Interpretation of genetic association studies: Markers with replicated highly significant odds ratios may be poor classifiers

Recent successful discoveries of potentially causal single nucleotide polymorphisms (SNPs) for complex diseases hold great promise, and commercialization of genomics in personalized medicine has already begun. The hope is that genetic testing will benefit patients and their families, and encourage positive lifestyle changes and guide clinical decisions. However, for many complex diseases, it is arguable whether the era of genomics in personalized medicine is here yet. We focus on the clinical validity of genetic testing with an emphasis on two popular statistical methods for evaluating markers. The two methods, logistic regression and receiver operating characteristic (ROC) curve analysis, are applied to our age-related macular degeneration dataset. By using an additive model of the CFH, LOC387715, and C2 variants, the odds ratios are 2.9, 3.4, and 0.4, with p-values of 10 -13, 10-13, and 10-3, respectively. The area under the ROC curve (AUC) is 0.79, but assuming prevalences of 15%, 5.5%, and 1.5% (which are realistic for age groups 80 y, 65 y, and 40 y and older, respectively), only 30%, 12%, and 3% of the group classified as high risk are cases. Additionally, we present examples for four other diseases for which strongly associated variants have been discovered. In type 2 diabetes, our classification model of 12 SNPs has an AUC of only 0.64, and two SNPs achieve an AUC of only 0.56 for prostate cancer. Nine SNPs were not sufficient to improve the discrimination power over that of nongenetic predictors for risk of cardiovascular events. Finally, in Crohn's disease, a model of five SNPs, one with a quite low odds ratio of 0.26, has an AUC of only 0.66. Our analyses and examples show that strong association, although very valuable for establishing etiological hypotheses, does not guarantee effective discrimination between cases and controls. The scientific community should be cautious to avoid overstating the value of association findings in terms of personalized medicine before their time. © 2009 Jakobsdottir et al

Brain Activation by Visual Food-Related Stimuli and Correlations with Metabolic and Hormonal Parameters: A fMRI Study

Regional brain activity in 15 healthy, normal weight males during processing of visual food stimuli in a satiated and a hungry state was examined and correlated with neuroendocrine factors known to be involved in hunger and satiated states. Two functional Magnetic Resonance Imaging (fMRI) sessions were performed with a one week interval, after overnight fasting or 1 hour after a standardized meal. Blood samples and appetite assessment were obtained after each fMRI session. Main effects of processing food versus non-food stimuli were observed in the ventral visual stream, including the fusiform gyrus and hippocampal areas bilaterally, significantly more in the fasting state. Leptin concentration correlated negatively with activity in the left hippocampal area and right insula during the satiation condition. A positive correlation between ghrelin and "thought of food" hunger scores were found. The positive correlation between ghrelin and food related activation in the insula areas and the right hippocampus during fasting did not reach significance. Conclusion: The increased activation of food vs non-food pictures in the ventral visual stream reflects increased salience of food pictures when subjects are hungry. Leptin was associated with activations in areas involved in processing of new information and emotion. © Jakobsdottir et al

Dense seismic network provides new insight into the 2007 Upptyppingar dyke intrusion

Factors such as network geometry, network size and phase-picking accuracy have significant\ud effects on the precision of seismic hypocentre locations. In turn, the precision of the hypocentral locations\ud dictates the degree to which morphological details within seismic swarms may be resolved. The Icelandic\ud national seismic network (SIL) is designed to monitor seismic activity across large expanses of Iceland in realtime\ud using automated earthquake detection and location software. Here we examine the performance of the\ud SIL network relative to a much denser, local network of seismometers deployed around the Askja volcano in\ud the Northern Volcanic Zone. A subset of earthquakes from the 2007–2008 dyke intrusion beneath Mt. Upptyppingar\ud is used to compare single- and multi-event hypocentral locations. Specifically, we highlight 288, high\ud signal-to-noise ratio events that occurred during an intensive sequence of earthquakes from 6–24 July 2007,\ud when the temporary Askja network was active. A careful refinement of phase onsets recorded by our wellconfigured,\ud dense network of receivers reveals hypocentres clustered tightly on a planar structure, interpreted\ud as a dyke dipping at 49. The root-mean-square (RMS) misfit to the plane (114 m) is only slightly greater than\ud the uncertainties in relative locations of the earthquakes themselves, and constitutes a three-fold reduction in\ud RMS misfit over SIL relative locations. The improved precision, facilitated predominantly by a more favourable\ud network size and configuration, permits a more detailed analysis of the intrusion

Changes in Insulin-Like Growth Factor-I and -II Associated with Fat but not Lean Mass in Early Old Age

Objective: To test the hypothesis that insulin-like growth factors-I and II (IGF-I and II) decline during late midlife and that greater declines are related to higher fat mass and lower lean mass. Methods: A total of 1,542 men and women in a British birth cohort study had IGF-I and II measured by immunoassay of blood samples at age 53 and/or 60-64 years. Fat mass, android:gynoid fat ratio, and appendicular lean mass were measured at 60-64 years using dual-energy X-ray absorptiometry (DXA). Associations between changes in IGF-I or II and body composition outcomes were examined using conditional change linear regression models. Results: Mean IGF-I and IGF-II concentrations were lower at 60-64 than at 53 years, by 12.8% for IGF-I and by 12.5% for IGF-II. Larger declines in either IGF-I or II were associated with higher fat mass at 60-64 years. Although higher IGF-I at 53 years was associated with higher lean mass, there was little evidence linking changes in IGF-I or II to lean mass. Conclusions: The findings suggest that IGF-I and II concentrations decline with age, and greater declines are associated with higher fat mass levels. These results provide some evidence for the suggested roles of IGF-I and II in regulating fat mass but not lean mass in older age

