Biology subjects

Thakur, N.

Publications and source records attributed to Thakur, N..

At least 37 records · Page 2Linked to original sources

bioRxiv2021

SARS-CoV-2 variants of concern Alpha, Beta, Gamma and Delta have extended ACE2 receptor host-ranges

Following the emergence of SARS-CoV-2 in China in late 2019 a number of variants have emerged, with two of these - Alpha and Delta - subsequently growing to global prevalence. One characteristic of these variants are changes within the Spike protein, in particular the receptor binding domain (RBD). From a public health perspective these changes have important implications for increased transmissibility and immune escape; however, their presence could also modify the intrinsic host-range of the virus. Using viral pseudotyping we examined whether the variants of concern (VOCs) Alpha, Beta, Gamma and Delta have differing host ACE2 receptor usage patterns, focusing on a range of relevant mammalian ACE2 proteins. All four VOCs were able to overcome a previous restriction for mouse ACE2, with demonstrable differences also seen for individual VOCs with rat, ferret or civet ACE2 receptors, changes which we subsequently attribute to N501Y and E484K substitutions within the Spike RBD.

microbiology↗

bioRxiv2021

Seeing the unseen: A trifoliate (MYB117) mutant allele fortifies folate and carotenoids in tomato fruits

Micronutrient deficiency also termed hidden hunger affects a large segment of the human population, particularly in developing and underdeveloped nations. Tomato the second most consumed vegetable crop in the world after potato can serve as a sustainable source to alleviate micronutrient deficiency. In tomato, the mutations in the R2R3-MYB117 transcription factor elicit trifoliate leaves and initiate axillary meristems; however, its effect on fruit metabolome remains unexplored. The fruits of a new trifoliate (tf) allele (tf-5) were firmer, had higher {degrees}Brix, folate, and carotenoids. The transcriptome, proteome, and metabolome profiling of tf-5 reflected a broad-spectrum change in homeostasis. The tf-5 allele enhanced the fruit firmness by suppressing cell wall softening-related proteins. The tf-5 fruit displayed a substantial increase in aminome, particularly {gamma}-aminobutyric acid, with a parallel reduction in aminoacyl t-RNA synthases. The increased lipoxygenases proteins and transcripts seemingly elevated jasmonic acid. In addition, increased abscisic acid hydrolases transcripts coupled with reduced precursor supply lowered abscisic acid. The upregulation of carotenoids was mediated by modulation of methylerythreitol and plastoquinone pathways along with an increase in carotenoids isomerization proteins. The upregulation of folate in tf-5 was connoted by the increase in precursor p-aminobenzoic acid and transcripts of several folate biosynthesis pathway genes. The reduction in pterin-6-carboxylate and {gamma}-glutamyl hydrolase activity indicated that the diminished folate degradation also enriched folate levels. Our study delineates that introgression of the tf-5 can be used for the {gamma}-aminobutyric acid, carotenoids, and folate fortification of tomato. One-sentence summaryA tomato trifoliate allele encoding a truncated MYB117 transcription factor alters cellular homeostasis and fortifies {gamma}-aminobutyric acid, folate, and carotenoids in tomato fruits.

plant biology↗

bioRxiv2021

Mutations that adapt SARS-CoV-2 to mustelid hosts do not increase fitness in the human airway.

SARS-CoV-2 has a broad mammalian species tropism infecting humans, cats, dogs and farmed mink. Since the start of the 2019 pandemic several reverse zoonotic outbreaks of SARS-CoV-2 have occurred in mink, one of which reinfected humans and caused a cluster of infections in Denmark. Here we investigate the molecular basis of mink and ferret adaptation and demonstrate the spike mutations Y453F, F486L, and N501T all specifically adapt SARS-CoV-2 to use mustelid ACE2. Furthermore, we risk assess these mutations and conclude mink-adapted viruses are unlikely to pose an increased threat to humans, as Y453F attenuates the virus replication in human cells and all 3 mink-adaptations have minimal antigenic impact. Finally, we show that certain SARS-CoV-2 variants emerging from circulation in humans may naturally have a greater propensity to infect mustelid hosts and therefore these species should continue to be surveyed for reverse zoonotic infections.

microbiology↗

bioRxiv2021

Pseudotyped Bat Coronavirus RaTG13 is efficiently neutralised by convalescent sera from SARS-CoV-2 infected Patients

