201 research outputs found
sparrpowR: Power Analysis to Detect Spatial Relative Risk Clusters
No full textCalculate the statistical power to detect clusters using kernel-based spatial relative risk functions that are estimated using the 'sparr' package. Details about the 'sparr' package methods can be found in the tutorial: Davies et al. (2018) . Details about kernel density estimation can be found in J. F. Bithell (1990) . More information about relative risk functions using kernel density estimation can be found in J. F. Bithell (1991)
Abstract 1298: Genetic variants related to longer telomere length are associated with increased risk of renal cell carcinoma
No full textAbstract
Telomere length in peripheral blood leukocytes has been evaluated as a potential biomarker for renal cell carcinoma (RCC) risk in numerous observational studies, but association results have been inconsistent. These findings may have been affected by several limitations, including bias from reverse causation, reliance on a single blood specimen, residual confounding or measurement outside of the etiologically relevant time period. Germline genetic variations associated with leukocyte telomere length are not affected by an individual’s exposure to confounders and may act as unconfounded markers of the relationship between telomere length and RCC risk. We performed an analysis of genetic variants associated with leukocyte telomere length to assess the relationship between telomere length and RCC risk. Genotypes from nine telomere length associated variants were aggregated for 10,785 RCC cases and 21,579 cancer-free controls. We found that the number of telomere length variants associated with RCC risk (P-value<0.05) was significantly higher than what would be expected by chance (5/9 variants, binomial P-value=3.32×10−5). We aggregated the telomere length associated variants into a weighted genetic risk score (GRS), where one GRS unit equals to an inferred one Kb change in telomere length. Genetically inferred telomere length was associated with an increased risk of RCC (OR=2.07, 95% CI=1.70-2.52, P-value=7.14×10−13). This association was consistent across increasing deciles of telomere length GRS (Trend P-value=5.58×10−12). As a sensitivity analysis, we removed two telomere length variants in linkage disequilibrium with RCC genome-wide associated regions (rs10936599 and rs9420907) from the telomere length GRS, the association with RCC risk remained statistically significant (OR=1.73, 95% CI=1.35-2.20, P-value=1.07×10−5). When performing analyses by RCC subtype (clear cell=5,574 cases, papillary=573 cases and chromophobe=203 cases), all subtypes investigated showed positive GRS effect estimates, suggesting higher risk for longer telomeres, however, due to limited sample sizes the estimates were only significant for clear cell (OR=1.93, 95% CI=1.50-2.49, P-value=3.79×10−7) and papillary subtypes (OR=1.96, 95% CI=1.01-3.81, P-value=0.046). In conclusion, our results suggest a genetic background that favors longer telomeres is associated with increased RCC risk.
Citation Format: Mitchell J. Machiela, Jonathan N. Hofmann, Robert Carreras-Torres, Nathaniel Rothman, Paul Brennan, Mattias Johansson, Stephen J. Chanock, Kevin M. Brown, Ghislaine Scelo, Mark P. Purdue. Genetic variants related to longer telomere length are associated with increased risk of renal cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1298. doi:10.1158/1538-7445.AM2017-1298</jats:p
LDassoc: an online tool for interactively exploring genome-wide association study results and prioritizing variants for functional investigation
No full textAbstract
Motivation
Existing approaches to plot association results from genome-wide association studies (GWAS) are in the form of static Manhattan plots and often lack data integration with rich databases on variant regulatory potential as well as population-specific linkage disequilibrium patterns.
Summary
We created an intuitive web module for uploading and efficiently exploring GWAS association results. Interactive plots and sortable tables allow researchers to query genomic regions of interest, facilitating the integration of data on linkage disequilibrium, variant regulatory potential and potential target genes. External links allow for visualization of association results in the UCSC genome browser as well as easy access to publically available databases (e.g. dbSNP and RegulomeDB). Through improved visualization and data integration, LDassoc offers genomic researchers a specialized environment to examine association signals and suggests variants for functional investigation.
Availability and implementation
LDassoc is a free and publically available web tool which can be accessed online at https://analysistools.nci.nih.gov/LDlink/? tab=ldassoc.
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Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes
No full text
LDlinkR v1.3.0
No full textGithub repository release #8, LDlinkR v1.3.0:
Change LDlink Domain URL to https://ldlink.nih.gov/ (previous url root will no longer work following an unspecified amount of time).
Add Continuous Integration using Github Actions.
Update citation file with bibentry styl
Risk of clonal hematopoiesis in families exposed to radiation following the Chornobyl accident
No full textRadiation exposure is a well-established risk factor for leukemia. Clonal hematopoiesis (CH), the expansion of mutated hematopoietic cells, is also associated with increased leukemia risk and its frequency is higher in cancer patients following radiotherapy and chemotherapy. We investigated whether low to moderate environmental ionizing radiation determined by state-of-the-art dosimetric analysis was associated with CH in the Chornobyl Family Study (CFS). Our study conducted targeted high-depth sequencing and array genotyping to identify and characterize clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) in 882 participants from 292 CFS families. Fathers had mean bone marrow radiation doses of 0.24 Gy (range: 0-3.86) and mothers had mean doses of 0.009 Gy (range: 2 × 10-5-0.63). The expected relationship between increasing age and CHIP was observed. No detectable effect of red bone marrow radiation dose was observed for CHIP risk (Fathers: Excess OR (EOR)/Gy = 0.41; 95% confidence interval (CI) = -0.57,1.39; P-value = .42; Mothers (categorical model due to limited dose range): odds ratio (OR)0.01-0.09 versus \u3c 0.001 Gy = 0.73; 95% CI = 0.39,1.38; P-value = .33) and the distribution and types of CHIP and mCAs detected in CFS participants did not differ from that seen in previously published studies of unexposed populations. No transgenerational effect of parental gonadal radiation exposure was detected in the children (Fathers: P-value = .08; Mothers: P-value = .67). Our findings suggest the type and levels of radiation exposure investigated in CFS families are unlikely to be strong contributors to CH risk, which could have important implications for public health concerns following environmental exposure to low to moderate ionizing radiation
PCAmatchR: a flexible R package for optimal case–control matching using weighted principal components
No full text- …
