10 −4 ). While these associations need to be confirmed in larger sample sizes, they suggest that these variants could play a role in diseases such as thrombocytopenia, hypertension, and chronic inflammation that are often observed in the more severe COVID-19 cases. Further investigation of these genetic variants in the context of COVID-19 is thus promising for better understanding of disease variability. Full results are available at https://covid19research.nl.
Schlagwörter	Genetics ; Genetic Engineering ; Biomarkers ; Developmental Genetics (incl. Sex Determination) ; Epigenetics (incl. Genome Methylation and Epigenomics) ; Gene Expression (incl. Microarray and other genome-wide approaches) ; Genome Structure and Regulation ; Genomics ; Genetically Modified Animals ; Livestock Cloning ; Gene and Molecular Therapy ; PheWAS ; ACE2 ; TMPRSS2 ; NSAIDs (non-steroidal anti-inflammatory drugs) ; ARBs (angiotensin II receptor blockers) ; COVID-19 ; SARS-CoV-2 ; covid19
Thema/Rubrik (Code)	572
Erscheinungsdatum	2020-06-08T14:39:07Z
Erscheinungsland	uk
Dokumenttyp	Audio / Video ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Buch ; Online: Table_1_Lack of Association Between Genetic Variants at ACE2 and TMPRSS2 Genes Involved in SARS-CoV-2 Infection and Human Quantitative Phenotypes.XLSX

2020

Abstract	Coronavirus disease 2019 (COVID-19) shows a wide variation in expression and severity of symptoms, from very mild or no symptoms, to flu-like symptoms, and in more severe cases, to pneumonia, acute respiratory distress syndrome, and even death. Large differences in outcome have also been observed between males and females. The causes for this variability are likely to be multifactorial, and to include genetics. The SARS-CoV-2 virus responsible for the infection depends on two human genes: the human receptor angiotensin converting enzyme 2 (ACE2) for cell invasion, and the serine protease TMPRSS2 for S protein priming. Genetic variation in these two genes may thus modulate an individual's genetic predisposition to infection and virus clearance. While genetic data on COVID-19 patients is being gathered, we carried out a phenome-wide association scan (PheWAS) to investigate the role of these genes in other human phenotypes in the general population. We examined 178 quantitative phenotypes including cytokines and cardio-metabolic biomarkers, as well as usage of 58 medications in 36,339 volunteers from the Lifelines population cohort, in relation to 1,273 genetic variants located in or near ACE2 and TMPRSS2. While none reached our threshold for significance, we observed several interesting suggestive associations. For example, single nucleotide polymorphisms (SNPs) near the TMPRSS2 genes were associated with thrombocytes count (p = 1.8 × 10 −5 ). SNPs within the ACE2 gene were associated with (1) the use of angiotensin II receptor blockers (ARBs) combination therapies (p = 5.7 × 10 −4 ), an association that is significantly stronger in females (p dif f = 0.01), and (2) with the use of non-steroid anti-inflammatory and antirheumatic products (p = 5.5 × 10 −4 ). While these associations need to be confirmed in larger sample sizes, they suggest that these variants could play a role in diseases such as thrombocytopenia, hypertension, and chronic inflammation that are often observed in the more severe COVID-19 cases. Further investigation of these genetic variants in the context of COVID-19 is thus promising for better understanding of disease variability. Full results are available at https://covid19research.nl.
Schlagwörter	Genetics ; Genetic Engineering ; Biomarkers ; Developmental Genetics (incl. Sex Determination) ; Epigenetics (incl. Genome Methylation and Epigenomics) ; Gene Expression (incl. Microarray and other genome-wide approaches) ; Genome Structure and Regulation ; Genomics ; Genetically Modified Animals ; Livestock Cloning ; Gene and Molecular Therapy ; PheWAS ; ACE2 ; TMPRSS2 ; NSAIDs (non-steroidal anti-inflammatory drugs) ; ARBs (angiotensin II receptor blockers) ; COVID-19 ; SARS-CoV-2 ; covid19
Thema/Rubrik (Code)	572
Erscheinungsdatum	2020-06-08T14:39:07Z
Erscheinungsland	uk
Dokumenttyp	Buch ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Buch ; Online: Table_4_Lack of Association Between Genetic Variants at ACE2 and TMPRSS2 Genes Involved in SARS-CoV-2 Infection and Human Quantitative Phenotypes.xlsx

