scholarly journals A Tool for Translating Polygenic Scores onto the Absolute Scale Using Summary Statistics

2021 ◽  
Author(s):  
Oliver Pain ◽  
Alexandra C Gillett ◽  
Jehannine C Austin ◽  
Lasse Folkersen ◽  
Cathryn M Lewis
Keyword(s):  
Absolute Risk ◽  
Absolute Difference ◽  
Summary Statistics ◽  
Mean Absolute Difference ◽  
Polygenic Score ◽  
Absolute Scale ◽  
Polygenic Scores ◽  
The Mean ◽  
The Absolute ◽  
Normally Distributed

Background: There is growing interest in the clinical application of polygenic scores as their predictive utility increases for a range of health-related phenotypes. However, providing polygenic score predictions on the absolute scale is an important step for their safe interpretation. Currently, polygenic scores can only be converted to the absolute scale when a validation sample is available, presenting a major limitation in the interpretability and clinical utility of polygenic scores. Methods: We have developed a method to convert polygenic scores to the absolute scale for binary and normally distributed phenotypes. This method uses summary statistics, requiring only the area-under-the-ROC curve (AUC) or variance explained (R2) by the polygenic score, and the prevalence of binary phenotypes, or mean and standard deviation of normally distributed phenotypes. Polygenic scores are converted using normal distribution theory. Given the AUC/R2 of polygenic scores may be unknown, we also evaluate two methods (AVENGEME, lassosum) for estimating these values from genome-wide association study (GWAS) summary statistics alone. We validate the absolute risk conversion and AUC/R2 estimation using data for eight binary and three continuous phenotypes in the UK Biobank sample. Results: When the AUC/R2 of the polygenic score is known, the observed and estimated absolute values were highly concordant. Across binary phenotypes, the mean absolute difference between the observed and estimated proportion of cases was 5%. For continuous phenotypes, the mean absolute difference between observed and estimated means was <0.3%. Estimates of AUC/R2 from the lassosum pseudovalidation method were most similar to the observed AUC/R2 values, though estimated values deviated substantially from the observed for autoimmune disorders. Conclusion: This study enables accurate interpretation of polygenic scores using only summary statistics, providing a useful tool for educational and clinical purposes. Furthermore, we have created interactive webtools implementing the conversion to the absolute scale for binary and normally distributed phenotypes (https://opain.github.io/GenoPred/PRS_to_Abs_tool.html). Several further barriers must be addressed before clinical implementation of polygenic scores, such as ensuring target individuals are well represented by the GWAS sample.

scholarly journals A tool for translating polygenic scores onto the absolute scale using summary statistics

2022 ◽  
Author(s):  
Oliver Pain ◽  
Alexandra C. Gillett ◽  
Jehannine C. Austin ◽  
Lasse Folkersen ◽  
Cathryn M. Lewis
Keyword(s):  
Genome Wide Association Study ◽  
Absolute Risk ◽  
Summary Statistics ◽  
Clinical Implementation ◽  
Polygenic Score ◽  
Absolute Scale ◽  
Polygenic Scores ◽  
The Absolute ◽  
The Uk ◽  
Normally Distributed

AbstractThere is growing interest in the clinical application of polygenic scores as their predictive utility increases for a range of health-related phenotypes. However, providing polygenic score predictions on the absolute scale is an important step for their safe interpretation. We have developed a method to convert polygenic scores to the absolute scale for binary and normally distributed phenotypes. This method uses summary statistics, requiring only the area-under-the-ROC curve (AUC) or variance explained (R2) by the polygenic score, and the prevalence of binary phenotypes, or mean and standard deviation of normally distributed phenotypes. Polygenic scores are converted using normal distribution theory. We also evaluate methods for estimating polygenic score AUC/R2 from genome-wide association study (GWAS) summary statistics alone. We validate the absolute risk conversion and AUC/R2 estimation using data for eight binary and three continuous phenotypes in the UK Biobank sample. When the AUC/R2 of the polygenic score is known, the observed and estimated absolute values were highly concordant. Estimates of AUC/R2 from the lassosum pseudovalidation method were most similar to the observed AUC/R2 values, though estimated values deviated substantially from the observed for autoimmune disorders. This study enables accurate interpretation of polygenic scores using only summary statistics, providing a useful tool for educational and clinical purposes. Furthermore, we have created interactive webtools implementing the conversion to the absolute (https://opain.github.io/GenoPred/PRS_to_Abs_tool.html). Several further barriers must be addressed before clinical implementation of polygenic scores, such as ensuring target individuals are well represented by the GWAS sample.

