Biology subjects

Allana, S.

Publications and source records attributed to Allana, S..

4 recordsLinked to original sources

bioRxiv2025

GWAS SVatalog: a visualization tool to aid fine-mapping of GWAS loci with structural variations

BackgroundGenome-wide association studies (GWAS) have been successful in identifying single nucleotide polymorphisms (SNPs) associated with phenotypic traits. However, SNPs form an incomplete set of variation across the genome and since a large percentage of GWAS-significant SNPs lie in non-coding regions, their impact on a given trait is difficult to decipher. Recognizing whether these SNPs are tagging other polymorphisms, like structural variations (SV), is an important step towards understanding the putative causal variation at GWAS loci. ResultsHere, we develop GWAS SVatalog (https://svatalog.research.sickkids.ca/), a novel open-source web tool that computes and visualizes linkage disequilibrium (LD) between SVs and GWAS-associated SNPs throughout the human genome. The tool combines GWAS Catalogs SNP-trait association data across 14,479 phenotypes with LD statistics calculated between 35,732 SVs and 116,870 SNPs identified in 101 whole-genome long-read sequences. We use GWAS SVatalog to identify SVs that may explain GWAS loci for iron levels, refractive error, and Alzheimers disease, where previously SNPs were unable to provide a causal explanation. ConclusionsGWAS SVatalog advances the fine-mapping of GWAS loci with structural variations, enabling researchers to associate 35,732 common SVs with 14,479 phenotypes, accelerating the understanding of disease etiology.

bioinformatics↗

bioRxiv2019

Modeling missing cases and transmission links in networks of extensively drug-resistant tuberculosis in KwaZulu-Natal, South Africa

The transmission patterns of drug-resistant tuberculosis (TB) remain poorly understood, despite over half a million incident cases in 2017. Modeling TB transmission networks can provide insight into the nature and drivers of transmission, but incomplete and non-random sampling of TB cases can pose challenges to making inferences from epidemiologic and molecular data. We conducted a quantitative bias analysis to assess the effect of missing cases on a transmission network inferred from Mtb sequencing data on extensively drug-resistant (XDR) TB cases in South Africa. We tested scenarios in which cases were missing at random, differentially by clinical characteristics, or differentially by transmission (i.e., cases with many links were under or over-sampled). Under the assumption cases were missing at random, cases in the complete, modeled network would have had a mean of 20 or more transmission links, which is far higher than expected, in order to reproduce the observed, partial network. Instead, we found that the most likely scenario involved undersampling of high-transmitting cases, and further models provided evidence for superspreading behavior. This is, to our knowledge, the first study to define and assess the support for different mechanisms of missingness in a study of TB transmission. Our findings should caution interpretation of results of future studies of TB transmission in high-incidence settings, given the potential for biased sampling, and should motivate further research aimed at identifying the specific host, pathogen, or environmental factors contributing to superspreading.

epidemiology↗

bioRxiv2017

Polymorphisms in the vitamin D receptor gene are associated with reduced rate of sputum culture conversion in multidrug-resistant tuberculosis patients in South Africa

BackgroundVitamin D modulates the inflammatory and immune response to tuberculosis (TB) and also mediates the induction of the antimicrobial peptide cathelicidin. Deficiency of 25-hydroxyvitamin D and single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene may increase the risk of TB disease and decrease culture conversion rates in drug susceptible TB. Whether these VDR SNPs are found in African populations or impact multidrug-resistant (MDR) TB treatment has not been established. We aimed to determine if SNPs in the VDR gene were associated with sputum culture conversion among a cohort of MDR TB patients in South Africa.\n\nMethodsWe conducted a prospective cohort study of adult MDR TB patients receiving second-line TB treatment in KwaZulu-Natal province. Subjects had monthly sputum cultures performed. In a subset of participants, whole blood samples were obtained for genomic analyses. Genomic DNA was extracted and genotyped with Affymetrix Axiom Pan-African Array. Cox proportional models were used to determine the association between VDR SNPs and rate of culture conversion.\n\nResultsGenomic analyses were performed on 91 MDR TB subjects enrolled in the sub-study; 60% were female and median age was 35 years (interquartile range [IQR] 29-42). Smoking was reported by 21% of subjects and most subjects had HIV (80%), were smear negative (57%), and had cavitary disease (55%). Overall, 87 (96%) subjects initially converted cultures to negative, with median time to culture conversion of 57 days (IQR 17-114). Of 121 VDR SNPs examined, 10 were significantly associated (p<0.01) with rate of sputum conversion in multivariable analyses. Each additional risk allele on SNP rs74085240 delayed culture conversion significantly (adjusted hazard ratio 0.30, 95% confidence interval 0.14-0.67).\n\nConclusionsPolymorphisms in the VDR gene were associated with rate of sputum culture conversion in MDR TB patients in this high HIV prevalence setting in South Africa.\n\nAuthor contributionsMJM, YVS, JCMB, SS, and NRG conceived and designed the study and drafted the initial manuscript. MJM, YVS, YN, and QH performed the data analyses. All authors contributed to interpretation of the data, revised the manuscript, and approved the final version.\n\nThe findings and conclusions in this article are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention (CDC). The use of trade names and commercial sources is for identification only and does not imply endorsement by the CDC.

epidemiology↗

bioRxiv2017

Spatial distribution of extensively drug-resistant tuberculosis (XDR-TB) patients in KwaZulu-Natal, South Africa

BackgroundKwaZulu-Natal province, South Africa, has among the highest burden of XDR-TB worldwide with the majority of cases occurring due to transmission. Poor access to health facilities can be a barrier to timely diagnosis and treatment of TB, which can contribute to ongoing transmission. We sought to determine the geographic distribution of XDR-TB patients and proximity to health facilities in KwaZulu-Natal.\n\nMethodsWe recruited adults and children with XDR-TB diagnosed in KwaZulu-Natal. We calculated distance and time from participants home to the closest hospital or clinic, as well as to the actual facility that diagnosed XDR-TB, using tools within ArcGIS Network analyst. Speed of travel was assigned to road classes based on Department of Transport regulations. Results were compared to guidelines for the provision of social facilities in South Africa: 5km to a clinic and 30km to a hospital.\n\nResultsDuring 2011-2014, 1027 new XDR-TB cases were diagnosed throughout all 11 districts of KwaZulu-Natal, of whom 404 (39%) were enrolled and had geospatial data collected. Participants would have had to travel a mean distance of 2.9 km (CI 95%: 1.8-4.1) to the nearest clinic and 17.6 km (CI 95%: 11.4-23.8) to the nearest hospital. Actual distances that participants travelled to the health facility that diagnosed XDR-TB ranged from <10 km (n=143, 36%) to >50 km (n=109, 27%). The majority (77%) of participants travelled farther than the recommended distance to a clinic (5 km) and 39% travelled farther than the recommended distance to a hospital (30 km). Nearly half (46%) of participants were diagnosed at a health facility in eThekwini district, of whom, 36% resided outside the Durban metropolitan area.\n\nConclusionsXDR-TB cases are widely distributed throughout KwaZulu-Natal province with a denser focus in eThekwini district. Patients travelled long distances to the health facility where they were diagnosed with XDR-TB, suggesting a potential role for migration or transportation in the XDR-TB epidemic.

epidemiology↗