scholarly journals Genetics of symptom remission in outpatients with COVID-19

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marie-Pierre Dubé ◽  
Audrey Lemaçon ◽  
Amina Barhdadi ◽  
Louis-Philippe Lemieux Perreault ◽  
Essaïd Oussaïd ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Risk Factor ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Natriuretic Peptide Receptor ◽  
Peptide Receptor ◽  
Mechanistic Pathway ◽  
Genome Wide ◽  
A Genome ◽  
Symptom Remission

AbstractWe conducted a genome-wide association study of time to remission of COVID-19 symptoms in 1723 outpatients with at least one risk factor for disease severity from the COLCORONA clinical trial. We found a significant association at 5p13.3 (rs1173773; P = 4.94 × 10–8) near the natriuretic peptide receptor 3 gene (NPR3). By day 15 of the study, 44%, 54% and 59% of participants with 0, 1, or 2 copies of the effect allele respectively, had symptom remission. In 851 participants not treated with colchicine (placebo), there was a significant association at 9q33.1 (rs62575331; P = 2.95 × 10–8) in interaction with colchicine (P = 1.19 × 10–5) without impact on risk of hospitalisations, highlighting a possibly shared mechanistic pathway. By day 15 of the study, 46%, 62% and 64% of those with 0, 1, or 2 copies of the effect allele respectively, had symptom remission. The findings need to be replicated and could contribute to the biological understanding of COVID-19 symptom remission.

scholarly journals Genetics of symptom remission in outpatients with COVID-19

2021 ◽  
Author(s):  
Marie-Pierre Dubé ◽  
Audrey Lemaçon ◽  
Amina Barhdadi ◽  
Louis-Philippe Lemieux Perreault ◽  
Essaïd Oussaïd ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Risk Factor ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Natriuretic Peptide Receptor ◽  
Peptide Receptor ◽  
Mechanistic Pathway ◽  
Genome Wide ◽  
A Genome ◽  
Symptom Remission

ABSTRACTWe conducted a genome-wide association study of time to remission of COVID-19 symptoms in 1723 outpatients with at least one risk factor for disease severity from the COLCORONA clinical trial. We found a significant association at 5p13.3 (rs1173773; P = 4.94 × 10−8) near the natriuretic peptide receptor 3 gene (NPR3). By day 15 of the study, 44%, 54% and 59% of participants with 0, 1, or 2 copies of the effect allele respectively, had symptom remission. In 851 participants not treated with colchicine (placebo), there was a significant association at 9q33.1 (rs62575331; P = 2.95 × 10−8) in interaction with colchicine (P = 1.19 × 10−5) without impact on risk of hospitalisations, highlighting a possibly shared mechanistic pathway. By day 15 of the study, 46%, 62% and 64% of those with 0, 1, or 2 copies of the effect allele respectively, had symptom remission. The findings need to be replicated and could contribute to the biological understanding of COVID-19 symptom remission.

Abstract 16003: Genetic Variation Associated With Favorable Exercise Response in Patients With Systolic Heart Failure: A Hf-action Trial Substudy

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Sara Coles ◽  
Stephanie Giamberardino ◽  
Carol Haynes ◽  
Ruicong She ◽  
Hongsheng Gui ◽  
...  
Keyword(s):  
Heart Failure ◽  
Clinical Trial ◽  
Genome Wide Association Study ◽  
Meta Analysis ◽  
Systolic Heart Failure ◽  
Genome Wide Association ◽  
Supervised Exercise ◽  
Genome Wide ◽  
A Genome ◽  
Response To Exercise

Background: Exercise has shown benefit in patients with systolic heart failure, including in the clinical trial Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION). There is heterogeneity in who derives benefit from exercise, and the biologic mechanisms of favorable response to exercise in systolic heart failure are not well understood. Hypothesis: Genetic variation is an underlying factor influencing heterogeneity in response to exercise in patients with systolic heart failure. Methods: The HF-ACTION trial randomized individuals with systolic heart failure (left ventricular ejection fraction <35%) to supervised exercise versus usual care. In this study, we performed a genome wide association study (GWAS) in the HF-ACTION biorepository using the Axiom Biobank1 genotyping array (13,403,591 single nucleotide polymorphisms [SNPs] after quality control on directly genotyped and 1000 genomes imputed data), in N=377 study subjects who completed the supervised exercise arm. Using change in peak VO2 as our outcome, we ran within-ancestry GWASes, modeling SNP effects as both additive and dominant, and conducted across-ancestry meta-analysis within each genetic model. Results: Five loci met genome-wide significance in the European ancestry analyses, 5 loci in the African ancestry, and 8 in the meta-analyses. The two most significantly associated loci across both additive and dominant meta-analysis models were rs111577308 located in the histone acetylation for transcription elongator complex 3 gene ( ELP3, p=1.212x10 -9 ) and rs75444785 located in the phosphodiesterase 4D gene ( PDE4D , p=1.565x10 -9 ). ELP3 is responsible for histone modifications related to DNA transcription factor complexes, and PDE4D is involved in cyclic AMP cell signaling. In silico analysis of these loci showed that they are in linkage with regions associated with skeletal muscle and peripheral vascular disease phenotypes. Conclusions: Using a genome-wide association study in a well-phenotyped clinical trial of exercise in systolic heart failure, we found common genetic variants in genes involved in DNA transcription histone modification and cyclic AMP cell signaling that are associated with a more favorable response to exercise.