scholarly journals Modifying the sternopleural hair pattern in Drosophila by selection

1961 ◽  
Vol 2 (1) ◽  
pp. 158-160 ◽  
Author(s):  
E. C. R. Reeve
Keyword(s):  
Drosophila Melanogaster ◽  
Inbred Lines ◽  
The Other ◽  
Absolute Difference ◽  
Mean Absolute Difference ◽  
Quantitative Characters ◽  
Genetic Behaviour ◽  
The Mean ◽  
Left Right Asymmetry ◽  
Two Sides

Two apparently very similar quantitative characters, the numbers of hairs on the sternopleural region and on the abdominal sternites of Drosophila melanogaster, show unexpected differences in their genetic behaviour. In particular, the amount of left-right asymmetry of the sternopleurals (i.e. the mean absolute difference in numbers of hairs on the two sides of the fly) tends to decline when inbred lines are intercrossed, and can be both increased and decreased by straightforward selection; the corresponding index for the sternite hairs—the uncorrelated variance between two sternites, or the mean absolute difference between the numbers of hairs on each—appears, on the other hand, to be susceptible neither to selection nor to change when inbred lines are crossed (Mather, 1953; Reeve & Robertson, 1954; Reeve, 1959).

Imageless Navigation Accurately Measures Component Orientation during Total Hip Arthroplasty: A Comparison with Postoperative Radiographs

2019 ◽  
Vol 03 (01) ◽  
pp. 053-058 ◽  
Author(s):  
Wayne Paprosky ◽  
Jeffrey Muir ◽  
Jennifer Sostak
Keyword(s):  
Revision Surgery ◽  
Surgical Navigation ◽  
Absolute Difference ◽  
Computer Assisted ◽  
Leg Length ◽  
Acetabular Cup ◽  
Mean Absolute Difference ◽  
Assisted Navigation ◽  
Navigation Tool ◽  
The Mean

AbstractAccurate placement of acetabular components during total hip arthroplasty (THA) is paramount in ensuring long-term stability. Current methods for monitoring cup position and leg length intraoperatively are lacking due to susceptibility to inaccuracy or prohibitive cost. The purpose of this study was to evaluate the ability of an imageless surgical navigation tool to accurately measure acetabular cup inclination and leg length differential during THA. The authors retrospectively reviewed the medical records of patients who underwent primary or revision THA (posterolateral approach) at their facility with the assistance of computer-assisted navigation between February 2016 and March 2017. Pre- and postoperative radiographs were analyzed for leg length discrepancies and acetabular cup inclination. Radiographic values were compared with intraoperative values provided by the surgical navigation tool. The mean difference between inclination as measured from radiographs (44.4 ± 5.9 degrees) and navigation (43.0 ± 4.4 degrees) was −1.4 ± 4.6 degrees (mean absolute difference: 3.8 ± 2.8 degrees). Seventy-seven percent (48/62) of navigation measurements were within 5 degrees of radiographs. The mean difference between radiographic (7.39 ± 5.67 mm) and navigation (7.44 ± 4.81 mm) measurements of leg length differential was 0.29 ± 4.20 mm (mean absolute difference: 3.20 ± 2.69 mm). Navigation tool measurements were within 5 mm of radiographic values in 85% (39/46) of cases. At 90 days, idiopathic dislocation requiring revision surgery occurred in one patient (1.2%) with one additional patient (1.2%) requiring revision surgery due to a traumatic injury (fall). Computer-assisted navigation provided accurate intraoperative data regarding inclination and changes in leg length and was associated with a low rate of dislocation and revision surgery at 90-day follow-up.