RaTG13 is a close relative of SARS-CoV-2, the virus responsible for the Coronavirus Disease 2019 (COVID-19) pandemic, sharing 96% sequence similarity at the genome-wide level. The spike receptor binding domain (RBD) of RaTG13 contains a large number of amino acid substitutions when compared to SARS-CoV-2, likely impacting affinity for the ACE2 receptor. Antigenic differences between the viruses are less well understood, especially whether RaTG13 spike can be efficiently neutralised by antibodies generated from infection with, or vaccination against, SARS-CoV-2. Using RaTG13 and SARS-CoV-2 pseudotypes we compared neutralisation using convalescent sera from previously infected patients as well as vaccinated healthcare workers. Surprisingly, our results revealed that RaTG13 was more efficiently neutralised than SARS-CoV-2. In addition, neutralisation assays using spike chimeras and mutants harbouring single amino acid substitutions within the RBD demonstrated that both spike proteins can tolerate multiple changes without dramatically reducing how efficiently they are neutralised. Moreover, introducing the 484K mutation into RaTG13 resulted in increased neutralisation, in contrast to the same mutation in SARS-CoV-2 (E484K). This is despite E484K having a well-documented role in immune evasion in variants of concern (VOC) such as B.1.351 (Beta). These results indicate that the immune-escape mutations found in SARS-CoV-2 VOCs might be driven by strong antibody pressures, and that the future spill-over of RaTG13 and/or related sarbecoviruses could be mitigated using current SARS-CoV-2-based vaccination strategies.

microbiology↗

bioRxiv2021

An integrated analysis tool reveals intrinsic biases in gene set enrichment

Generating meaningful interpretations of gene lists remains a challenge for all large-scale studies. Many approaches exist, often based on evaluating gene enrichment among pre-determined gene classes. Here, we conceived and implemented yet another analysis tool (YAAT), specifically for data from the widely-used model organism C. elegans. YAAT extends standard enrichment analyses, using a combination of co-expression data and profiles of phylogenetic conservation, to identify groups of functionally-related genes. It additionally allows class clustering, providing inference of functional links between groups of genes. We give examples of the utility of YAAT for uncovering unsuspected links between genes and show how the approach can be used to prioritise genes for in-depth study. Our analyses revealed several limitations to the meaningful interpretation of gene lists, specifically related to data sources and the "universe" of gene lists used. We hope that YAAT will represent a model for integrated analysis that could be useful for large-scale exploration of biological function in other species.

bioinformatics↗

bioRxiv2021

The ChAdOx1 vectored vaccine, AZD2816, induces strong immunogenicity against SARS-CoV-2 B.1.351 and other variants of concern in preclinical studies.

There is an ongoing global effort to design, manufacture, and clinically assess vaccines against SARS-CoV-2. Over the course of the ongoing pandemic a number of new SARS-CoV-2 virus isolates or variants of concern (VoC) have been identified containing mutations in key proteins. In this study we describe the generation and preclinical assessment of a ChAdOx1-vectored vaccine (AZD2816) which expresses the spike protein of the Beta VoC (B.1.351). We demonstrate that AZD2816 is immunogenic after a single dose. When AZD2816 is used as a booster dose in animals primed with a vaccine encoding the original spike protein (ChAdOx1 nCoV-19/ [AZD1222]), high titre binding and neutralising antibodies against Beta (B.1.351), Gamma (P.1) and Delta (B.1.617.2) are induced. In addition, a strong and polyfunctional T cell response was measured in these booster regimens. These data support the ongoing clinical development and testing of this new variant vaccine.

immunology↗

bioRxiv2021

Circadian regulation of SARS-CoV-2 infection in lung epithelial cells

The COVID-19 pandemic, caused by SARS-CoV-2 coronavirus, is a global health issue with unprecedented challenges for public health. SARS-CoV-2 primarily infects cells of the respiratory tract, via Spike glycoprotein binding angiotensin-converting enzyme (ACE2). Circadian rhythms coordinate an organisms response to its environment and can regulate host susceptibility to virus infection. We demonstrate a circadian regulation of ACE2 in lung epithelial cells and show that silencing BMAL1 or treatment with a synthetic REV-ERB agonist SR9009 reduces ACE2 expression and inhibits SARS-CoV-2 entry. Treating infected cells with SR9009 limits viral replication and secretion of infectious particles, showing that post-entry steps in the viral life cycle are influenced by the circadian system. Transcriptome analysis revealed that Bmal1 silencing induced a wide spectrum of interferon stimulated genes in Calu-3 lung epithelial cells, providing a mechanism for the circadian pathway to dampen SARS-CoV-2 infection. Our study suggests new approaches to understand and improve therapeutic targeting of SARS-CoV-2.

