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1.
Geneticists have, for years, understood the nature of genome‐wide association studies using common genomic variants. Recently, however, focus has shifted to the analysis of rare variants. This presents potential problems for researchers, as rare variants do not always behave in the same way common variants do, sometimes rendering decades of solid intuition moot. In this paper, we present examples of the differences between common and rare variants. We show why one must be significantly more careful about the origin of rare variants, and how failing to do so can lead to highly inflated type I error. We then explain how to best avoid such concerns with careful understanding and study design. Additionally, we demonstrate that a seemingly low error rate in next‐generation sequencing can dramatically impact the false‐positive rate for rare variants. This is due to the fact that rare variants are, by definition, seen infrequently, making it hard to distinguish between errors and real variants. Compounding this problem is the fact that the proportion of errors is likely to get worse, not better, with increasing sample size. One cannot simply scale their way up in order to solve this problem. Understanding these potential pitfalls is a key step in successfully identifying true associations between rare variants and diseases. 相似文献
2.
ABSTRACT Tryptophan (Trp) is not only a nutrient enhancer but also has systemic effects. Trp metabolites signaling through the well-known aryl hydrocarbon receptor (AhR) constitute the interface of microbiome-gut-brain axis. However, the pathway through which Trp metabolites affect central nervous system (CNS) function have not been fully elucidated. AhR participates in a broad variety of physiological and pathological processes that also highly relevant to intestinal homeostasis and CNS diseases. Via the AhR-dependent mechanism, Trp metabolites connect bidirectional signaling between the gut microbiome and the brain, mediated via immune, metabolic, and neural (vagal) signaling mechanisms, with downstream effects on behavior and CNS function. These findings shed light on the complex Trp regulation of microbiome-gut-brain axis and add another facet to our understanding that dietary Trp is expected to be a promising noninvasive approach for alleviating systemic diseases. 相似文献
3.
4.
V Aerra M Kuduvalli AN Moloto AK Srinivasan AD Grayson BM Fabri AY Oo 《Journal of cardiothoracic surgery》2006,1(1):6-5
Background
Atrial fibrillation can occur in up to 40% of patients undergoing coronary surgery. 相似文献5.
6.
A new range of stand magnifiers has been released by the COIL company in the United Kingdom. Examination of these magnifiers reveals that they fail to deliver the rated magnifications labelled prominently on the appliances, as a result of the manufacturer's conformance with the requirements of the German DIN standard and the use of back vertex power (F'v) rather than equivalent dioptric power (Fm) of the magnifier. In this study we provide information on the optometric parameters of these new stand magnifiers that will assist the more accurate specification of improvements in vision expected from their use. 相似文献
7.
J. M. Johnston P. Grondziowski R. M. Windisch R. A. Eder L. Lytle 《Acta diabetologica》1995,32(4):213-216
A feasibility study was undertaken to evaluate laboratory phlebotomists performing bedside glucose monitoring (BGM) over a
3-month period on a medical and surgical floor. Specific questions included: feasibility of providing testing on a 24-h basis,
accuracy, appropriate utilization, effect on patient care, and an analysis of cost. In all, 1975 tests were performed on 114
patients. BGM results were within 15% of the laboratory's result 97% of the time. Patient and physician satisfaction was high.
Although the cost of BGM is slightly higher than a laboratory glucose test, its use appeared to reduce the length of hospital
stay by 0.47 days. Practical information on initiating a highly successful BGM program is provided. 相似文献
8.
Sixty-three mallards were fed one of ten poly(methyl methacrylate) based synthetic grit formulations containing varying concentrations of a proposed wildlife contraceptive (nicarbazin), plasticizer (acetyl tributylcitrate) and/or cross-linking agent (1,4-butanediol diacrylate). Release characteristics of the contraceptive agent were monitored for the purpose of developing a contraceptive formulation for control of pest waterfowl in urban settings. The addition of plasticizer increased the erosion rate (t(1/2)=0.97-2.85 days), cross-linking the polymer matrix slightly decreased the erosion rate (t(1/2)=4.45-5.05 days) and increasing the concentration of the contraceptive agent increased the erosion rate (t(1/2)=3.3 and 9.9 days at 60% and 7.5% active ingredient, respectively). The larger and smaller grit pieces had longer half lives at 11.0 and 11.6 days, respectively while the mid sized grit had a half life of 4.95 days. Control grit had a half life of 12.7 days based on weight loss. Analysis of blood and feces for monitoring release from the grit and approximate indirect plasma levels of the active ingredient proved feasible. 相似文献
9.
HLA-DR typing in identical twins with insulin-dependent diabetes: difference between concordant and discordant pairs 总被引:3,自引:0,他引:3
C Johnston D A Pyke A G Cudworth E Wolf 《British medical journal (Clinical research ed.)》1983,286(6361):253-255
A total of 106 pairs of identical twins, of whom 56 were concordant and 50 discordant for insulin-dependent diabetes, were typed for HLA-DR. In both the concordant and discordant groups there was a high prevalence of the antigens DR3 and DR4, a low prevalence of DR5 and DR7, and a virtual absence of DR2. The heterozygous phenotype DR3,DR4 was more prevalent in concordant than discordant pairs. This was therefore the first demonstration of a genetic difference between concordant and discordant identical twin pairs. These findings suggest that possession of both DR3 and DR4 antigens confers a greater genetic predisposition to insulin-dependent diabetes than does the possession of either antigen alone. 相似文献
10.
Paul Wexberg MD BM Richard Pacher MD Suzanne Rdler MD Katharina Kiss MD Gilbert Beran MD Michael Grimm MD Gerald Maurer MD Dietmar Glogar MD FESC 《The Journal of heart and lung transplantation》2002,21(12):583-1263
BACKGROUND: Endothelin, a peptide with strong vasoconstrictive and mitogenic properties, has been found to increase after cardiac transplantation. We therefore assessed the association between its precursor peptide, big endothelin-1, and intimal hyperplasia and coronary flow reserve after heart transplantation. METHODS: Thirty-five patients without hemodynamically significant coronary artery disease after heart transplantation were investigated: Average peak flow velocity in the left anterior descending artery (LAD) was assessed by intracoronary Doppler at baseline as well as after injection of adenosine; coronary flow reserve was calculated as a ratio of both and was corrected for patient age and baseline average peak flow velocity. Lumen, intima + media and total vessel area were measured by intracoronary ultrasound. The plasma concentration of big endothelin-1 in venous blood was determined by radioimmunoassay. RESULTS: Patients with elevated big endothelin-1 levels (>2 fmol/ml) tended to have a decreased corrected coronary flow reserve (2.60 +/- 0.9 vs 3.21 +/- 1.0, p = 0.078). They also had a significantly larger intima + media area (5.82 +/- 2.9 vs 2.37 +/- 2.9 mm(2), p = 0.004) and total vessel area (18.36 +/- 5.8 vs 12.81 +/- 4.8 mm(2), p = 0.012) than those with normal plasma concentrations. CONCLUSIONS: Our study suggests an association between elevated big endothelin-1 plasma levels and the development of intimal hyperplasia and reduction of coronary flow reserve after cardiac transplantation. 相似文献