scholarly journals A Combined Lidar-Polarimeter Inversion Approach for Aerosol Remote Sensing Over Ocean

2021 ◽  
Vol 2 ◽  
Author(s):  
Feng Xu ◽  
Lan Gao ◽  
Jens Redemann ◽  
Connor J. Flynn ◽  
W. Reed Espinosa ◽  
...  
Keyword(s):  
Size Distribution ◽  
Single Scattering ◽  
Aerosol Size Distribution ◽  
Absolute Difference ◽  
Vertical Profiles ◽  
Mean Absolute Difference ◽  
Surface Reflection ◽  
Aerosol Remote Sensing ◽  
The Mean ◽  
Homogeneous Media

An optimization algorithm is developed to retrieve the vertical profiles of aerosol concentration, refractive index and size distribution, spherical particle fraction, as well as a set of ocean surface reflection properties. The retrieval uses a combined set of lidar and polarimeter measurements. Our inversion includes using 1) a hybrid radiative transfer (RT) model that combines the computational strengths of the Markov-chain and adding-doubling approaches in modeling polarized RT in vertically inhomogeneous and homogeneous media, respectively; 2) a bio-optical model that represents the water-leaving radiance as a function of chlorophyll-a concentration for open ocean; 3) the constraints regarding the smooth variations of several aerosol properties along altitude; and 4) an optimization scheme. We tested the retrieval using 50 sets of coincident lidar and polarimetric data acquired by NASA Langley airborne HSRL-2 and GISS RSP respectively during the ORACLES field campaign. The retrieved vertical profiles of aerosol single scattering albedo (SSA) and size distribution are compared to the reference data measured by University of Hawaii’s HiGEAR instrumentation suite. At the vertical resolution of 315 m, the mean absolute difference (MAD) between retrieved and HiGEAR derived aerosol SSA is 0.028. And the MADs between retrieved and HiGEAR effective radius of aerosol size distribution are 0.012 and 0.377 micron for fine and coarse aerosols, respectively. The retrieved aerosol optical depth (AOD) above aircraft are compared to NASA Ames 4-STAR measurement. The MADs are found to be 0.010, 0.006, and 0.004 for AOD at 355, 532 and 1,064 nm, respectively.

scholarly journals P1559 3D echocardiography improves the agreement between left ventricular and right ventricular stroke volumes in healthy individuals

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
A P Pilalidou ◽  
V K Kantartzi ◽  
C A Adamopoulos ◽  
L Z Zitiridou ◽  
M D Dimtsa ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Left Ventricular ◽  
Absolute Difference ◽  
P Value ◽  
Healthy Individuals ◽  
Mean Absolute Difference ◽  
Mean Values ◽  
Intracardiac Shunt ◽  
The Mean ◽  
The Difference