microbiology↗

bioRxiv2020

IBEX: A versatile multi-plex optical imaging approach for deep phenotyping and spatial analysis of cells in complex tissues

The diverse composition of mammalian tissues poses challenges for understanding the cell-cell interactions required for organ homeostasis and how spatial relationships are perturbed during disease. Existing methods such as single-cell genomics, lacking a spatial context, and traditional immunofluorescence, capturing only 2-6 molecular features, cannot resolve these issues. Imaging technologies have been developed to address these problems, but each possesses limitations that constrain widespread use. Here we report a new method that overcomes major impediments to highly multi-plex tissue imaging. Iterative Bleaching Extends multi-pleXity (IBEX) uses an iterative staining and chemical bleaching method to enable high resolution imaging of >65 parameters in the same tissue section without physical degradation. IBEX can be employed with various types of conventional microscopes and permits use of both commercially available and user-generated antibodies in an open system to allow easy adjustment of staining panels based on ongoing marker discovery efforts. We show how IBEX can also be used with amplified staining methods for imaging strongly fixed tissues with limited epitope retention and with oligonucleotide-based staining, allowing potential cross-referencing between flow cytometry, Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-Seq), and IBEX analysis of the same tissue. To facilitate data processing, we provide an open source platform for automated registration of iterative images. IBEX thus represents a technology that can be rapidly integrated into most current laboratory workflows to achieve high content imaging to reveal the complex cellular landscape of diverse organs and tissues. Significance StatementSingle cell flow cytometry and genomic methods are rapidly increasing our knowledge of the diversity of cell types in metazoan tissues. However, suitably robust methods for placing these cells in a spatial context that reveal how their localization and putative interactions contribute to tissue physiology and pathology are still lacking. Here we provide a readily accessible pipeline (IBEX) for highly multi-plex immunofluorescent imaging that enables a fine-grained analysis of cells in their tissue context. Additionally, we describe extensions of the IBEX workflow to handle hard to image tissue preparations and a method to facilitate direct integration of the imaging data with flow cytometry and sequencing technologies.

immunology↗

bioRxiv2020

A booster dose enhances immunogenicity of the COVID-19 vaccine candidate ChAdOx1 nCoV-19 in aged mice

The spread of SARS-CoV-2 has caused a global pandemic that has affected almost every aspect of human life. The development of an effective COVID-19 vaccine could limit the morbidity and mortality caused by infection, and may enable the relaxation of social distancing measures. Age is one of the most significant risk factors for poor health outcomes after SARS-CoV-2 infection, therefore it is desirable that any new vaccine candidates should elicit a robust immune response in older adults. Here, we test the immunogenicity of the adenoviral vectored vaccine ChAdOx1 nCoV-19 (AZD-1222) in aged mice. We find that a single dose of this vaccine induces cellular and humoral immunity in aged mice, but at a reduced magnitude than in younger adult mice. Furthermore, we report that a second dose enhances the immune response to this vaccine in aged mice, indicating that a primeboost strategy may be a rational approach to enhance immunogenicity in older persons.

immunology↗

bioRxiv2020

A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses

There is dire need for an effective and affordable vaccine against SARS-CoV-2 to tackle the ongoing pandemic. In this study, we describe a modular virus-like particle vaccine candidate displaying the SARS-CoV-2 spike glycoprotein receptor-binding domain (RBD) using SpyTag/SpyCatcher technology (RBD-SpyVLP). Low doses of RBD-SpyVLP in a prime-boost regimen induced a strong neutralising antibody response in mice and pigs that was superior to convalescent human sera. We evaluated antibody quality using ACE2 blocking and neutralisation of cell infection by pseudovirus or wild-type SARS-CoV-2. Using competition assays with a monoclonal antibody panel, we showed that RBD-SpyVLP induced a polyclonal antibody response that recognised all key epitopes on the RBD, reducing the likelihood of selecting neutralisation-escape mutants. The induction of potent and polyclonal antibody responses by RBD-SpyVLP provides strong potential to address clinical and logistic challenges of the COVID-19 pandemic. Moreover, RBD-SpyVLP is highly resilient, thermostable and can be lyophilised without losing immunogenicity, to facilitate global distribution and reduce cold-chain dependence.