2020

Abstract	Coronavirus disease 2019 (COVID-19) shows a wide variation in expression and severity of symptoms, from very mild or no symptoms, to flu-like symptoms, and in more severe cases, to pneumonia, acute respiratory distress syndrome, and even death. Large differences in outcome have also been observed between males and females. The causes for this variability are likely to be multifactorial, and to include genetics. The SARS-CoV-2 virus responsible for the infection depends on two human genes: the human receptor angiotensin converting enzyme 2 (ACE2) for cell invasion, and the serine protease TMPRSS2 for S protein priming. Genetic variation in these two genes may thus modulate an individual's genetic predisposition to infection and virus clearance. While genetic data on COVID-19 patients is being gathered, we carried out a phenome-wide association scan (PheWAS) to investigate the role of these genes in other human phenotypes in the general population. We examined 178 quantitative phenotypes including cytokines and cardio-metabolic biomarkers, as well as usage of 58 medications in 36,339 volunteers from the Lifelines population cohort, in relation to 1,273 genetic variants located in or near ACE2 and TMPRSS2. While none reached our threshold for significance, we observed several interesting suggestive associations. For example, single nucleotide polymorphisms (SNPs) near the TMPRSS2 genes were associated with thrombocytes count (p = 1.8 × 10 −5 ). SNPs within the ACE2 gene were associated with (1) the use of angiotensin II receptor blockers (ARBs) combination therapies (p = 5.7 × 10 −4 ), an association that is significantly stronger in females (p dif f = 0.01), and (2) with the use of non-steroid anti-inflammatory and antirheumatic products (p = 5.5 × 10 −4 ). While these associations need to be confirmed in larger sample sizes, they suggest that these variants could play a role in diseases such as thrombocytopenia, hypertension, and chronic inflammation that are often observed in the more severe COVID-19 cases. Further investigation of these genetic variants in the context of COVID-19 is thus promising for better understanding of disease variability. Full results are available at https://covid19research.nl.
Schlagwörter	Genetics ; Genetic Engineering ; Biomarkers ; Developmental Genetics (incl. Sex Determination) ; Epigenetics (incl. Genome Methylation and Epigenomics) ; Gene Expression (incl. Microarray and other genome-wide approaches) ; Genome Structure and Regulation ; Genomics ; Genetically Modified Animals ; Livestock Cloning ; Gene and Molecular Therapy ; PheWAS ; ACE2 ; TMPRSS2 ; NSAIDs (non-steroidal anti-inflammatory drugs) ; ARBs (angiotensin II receptor blockers) ; COVID-19 ; SARS-CoV-2 ; covid19
Thema/Rubrik (Code)	572
Erscheinungsdatum	2020-06-08T14:39:08Z
Erscheinungsland	uk
Dokumenttyp	Buch ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Artikel ; Online: Comprehensive evaluation of smoking exposures and their interactions on DNA methylationResearch in context

Thanh T. Hoang / Yunsung Lee / Daniel L. McCartney / Elin T.G. Kersten / Christian M. Page / Paige M. Hulls / Mikyeong Lee / Rosie M. Walker / Charles E. Breeze / Brian D. Bennett / Adam B. Burkholder / James Ward / Anne Lise Brantsæter / Ida H. Caspersen / Alison A. Motsinger-Reif / Marie Richards / Julie D. White / Shanshan Zhao / Rebecca C. Richmond /

Maria C. Magnus / Gerard H. Koppelman / Kathryn L. Evans / Riccardo E. Marioni / Siri E. Håberg / Stephanie J. London / Bastiaan Heijmans / Peter ’t Hoen / Joyce van Meurs / Rick Jansen / Lude Franke / Dorret Boomsma / René Pool / Jenny van Dongen / Jouke Hottenga / Marleen van Greevenbroek / Coen Stehouwer / Carla van der Kallen / Casper Schalkwijk / Cisca Wijmenga / Sasha Zhernakova / Ettje Tigchelaar / P. Eline Slagboom / Marian Beekman / Joris Deelen / Diana Van Heemst / Jan Veldink / Leonard van den Berg / Cornelia van Duijn / Bert Hofman / Aaron Isaacs / André Uitterlinden / P. Mila Jhamai / Michael Verbiest / H. Eka Suchiman / Marijn Verkerk / Ruud van der Breggen / Jeroen van Rooij / Nico Lakenberg / Hailiang Mei / Maarten van Iterson / Michiel van Galen / Jan Bot / Dasha Zhernakova / Peter van ‘t Hof / Patrick Deelen / Irene Nooren / Matthijs Moed / Martijn Vermaat / René Luijk / Marc Bonder / Freerk van Dijk / Wibowo Arindrarto / Szymon Kielbasa / Morris Swertz / Erik van Zwet

EBioMedicine, Vol 100, Iss , Pp 104956- (2024)

2024

Abstract: Summary: Background: Smoking impacts DNA methylation, but data are lacking on smoking-related differential methylation by sex or dietary intake, recent smoking cessation (<1 year), persistence of differential methylation from in utero smoking exposure, ... ...