Abstract Funding Acknowledgements None Background/Introduction: Calculation of the LV and RV stroke volumes (SV) with the volumetric method can be useful for assessment of valvular regurgitant volumes and intracardiac shunt ratios. However, this method often yields significant differences between the estimated LV and RV SV even in healthy subjects. We hypothesized that this discrepancy can be largely due to the assumption of LV and RV outflow tract circularity which forms the basis of 2D derived areas. Purpose To assess if the use of 3D transoesophageal (TOE) derived LVOT and RVOT areas can improve the agreement between LV and RV stroke volumes using the volumetric approach in healthy subjects with no valvular abnormality or intracardiac shunt. Methods We studied 20 patients (9 Males, age: 51 ± 19 y) submitted to TOE for various reasons, who had normal cardiac anatomy and function and good quality 3D TOE LVOT and RVOT data. Two dimensional TOE measurements of the LVOT and RVOT diameters were made in a zoomed mid oesophageal long axis and short axis view respectively; using these measurements 2D TOE LVOT and RVOT derived areas were calculated assuming circularity. In a similar way, we calculated the 2D LVOT and RVOT areas using data from transthoracic echo (TTE) for each patient. Offline analysis of the 3D TOE data allowed direct planimetry of the LVOT and RVOT areas devoid of any geometric assumptions. Finally, calculation of the 2D TTE, 2D TOE and 3D TOE LV and RV stroke volumes were performed for each patient based on the acquired data. The difference between LV and RV stroke volume (which theoretically should be around zero) for each technique and for each patient was also calculated. Results The mean LV and RV SV for the whole cohort, did not differ significantly within each method: 2D-TTE. However, the mean absolute difference between LV and RV stoke volumes for each technique was significantly lower with the use of 3D TOE compared to both 2D TTE and 2D TOE. Mean values and dispersion of absolute differences for each method are shown in Figure 1. Conclusions Compared to 2D, use of direct 3D TOE RVOT and LVOT planimetry yielded significantly less difference between RV and LV stroke volumes in healthy individuals. This finding can have potential clinical implications for more accurate assessment of valvular regurgitant volumes or intracardiac shunts. The mean absolute difference LV-RV Absolute mean defference between LV and RV 95%ΔΕ F(2.38) p-value TTE 2D 18,65 ± 11,72 (13,2-24,1) 8.63 0.001 TOE 2D 13,45 ± 12,44 (7,6-19.3) 8.63 0.001 TOE 3D 6,45 ± 3,62 (4,8-8,1) 8.63 0.001 Abstract P1559 Figure. Bland Altaman Analysis

scholarly journals A benchmarking tool to evaluate computer tomography perfusion infarct core predictions against a DWI standard

2016 ◽  
Vol 36 (10) ◽  
pp. 1780-1789 ◽  
Author(s):  
Carlo W Cereda ◽  
Søren Christensen ◽  
Bruce CV Campbell ◽  
Nishant K Mishra ◽  
Michael Mlynash ◽  
...  
Keyword(s):  
Median Time ◽  
Computer Tomography ◽  
Absolute Difference ◽  
Imaging Data ◽  
Infarct Core ◽  
Mean Absolute Difference ◽  
Software Packages ◽  
Novel Method ◽  
The Mean ◽  
Volumetric Accuracy

Differences in research methodology have hampered the optimization of Computer Tomography Perfusion (CTP) for identification of the ischemic core. We aim to optimize CTP core identification using a novel benchmarking tool. The benchmarking tool consists of an imaging library and a statistical analysis algorithm to evaluate the performance of CTP. The tool was used to optimize and evaluate an in-house developed CTP-software algorithm. Imaging data of 103 acute stroke patients were included in the benchmarking tool. Median time from stroke onset to CT was 185 min (IQR 180-238), and the median time between completion of CT and start of MRI was 36 min (IQR 25-79). Volumetric accuracy of the CTP-ROIs was optimal at an rCBF threshold of <38%; at this threshold, the mean difference was 0.3 ml (SD 19.8 ml), the mean absolute difference was 14.3 (SD 13.7) ml, and CTP was 67% sensitive and 87% specific for identification of DWI positive tissue voxels. The benchmarking tool can play an important role in optimizing CTP software as it provides investigators with a novel method to directly compare the performance of alternative CTP software packages.

scholarly journals Keraring Intrastromal Segment Depth Measured by Spectral-Domain Optical Coherence Tomography in Eyes with Keratoconus

2017 ◽  
Vol 2017 ◽  
pp. 1-9
Author(s):  
Ugo de Sanctis ◽  
Carlo Lavia ◽  
Marco Nassisi ◽  
Savino D’Amelio
Keyword(s):  
Optical Coherence Tomography ◽  
Spectral Domain ◽  
Absolute Difference ◽  
Optical Coherence ◽  
Corneal Surface ◽  
Mean Absolute Difference ◽  
Outer Corner ◽  
Measured Distance ◽  
The Mean ◽  
Belo Horizonte