immunology↗

bioRxiv2020

Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19

Clinical development of the COVID-19 vaccine candidate ChAdOx1 nCoV-19, a replication-deficient simian adenoviral vector expressing the full-length SARS-CoV-2 spike (S) protein was initiated in April 2020 following non-human primate studies using a single immunisation. Here, we compared the immunogenicity of one or two doses of ChAdOx1 nCoV-19 in both mice and pigs. Whilst a single dose induced antigen-specific antibody and T cells responses, a booster immunisation enhanced antibody responses, particularly in pigs, with a significant increase in SARS-CoV-2 neutralising titres.

immunology↗

bioRxiv2020

The SARS-CoV-2 Spike protein has a broad tropism for mammalian ACE2 proteins

SARS-CoV-2 emerged in late 2019, leading to the COVID-19 pandemic that continues to cause significant global mortality in human populations. Given its sequence similarity to SARS-CoV, as well as related coronaviruses circulating in bats, SARS-CoV-2 is thought to have originated in Chiroptera species in China. However, whether the virus spread directly to humans or through an intermediate host is currently unclear, as is the potential for this virus to infect companion animals, livestock and wildlife that could act as viral reservoirs. Using a combination of surrogate entry assays and live virus we demonstrate that, in addition to human ACE2, the Spike glycoprotein of SARS-CoV-2 has a broad host tropism for mammalian ACE2 receptors, despite divergence in the amino acids at the Spike receptor binding site on these proteins. Of the twenty-two different hosts we investigated, ACE2 proteins from dog, cat and rabbit were the most permissive to SARS-CoV-2, while bat and bird ACE2 proteins were the least efficiently used receptors. The absence of a significant tropism for any of the three genetically distinct bat ACE2 proteins we examined indicates that SARS-CoV-2 receptor usage likely shifted during zoonotic transmission from bats into people, possibly in an intermediate reservoir. Interestingly, while SARS-CoV-2 pseudoparticle entry was inefficient in cells bearing the ACE2 receptor from bats or birds the live virus was still able to enter these cells, albeit with markedly lower efficiency. The apparently broad tropism of SARS-CoV-2 at the point of viral entry confirms the potential risk of infection to a wide range of companion animals, livestock and wildlife.

microbiology↗

bioRxiv2020

Pairwise and Higher-Order Epistatic Interactions Have a Significant Impact on Bronchodilator Drug Response in African American Youth with Asthma

BackgroundAsthma is one of the leading chronic illnesses among children in the United States. Asthma prevalence is higher among African Americans (11.2%) compared to European Americans (7.7%). Bronchodilator medications are part of the first-line therapy, and the rescue medication, for acute asthma symptoms. Bronchodilator drug response (BDR) varies substantially among different racial/ethnic groups. Asthma prevalence in African Americans is only 3.5% higher than that of European Americans, however, asthma mortality among African Americans is four times that of European Americans; variation in BDR may play an important role in explaining this health disparity. To improve our understanding of disparate health outcomes in complex phenotypes such as BDR, it is important to consider interactions between environmental and biological variables. ResultsWe evaluated the impact of pairwise and three-variable interactions between environmental, social, and biological variables on BDR in 617 African American youth with asthma using Visualization of Statistical Epistasis Networks (ViSEN). ViSEN is a non-parametric entropy-based approach able to identify interaction effects. We performed analyses in the full dataset and in sex-stratified subsets. Analysis in the full dataset identified six significant interactions associated with BDR, the strongest of which was an interaction between prenatal smoke exposure, age, and global African ancestry (IG: 1.09%, p=0.005). Sex-stratified analyses yielded additional significant, but divergent, results for females and males, indicating the presence of sex-specific effects. ConclusionsOur study identified novel interaction effects significantly influencing BDR in African American children with asthma. Notably, we found that the impact of higher-order interactions was greater than that of pairwise or main effects on BDR highlighting the complexity of the network of genetic and environmental factors impacting this phenotype. Several associations uncovered by ViSEN would not have been detected using regression-based methods emphasizing the importance of employing statistical methods optimized to detect both linear and non-linear interaction effects when studying complex phenotypes such as BDR. The information gained in this study increases our understanding and appreciation of the complex nature of the interactions between environmental and health-related factors that influence BDR and will be invaluable to biomedical researchers designing future studies.