Abstract	Summary: Background: Smoking impacts DNA methylation, but data are lacking on smoking-related differential methylation by sex or dietary intake, recent smoking cessation (<1 year), persistence of differential methylation from in utero smoking exposure, and effects of environmental tobacco smoke (ETS). Methods: We meta-analysed data from up to 15,014 adults across 5 cohorts with DNA methylation measured in blood using Illumina's EPIC array for current smoking (2560 exposed), quit < 1 year (500 exposed), in utero (286 exposed), and ETS exposure (676 exposed). We also evaluated the interaction of current smoking with sex or diet (fibre, folate, and vitamin C). Findings: Using false discovery rate (FDR < 0.05), 65,857 CpGs were differentially methylated in relation to current smoking, 4025 with recent quitting, 594 with in utero exposure, and 6 with ETS. Most current smoking CpGs attenuated within a year of quitting. CpGs related to in utero exposure in adults were enriched for those previously observed in newborns. Differential methylation by current smoking at 4–71 CpGs may be modified by sex or dietary intake. Nearly half (35–50%) of differentially methylated CpGs on the 450 K array were associated with blood gene expression. Current smoking and in utero smoking CpGs implicated 3049 and 1067 druggable targets, including chemotherapy drugs. Interpretation: Many smoking-related methylation sites were identified with Illumina’s EPIC array. Most signals revert to levels observed in never smokers within a year of cessation. Many in utero smoking CpGs persist into adulthood. Smoking-related druggable targets may provide insights into cancer treatment response and shared mechanisms across smoking-related diseases. Funding: Intramural Research Program of the National Institutes of Health, Norwegian Ministry of Health and Care Services and the Ministry of Education and Research, Chief Scientist Office of the Scottish Government Health Directorates and the Scottish Funding Council, Medical Research Council UK and ...
Schlagwörter	Illumina EPIC array ; Epigenomics ; Secondhand smoke exposure ; Dietary intake ; Sex difference ; Smoking cessation ; Medicine ; R ; Medicine (General) ; R5-920
Thema/Rubrik (Code)	610 ; 333
Sprache	Englisch
Erscheinungsdatum	2024-02-01T00:00:00Z
Verlag	Elsevier
Dokumenttyp	Artikel ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Artikel ; Online: Deconvolution of bulk blood eQTL effects into immune cell subpopulations

Raúl Aguirre-Gamboa / Niek de Klein / Jennifer di Tommaso / Annique Claringbould / Monique GP van der Wijst / Dylan de Vries / Harm Brugge / Roy Oelen / Urmo Võsa / Maria M. Zorro / Xiaojin Chu / Olivier B. Bakker / Zuzanna Borek / Isis Ricaño-Ponce / Patrick Deelen / Cheng-Jiang Xu / Morris Swertz / Iris Jonkers / Sebo Withoff /

Irma Joosten / Serena Sanna / Vinod Kumar / Hans J. P. M. Koenen / Leo A. B. Joosten / Mihai G. Netea / Cisca Wijmenga / BIOS Consortium / Lude Franke / Yang Li

BMC Bioinformatics, Vol 21, Iss 1, Pp 1-

2020 Band 23

Abstract: Abstract Background Expression quantitative trait loci (eQTL) studies are used to interpret the function of disease-associated genetic risk factors. To date, most eQTL analyses have been conducted in bulk tissues, such as whole blood and tissue biopsies, ...

Abstract	Abstract Background Expression quantitative trait loci (eQTL) studies are used to interpret the function of disease-associated genetic risk factors. To date, most eQTL analyses have been conducted in bulk tissues, such as whole blood and tissue biopsies, which are likely to mask the cell type-context of the eQTL regulatory effects. Although this context can be investigated by generating transcriptional profiles from purified cell subpopulations, current methods to do this are labor-intensive and expensive. We introduce a new method, Decon2, as a framework for estimating cell proportions using expression profiles from bulk blood samples (Decon-cell) followed by deconvolution of cell type eQTLs (Decon-eQTL). Results The estimated cell proportions from Decon-cell agree with experimental measurements across cohorts (R ≥ 0.77). Using Decon-cell, we could predict the proportions of 34 circulating cell types for 3194 samples from a population-based cohort. Next, we identified 16,362 whole-blood eQTLs and deconvoluted cell type interaction (CTi) eQTLs using the predicted cell proportions from Decon-cell. CTi eQTLs show excellent allelic directional concordance with eQTL (≥ 96–100%) and chromatin mark QTL (≥87–92%) studies that used either purified cell subpopulations or single-cell RNA-seq, outperforming the conventional interaction effect. Conclusions Decon2 provides a method to detect cell type interaction effects from bulk blood eQTLs that is useful for pinpointing the most relevant cell type for a given complex disease. Decon2 is available as an R package and Java application ( https://github.com/molgenis/systemsgenetics/tree/master/Decon2 ) and as a web tool ( www.molgenis.org/deconvolution ).
Schlagwörter	eQTL ; Deconvolution ; Cell types ; Immune cells ; Computer applications to medicine. Medical informatics ; R858-859.7 ; Biology (General) ; QH301-705.5
Thema/Rubrik (Code)	571
Sprache	Englisch
Erscheinungsdatum	2020-06-01T00:00:00Z
Verlag	BMC
Dokumenttyp	Artikel ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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