Purpose. To evaluate agreement between measured and intended distance of Keraring (Mediphacos, Belo Horizonte, Brazil) intracorneal ring segments from the anterior and posterior corneal surfaces.Methods. Twenty-six Keraring ICRS implanted in 24 keratoconic eyes were examined. The distance from the Keraring apex to the anterior corneal surface and the distance from the inner and the outer corners to the posterior corneal surface were measured 3 months postoperatively using spectral-domain optical coherence tomography. Agreement between measured distance and intended distance was assessed by calculating the absolute differences and 95% limits of agreement (95% LoA).Results. The mean absolute difference was significantly lower (p<0.001) for the measurements taken at the inner corner (23.54±15.90 μm) than that for those taken at the apex (108.92±62.72 μm) and the outer corner (108.35±56.99 μm). The measurements taken at the inner corner were within ±25 and ±50 μm of the intended distance in 15/26 (57.7%) and 24/26 (92.3%) cases, respectively, and showed the narrowest 95% LoA with the intended distance (−57.61 to 55.15 μm).Conclusions. The distance of the inner corner from the posterior corneal surface showed the best agreement with the intended distance. This measurement is suitable for determining whether the actual Keraring depth matches the intended depth.

scholarly journals Prior intense exercise reduces arterial carbon dioxide pressure in extreme obesity

2010 ◽  
Vol 33 (5) ◽  
pp. 321 ◽  
Author(s):  
Gerald S Zavorsky ◽  
Do Jun Kim ◽  
Lauren M Cass ◽  
Franco Carli
Keyword(s):  
Carbon Dioxide ◽  
Metabolic Rate ◽  
Arterial Oxygen ◽  
Absolute Difference ◽  
Metabolic Rates ◽  
Extreme Obesity ◽  
Mean Absolute Difference ◽  
Carbon Dioxide Pressure ◽  
Obese Subjects ◽  
The Mean

Purpose: Unlike normal weight individuals, individuals with extreme obesity do not show a decrease in arterial carbon dioxide pressure (PaCO2) from rest to peak exercise. This indicates that breathing is compromised. The objective of this study was to determine if prior high intensity exercise lowers PaCO2 in comparison with a first bout, normalized for the same metabolic rate. Methods: Oxygen consumption during incremental, ramped exercise was matched to constant workload exercise (75% of peak power). Both protocols were to volitional exhaustion 39 ± 8 min apart. Eleven obese subjects (BMI = 47 ± 8 kg/m2, aerobic capacity = 2.3 ± 0.6 L/min) were evaluated. Forty paired samples were obtained at the same metabolic rate between the two protocols. Results: The mean absolute difference and 95% CI were large for arterial oxygen pressure (PaO2) = 9 (6, 11) mmHg and alveolar to arterial oxygen pressure difference (AaDO2) = 7 (5, 8) mmHg. The mean absolute difference for arterial oxyhemoglobin saturation (%SaO2) = 0.5 (0.4, 0.7) %; PaCO2 = 4 (3, 4) mmHg; physiological dead space to tidal volume ratio (VD/VT) = 0.04 (0.03, 0.05); and alveolar ventilation (VA) = 3 (2, 4) L/min. The recovery period after the first bout of exercise reduced the PaCO2 by 3 mmHg when matched for similar metabolic rates. Constant workload exercise predicted VA, %SaO2, VD/VT, and PaCO2, but not PaO2 or AaDO2 during incremental exercise at similar metabolic rates. Conclusion: Given a sufficient chemical stimulus, obese subjects will attempt to breathe more, although this does not mean more VA, which removes CO2.

scholarly journals Accuracy of Vital Signs Measurements by a Smartwatch and a Portable Health Device: Validation Study

10.2196/16811 ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. e16811 ◽  
Author(s):  
Christina Hahnen ◽  
Cecilia G Freeman ◽  
Nilanjan Haldar ◽  
Jacquelyn N Hamati ◽  
Dylan M Bard ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Vital Sign ◽  
Vital Signs ◽  
Final Analysis ◽  
University Hospital ◽  
Health Concern ◽  
Absolute Difference ◽  
Mean Absolute Difference ◽  
The Mean ◽  
Performance Monitor