bioinformatics↗

bioRxiv2019

Diversity analysis and metagenomic insights into the Antibiotic Resistance and Metal Resistances among Hot Spring Bacteriobiome- insinuating inherent environmental baseline levels of Antibiotic and Metal tolerance

Mechanisms of occurrence and expressions of antibiotic resistance genes (ARGs) in thermophilic bacteria are still unknown owing to limited research and data. The evolution and proliferation of ARGs in the thermophilic bacteria is unclear and needs a comprehensive study. In this research, comparative profiling of antibiotic resistance genes and metal tolerance genes among the thermophilic bacteria has been done by culture-independent functional metagenomic methods. Metagenomic analysis showed the dominance of Proteobacteria, Actinobacteria. Firmicutes and Bacteroidetes in these hot springs. ARG analysis through shotgun gene sequencing was found to be negative in case of thermophilic bacteria. However, few of genes were detected but they were showing maximum similarity with mesophilic bacteria. Concurrently, metal resistance genes were also detected in the metagenome sequence of hot springs. Detection of metal resistance gene and absence of ARGs investigated by whole genome sequencing, in the reference genome sequence of thermophilic Geobacillus also conveyed the same message. This evolutionary selection of metal resistance over antibiotic genes may have been necessary to survive in the geological craters which are full of different metals from earth sediments rather than antibiotics. Furthermore, the selection could be environment driven depending on the susceptibility of ARGs in thermophilic environment as it reduces the chances of horizontal gene transfer. With these findings this article highlights many theories and culminates different scopes to study these aspects in thermophiles.

microbiology↗

bioRxiv2019

Endophytic Virome

Endophytic microorganisms are well established for their mutualistic relationship and plant growth promotion through production of different metabolites. Bacteria and fungi are the major group of endophytes which were extensively studied. Virus are badly named for centuries and their symbiotic relationship was vague. Recent development of omics tools especially next generation sequencing has provided a new perspective towards the mutualistic viral relationship. Endogenous virus which has been much studied in animal and are less understood in plants. In this study, we described the endophytic viral population of tea plant root. Viral population (9%) were significantly less while compared to bacterial population (90%). Viral population of tea endophytes were mostly dominated by endogenous pararetroviral sequences (EPRV) derived from Caulimoviridae and Geminiviridae. Subclassification of Caulimoviridae showed the dominance of Badnavirus (42%), Caulimovirus (29%), Soymovirus (3%), Tungrovirus (3%), while Geminviridae was only represented by genus Bagmovirus. Interestingly, the endophytic virome sequence from root also showed the presence of phage virus from order Caudovirales. Identified sequence from Caudovirales were Myoviridae and Siphoviridae. Sequence comparison with viral population of soil and root showed the possibility of horizontal transfer of Caudovirales from soil to root environment. This study will expand the knowledge on endogenous viruses especially for tea plant. This study will also help us to understand the symbiotic integration of viral particle with plant which could be used in broader sense to tackle different agronomic problems.\n\nSignificance StatementVirus were badly named for centuries and mostly known for their disease-causing abilities. But recent development of omics tools has focused another facet which is symbiotic. This paper discusses about viral community identified from shotgun sequence of tea root samples which are endogenous in origin. Interestingly, we also identified sequences of phage virus from Caudovirales family which possibly have transmitted from soil. Here we also compared the soil virome community with tea virome to establish the hypothesis. This research will broaden the current knowledge on symbiotic relationship of virus and plant.

microbiology↗

bioRxiv2018

Speed Control and Force-Vectoring of Blue Bottle Flies in a Magnetically-Levitated Flight Mill

Flies fly at a broad range of speeds and produce sophisticated aerial maneuvers with precisely controlled wing movements. Remarkably, only subtle changes in wing motion are used by flies to produce aerial maneuvers, resulting in little directional tilt of aerodynamic force vector relative to the body. Therefore, it is often considered that flies fly according to a helicopter model and control speed mainly via force-vectoring enabled primarily by body-pitch change. Here we examine the speed control of blue bottle flies using a magnetically-levitated (MAGLEV) flight mill, as they fly at different body pitch and with different augmented aerodynamic damping. We identify wing kinematic contributors to the changes of estimated aerodynamic force through testing two force-vectoring models. Results show that in addition to body pitch, flies also use a collection of wing kinematic variables to control both force magnitude and direction, the roles of which are analogous to those of throttle, collective and cyclic pitch of helicopters. Our results also suggest that the MAGLEV flight mill system can be potentially used to study the roles of visual and mechanosensory feedback in insect flight control.\n\nSummary statement: This paper elucidates how files control flight speed while flying in a magnetically-levitated (MAGLEV) flight mill, which enables the manipulation of body pitch and aerodynamic load.