scholarly journals A genome wide association study identifies a lncRna as risk factor for pathological inflammatory responses in leprosy

PLoS Genetics ◽  
2017 ◽  
Vol 13 (2) ◽  
pp. e1006637 ◽  
Author(s):  
Vinicius M. Fava ◽  
Jeremy Manry ◽  
Aurélie Cobat ◽  
Marianna Orlova ◽  
Nguyen Van Thuc ◽  
...  
Keyword(s):  
Risk Factor ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Inflammatory Responses ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome

A genome-wide association study (GWAS) of docetaxel-induced peripheral neuropathy in CALGB 90401 (Alliance).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11053-11053
Author(s):  
Daniel Louis Hertz ◽  
Kouros Owzar ◽  
Susan Halabi ◽  
William Kevin Kelly ◽  
Hitoshi Zembutsu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Clinical Trial ◽  
Peripheral Neuropathy ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome ◽  
Grade 3

11053 Background: There are currently no effective methods for predicting, preventing, or treating chemotherapy-induced peripheral neuropathy. We performed a genome-wide association study in a clinical trial of castration-resistant prostate cancer (CRPC) to discover variants that may be useful for identifying patients at high risk of neuropathy during docetaxel treatment. Methods: Treatment and toxicity data were collected prospectively on the Cancer and Leukemia Group B (CALGB) 90401 trial of chemotherapy naïve CRPC patients treated with docetaxel and prednisone ± bevacizumab. Genotyping was performed by the RIKEN Institute using the Illumina HumanHap610-Quad platform. Genetically defined European subjects were included in the discovery analysis of all single nucleotide polymorphisms (SNPs) that passed quality control. The primary endpoint was the cumulative dose level triggering a grade 3+ sensory neuropathy. The inference was conducted within the framework of a competing risk model accounting for early treatment termination induced by death or progression, or other toxicities. SNPs that were highly associated with neuropathy were assessed for a broader taxane effect in a cohort of paclitaxel-treated patients from a breast cancer clinical trial, CALGB 40101. Results: 623 Caucasian patients and 498,022 SNPs were included in the discovery analysis. The incidence of grade 3 neuropathy was 8%. One intergenic SNP (rs11017056) was associated with increased risk of neuropathy (HR=2.83, p=4.7x10-7). This association surpassed the genome-wide significance threshold after covariate adjustment (p=7.2x10-8). However, none of the 7 SNPs selected for replication were associated with neuropathy in the paclitaxel-treated breast cancer cohort. Conclusions: Using a prospectively enrolled prostate cancer patient cohort we identified multiple SNPs that may identify risk of docetaxel-induced peripheral neuropathy, but not paclitaxel-induced neuropathy. However, since it is unknown whether the genetic factors that affect taxane neuropathy are drug-specific, further replication studies in docetaxel-treated cohorts are of great interest.

scholarly journals A genome-wide association study implicates the BMP7 locus as a risk factor for nonsyndromic metopic craniosynostosis

2020 ◽  
Vol 139 (8) ◽  
pp. 1077-1090 ◽  
Author(s):  
Cristina M. Justice ◽  
◽  
Araceli Cuellar ◽  
Krithi Bala ◽  
Jeremy A. Sabourin ◽  
...  
Keyword(s):  
Risk Factor ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome ◽  
Metopic Craniosynostosis

scholarly journals A genome-wide association study identifies 5 loci associated with frozen shoulder and implicates diabetes as a causal risk factor

PLoS Genetics ◽  
2021 ◽  
Vol 17 (6) ◽  
pp. e1009577
Author(s):  
Harry D. Green ◽  
Alistair Jones ◽  
Jonathan P. Evans ◽  
Andrew R. Wood ◽  
Robin N. Beaumont ◽  
...  
Keyword(s):  
Risk Factor ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Frozen Shoulder ◽  
Genome Wide Association ◽  
Biological Mechanisms ◽  
Painful Condition ◽  
Causal Risk Factor ◽  
Genome Wide ◽  
A Genome

Frozen shoulder is a painful condition that often requires surgery and affects up to 5% of individuals aged 40–60 years. Little is known about the causes of the condition, but diabetes is a strong risk factor. To begin to understand the biological mechanisms involved, we aimed to identify genetic variants associated with frozen shoulder and to use Mendelian randomization to test the causal role of diabetes. We performed a genome-wide association study (GWAS) of frozen shoulder in the UK Biobank using data from 10,104 cases identified from inpatient, surgical and primary care codes. We used data from FinnGen for replication and meta-analysis. We used one-sample and two-sample Mendelian randomization approaches to test for a causal association of diabetes with frozen shoulder. We identified five genome-wide significant loci. The most significant locus (lead SNP rs28971325; OR = 1.20, [95% CI: 1.16–1.24], p = 5x10-29) contained WNT7B. This variant was also associated with Dupuytren’s disease (OR = 2.31 [2.24, 2.39], p<1x10-300) as were a further two of the frozen shoulder associated variants. The Mendelian randomization results provided evidence that type 1 diabetes is a causal risk factor for frozen shoulder (OR = 1.03 [1.02–1.05], p = 3x10-6). There was no evidence that obesity was causally associated with frozen shoulder, suggesting that diabetes influences risk of the condition through glycemic rather than mechanical effects. We have identified genetic loci associated with frozen shoulder. There is a large overlap with Dupuytren’s disease associated loci. Diabetes is a likely causal risk factor. Our results provide evidence of biological mechanisms involved in this common painful condition.

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