Background New consumer health devices are being developed to easily monitor multiple physiological parameters on a regular basis. Many of these vital sign measurement devices have yet to be formally studied in a clinical setting but have already spread widely throughout the consumer market. Objective The aim of this study was to investigate the accuracy and precision of heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and oxygen saturation (SpO2) measurements of 2 novel all-in-one monitoring devices, the BodiMetrics Performance Monitor and the Everlast smartwatch. Methods We enrolled 127 patients (>18 years) from the Thomas Jefferson University Hospital Preadmission Testing Center. SBP and HR were measured by both investigational devices. In addition, the Everlast watch was utilized to measure DBP, and the BodiMetrics Performance Monitor was utilized to measure SpO2. After 5 min of quiet sitting, four hospital-grade standard and three investigational vital sign measurements were taken, with 60 seconds in between each measurement. The reference vital sign measurements were calculated by determining the average of the two standard measurements that bounded each investigational measurement. Using this method, we determined three comparison pairs for each investigational device in each subject. After excluding data from 42 individuals because of excessive variation in sequential standard measurements per prespecified dropping rules, data from 85 subjects were used for final analysis. Results Of 85 participants, 36 (42%) were women, and the mean age was 53 (SD 21) years. The accuracy guidelines were only met for the HR measurements in both devices. SBP measurements deviated 16.9 (SD 13.5) mm Hg and 5.3 (SD 4.7) mm Hg from the reference values for the Everlast and BodiMetrics devices, respectively. The mean absolute difference in DBP measurements for the Everlast smartwatch was 8.3 (SD 6.1) mm Hg. The mean absolute difference between BodiMetrics and reference SpO2 measurements was 3.02%. Conclusions Both devices we investigated met accuracy guidelines for HR measurements, but they failed to meet the predefined accuracy guidelines for other vital sign measurements. Continued sale of consumer physiological monitors without prior validation and approval procedures is a public health concern.

scholarly journals In the face of the pandemic, are all equal? On the suitability of the Gini index to monitor time and geographic trends in incidence and death data during the SARS-CoV-2 pandemic

2020 ◽  
Author(s):  
Kirsi Manz ◽  
Ulrich Mansmann
Keyword(s):  
Health Inequalities ◽  
Gini Index ◽  
National Level ◽  
Absolute Difference ◽  
Mean Absolute Difference ◽  
Related Data ◽  
The Face ◽  
Single Positive ◽  
The Mean ◽  
Death Data

AbstractHealth inequalities across nations reinforce social and economic differences. The European Commission has outlined its commitment to reducing health inequalities. The SARS-CoV-2 pandemic is a disruptive event with global, national, and local effects on every aspect of a society’s life. Therefore, it is of interest to quantify and display health (in)equality induced by COVID-19 over time and on different geographic scales (global, continental, national, regional).We aimed to perform a study of (in)equality regarding COVID-19 related data on infections and deaths using the Gini index (GI). A specific focus of our analysis is the (in)equality of infection fatality rates. The Gini index was developed to explore inequality in wealth within or between nations. It is a relative measure which quantifies the ratio of the mean absolute difference between non-negative numerical observations and their mean: GI=0 describes a situation where all values are equal, GI=1 corresponds to one single positive observation among all non-negative observations. We use global, nation- and statewide data to evaluate the inequality at different geographical scales. We also reflect on the suitability of the Gini index to monitor equality aspects of the pandemic.Data from the SARS-CoV-2 pandemic show a considerable amount of inequality in the global distribution of infections and deaths. Only few countries contribute largely to the total infection and death toll. Inequality may result from heterogeneous reporting systems, heterogeneous policy making to fight the pandemic, heterogeneous health systems, and demographic structures. Inequality decreases when going from continental to national or regional levels. Time trends at national level reflect local outbreaks. There is inequality in infection fatality rates, too. Because of equality of income or wealth within a society, low GIs (≤ 0.4) are related to positive connotations like fairness and justice. In the epidemiological setting, however, a GI=1 reflects the goal striven for: The epidemic is restricted to one region while the surroundings are not affected – the epidemic has failed to spread.We used the Gini index to reflect inequality between incidence and death rates of nations or geographic regions. The interpretation of the differences between reported GIs is not straightforward. Furthermore, combined with the information presented by maps, the GI is a useful tool.

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