Using the new information and communication technologies for the continuing professional development of teachers through open and distance learning

We live in a time of rapid and profound change during which both needs and opportunities for professional development keep growing as teachers strive to become lifelong learners. In this chapter, the authors explore how continuing education through open and distance learning (ODL) has evolved for the teaching profession with the use of information and communication technology (ICT). The new ICTs are then discussed and how their uses can be theoretically based, and the use of 3D virtual worlds such as Second LifeTM is examined. A framework for professional development is introduced and two cases of development using the new ICTs and ODL are presented. Problems and challenges are discussed

Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology

Objective: Individuals with obesity and type 2 diabetes differ from lean and healthy individuals in their abundance of certain gut microbial species and microbial gene richness. Abundance of Akkermansia muciniphila, a mucin-degrading bacterium, has been inversely associated with bodyfat mass and glucose intolerance in mice, but more evidence is needed in humans. The impact of diet and weight loss on this bacterial species is unknown. Our objective was to evaluate the association between fecal A. muciniphila abundance, fecal microbiome gene richness, diet, host characteristics, and their changes after calorie restriction (CR). Design: The intervention consisted of a 6-week CR period followed by a 6-week weight stabilization (WS) diet in overweight and obese adults (N=49, including 41 women). Fecal A. muciniphila abundance, fecal microbial gene richness, diet and bioclinical parameters were measured at baseline and after CR and WS. Results: At baseline A. muciniphila was inversely related to fasting glucose, waist-to-hip ratio, and subcutaneous adipocyte diameter. Subjects with higher gene richness and A. muciniphila abundance exhibited the healthiest metabolic status, particularly in fasting plasma glucose, plasma triglycerides and body fat distribution. Individuals with higher baseline A. muciniphila displayed greater improvement in insulin sensitivity markers and other clinical parameters after CR. A. muciniphila was associated with microbial species known to be related to health. Conclusion: A. muciniphila is associated with a healthier metabolic status and better clinicaloutcomes after CR in overweight/obese adults, however the interaction between gut microbiota ecology and A. muciniphila has to be taken into account

Dietary Intakes Among University Students in Iceland : Insights from the FINESCOP Project

Publisher Copyright: © 2025 by the authors.Objectives: Using data from the Food Insecurity among European University Students during the COVID-19 Pandemic (FINESCOP) project, this study aims to investigate the dietary intakes among university students in Iceland, focusing specifically on their current diet after March 2020. Additionally, it examines correlations among different food groups to reveal associations in dietary patterns. Methods: The investigation uses data from the observational FINESCOP project in Iceland. Spearman’s correlation coefficients were used to identify associations between different dietary intakes. p values show significance at a level of <0.05. Results: Icelandic university students have a low intake of vegetables and salad (“3–4 times per week”, n = 159, 24.8%), fruit (“1–2 times per week”, n = 164, 25.6%), and whole wheat (“3–4 times per week”, n = 147, 23.2%). Lower than these was legume intake (“Never/seldom”, n = 203, 32.0%). Meat and eggs were consumed more frequently (“3–4 times per week”, n = 231, 36.3%) compared to fish and seafood (“1–2 times per week”, n = 277, 43.5%). While the findings do indicate a significant correlation between vegetables and salad and fruit intake (p < 0.001) and between vegetable and salad and legume intake (p < 0.001), causal relationships cannot be established. Among discretionary foods, sweets and snacks were moderately and significantly correlated (p < 0.001). Conclusions: This study explores dietary intakes and correlations between dietary factors among university students in Iceland. Further research is needed to explore the potential for causal inferences and better understand these dietary behaviors of university students in Iceland.Peer reviewe

Synthesis and propagation of complement C3 by microglia/monocytes in the aging retina

INTRODUCTION Complement activation is thought to contribute to the pathogenesis of age-related macular degeneration (AMD), which may be mediated in part by para-inflammatory processes. We aimed to investigate the expression and localization of C3, a crucial component of the complement system, in the retina during the course of aging. METHODS SD rats were born and reared in low-light conditions, and euthanized at post-natal (P) days 100, 450, or 750. Expression of C3, IBA1, and Ccl- and Cxcl- chemokines was assessed by qPCR, and in situ hybridization. Thickness of the ONL was assessed in retinal sections as a measure of photoreceptor loss, and counts were made of C3-expressing monocytes. RESULTS C3 expression increased significantly at P750, and correlated with thinning of the ONL, at P750, and up-regulation of GFAP. In situ hybridization showed that C3 was expressed by microglia/monocytes, mainly from within the retinal vasculature, and occasionally the ONL. The number of C3-expressing microglia increased significantly by P750, and coincided spatiotemporally with thinning of the ONL, and up-regulation of Ccl- and Cxcl- chemokines. CONCLUSIONS Our data suggest that recruited microglia/monocytes contribute to activation of complement in the aging retina, through local expression of C3 mRNA. C3 expression coincides with age-related thinning of the ONL at P750, although it is unclear whether the C3-expressing monocytes are a cause or consequence. These findings provide evidence of activation of complement during natural aging, and may have relevance to cellular events underling the pathogenesis of age-related retinal diseases.Funding provided by Australian Research Council Centres of Excellence Program Grant (CE0561903)