The clustering of human papillomavirus (HPV) infections in some individuals is often interpreted as the result of common risk factors rather than biological interactions between different types of ...HPV. The intraindividual correlation between times-at-risk for all HPV infections is not generally considered in the analysis of epidemiologic studies. We used a deterministic transmission model to simulate cross-sectional and prospective epidemiologic studies measuring associations between 2 HPV types. When we assumed no interactions, the model predicted that studies would estimate odds ratios and incidence rate ratios greater than 1 between HPV types even after complete adjustment for sexual behavior. We demonstrated that this residual association is due to correlation between the times-at-risk for different HPV types, where individuals become concurrently at risk for all of their partners' HPV types when they enter a partnership and are not at risk when they are single. This correlation can be controlled in prospective studies by restricting analyses to susceptible individuals with an infected sexual partner. The bias in the measured associations was largest in low-sexual-activity populations, cross-sectional studies, and studies which evaluated infection with a first HPV type as the exposure. These results suggest that current epidemiologic evidence does not preclude the existence of competitive biological interactions between HPV types.
Highlights • 2-dose girls-only HPV vaccination is likely to be cost-effective if protection is at least 10 years. • A 3rd dose is unlikely to be cost-effective if 2-dose duration of protection is ...longer than 30 years. • Vaccinating boys is unlikely to be cost-effective unless the cost/dose is substantially reduced.
Abstract only
Introduction:
Cancer survivors are at an increased risk for cardiovascular (CV)-related deaths. Recently, clonal hematopoiesis (CH) was described as a novel risk factor for both cancer ...and CV disease. However, the influence of CH on CV outcomes in cancer survivors has not been explored.
Hypothesis:
We hypothesized that CH captured by mosaic chromosomal alterations (mCA) could predict the risk of CV outcomes and death following cancer diagnosis.
Methods:
In the UK Biobank, we identified patients with a history of selected cancer types known for their high CV risk. mCAs were detected using DNA genotyping array intensity data. The association of mCA with CV-death, coronary artery disease (CAD)-death, and any cause death was performed using Cox proportional hazards regression, adjusting for age, sex, smoking, chemotherapy, radiotherapy, and ancestry. Exploratory analyses also included incident CV phenotypes. The specificity of the effect was assessed using a model with an interaction term between mCA and cancer history.
Results:
Among 48 919 unrelated individuals with a cancer diagnosis, 10 070 patients (20.6%) carried ≥1 mCA clone. Of those, 2432 were autosomal carriers and 1910 had a mCA in ≥10% of peripheral leukocytes. mCA prevalence increased with age: from 4.8% among those aged <49 years old to 30.4% for those aged ≥70 years old. mCA was associated with an increased risk of CAD-death (HR 1.37, 95% CI 1.09-1.71,
P=
0.006) and overall mortality (HR 1.07, 95% CI 1.02-1.11,
P
=0.006). In exploratory analyses, mCA was associated with higher risks of incident STEMI (HR 1.18, 95% CI 1.02-1.37,
P
=0.022) and peripheral vascular disease (HR 1.17, 95% CI 1.04-1.31,
P
=0.007). The effect of mCA was specific to cancer survivors for any cause of death (
P
interaction
<0.001) but not for CAD-death (
P
interaction
=0.96).
Conclusions:
Our findings indicate that among cancer survivors, CH captured by mCA was associated with a higher risk of CAD death and overall mortality. Cancer survivors with CH may benefit from targeted CV screening and preventive measures to better manage individual CV risk.
Partitioning of copy-number genotypes in pedigrees Perreault, Louis-Philippe Lemieux; Andelfinger, Gregor U; Asselin, Géraldine ...
BMC bioinformatics,
05/2010, Letnik:
11, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Copy number variations (CNVs) and polymorphisms (CNPs) have only recently gained the genetic community's attention. Conservative estimates have shown that CNVs and CNPs might affect more than 10% of ...the genome and that they may be at least as important as single nucleotide polymorphisms in assessing human variability. Widely used tools for CNP analysis have been implemented in Birdsuite and PLINK for the purpose of conducting genetic association studies based on the unpartitioned total number of CNP copies provided by the intensities from Affymetrix's Genome-Wide Human SNP Array. Here, we are interested in partitioning copy number variations and polymorphisms in extended pedigrees for the purpose of linkage analysis on familial data.
We have developed CNGen, a new software for the partitioning of copy number polymorphism using the integrated genotypes from Birdsuite with the Affymetrix platform. The algorithm applied to familial trios or extended pedigrees can produce partitioned copy number genotypes with distinct parental alleles. We have validated the algorithm using simulations on a complex pedigree structure using frequencies calculated from a real dataset of 300 genotyped samples from 42 pedigrees segregating a congenital heart defect phenotype.
CNGen is the first published software for the partitioning of copy number genotypes in pedigrees, making possible the use CNPs and CNVs for linkage analysis. It was implemented with the Python interpreter version 2.5.2. It was successfully tested on current Linux, Windows and Mac OS workstations.
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