bioengineering↗

bioRxiv2017

Modulatory upregulation of an insulin peptide gene by different pathogens in C. elegans

When an animal is infected, its innate immune response needs to be tightly regulated across tissues and coordinated with other aspects of organismal physiology. Previous studies with Caenorhabditis elegans have demonstrated that insulin-like peptide genes are differentially expressed in response to different pathogens. They represent prime candidates for conveying signals between tissues upon infection. Here, we focused on one such gene, ins-11 and its potential role in mediating cross-tissue regulation of innate immune genes. While diverse bacterial intestinal infections can trigger the up-regulation of ins-11 in the intestine, we show that epidermal infection with the fungus Drechmeria coniospora triggers an upregulation of ins-11 in the epidermis. Using the Shigella virulence factor OpsF, a MAP kinase inhibitor, we found that in both cases, ins-11 expression is controlled cell autonomously by p38 MAPK, but via distinct transcription factors, STA-2/STAT in the epidermis and HLH-30/TFEB in the intestine. We established that ins-11, and the insulin signaling pathway more generally, are not involved in the regulation of antimicrobial peptide gene expression in the epidermis. The up-regulation of ins-11 in the epidermis does, however, affect intestinal gene expression in a complex manner, and has a deleterious effect on longevity. These results support a model in which insulin signaling, via ins-11, contributes to the coordination of the organismal response to infection, influencing the allocation of resources in an infected animal.

genetics↗

bioRxiv2017

A Genome-wide Association and Admixture Mapping Study of Bronchodilator Drug Response in African Americans with Asthma

BackgroundShort-acting B2-adrenergic receptor agonists (SABAs) are the most commonly prescribed asthma medications worldwide. Response to SABAs is measured as bronchodilator drug response (BDR), which varies among racial/ethnic groups in the U.S 1, 2. However, the genetic variation that contributes to BDR is largely undefined in African Americans with asthma3\n\nObjectiveTo identify genetic variants that may contribute to differences in BDR in African Americans with asthma.\n\nMethodsWe performed a genome-wide association study of BDR in 949 African American children with asthma, genotyped with the Axiom World Array 4 (Affymetrix, Santa Clara, CA) followed by imputation using 1000 Genomes phase 3 genotypes. We used linear regression models adjusting for age, sex, body mass index and genetic ancestry to test for an association between BDR and genotype at single nucleotide polymorphisms (SNPs). To increase power and distinguish between shared vs. population-specific associations with BDR in children with asthma, we performed a meta-analysis across 949 African Americans and 1,830 Latinos (Total=2,779). Lastly, we performed genome-wide admixture mapping to identify regions whereby local African or European ancestry is associated with BDR in African Americans. Two additional populations of 416 Latinos and 1,325 African Americans were used to replicate significant associations.\n\nResultsWe identified a population-specific association with an intergenic SNP on chromosome 9q21 that was significantly associated with BDR (rs73650726, p=7.69 x 10-9). A trans-ethnic meta-analysis across African Americans and Latinos identified three additional SNPs within the intron of PRKG1 that were significantly associated with BDR (rs7903366, rs7070958, and rs7081864, p[≤]5 x 10-8).\n\nConclusionsOur findings indicate that both population specific and shared genetic variation contributes to differences in BDR in minority children with asthma, and that the genetic underpinnings of BDR may differ between racial/ethnic groups.\n\nKey messagesO_LIA GWAS for BDR in African American children with asthma identified an intergenic population specific variant at 9q21 to be associated with increased bronchodilator drug response (BDR).\nC_LIO_LIA meta-analysis of GWAS across African Americans and Latinos identified shared genetic variants at 10q21 in the intron of PRKG1 to be associated with differences in BDR.\nC_LIO_LIFurther genetic studies need to be performed in diverse populations to identify the full set of genetic variants that contribute to BDR.\nC_LI

genomics↗