Interaction of obesity polygenic score with lifestyle risk factors in an electronic health record biobank

Background Genetic and lifestyle factors have considerable effects on obesity and related diseases, yet their effects in a clinical cohort are unknown. This study in a patient biobank examined associations of a BMI polygenic risk score (PRS), and its interactions with lifestyle risk factors, with clinically measured BMI and clinical phenotypes. Methods The Mass General Brigham (MGB) Biobank is a hospital-based cohort with electronic health record, genetic, and lifestyle data. A PRS for obesity was generated using 97 genetic variants for BMI. An obesity lifestyle risk index using survey responses to obesogenic lifestyle risk factors (alcohol, education, exercise, sleep, smoking, and shift work) was used to dichotomize the cohort into high and low obesogenic index based on the population median. Height and weight were measured at a clinical visit. Multivariable linear cross-sectional associations of the PRS with BMI and interactions with the obesity lifestyle risk index were conducted. In phenome-wide association analyses (PheWAS), similar logistic models were conducted for 675 disease outcomes derived from billing codes. Results Thirty-three thousand five hundred eleven patients were analyzed (53.1% female; age 60.0 years; BMI 28.3 kg/m2), of which 17,040 completed the lifestyle survey (57.5% female; age: 60.2; BMI: 28.1 (6.2) kg/m2). Each standard deviation increment in the PRS was associated with 0.83 kg/m2 unit increase in BMI (95% confidence interval (CI) =0.76, 0.90). There was an interaction between the obesity PRS and obesity lifestyle risk index on BMI. The difference in BMI between those with a high and low obesogenic index was 3.18 kg/m2 in patients in the highest decile of PRS, whereas that difference was only 1.55 kg/m2 in patients in the lowest decile of PRS. In PheWAS, the obesity PRS was associated with 40 diseases spanning endocrine/metabolic, circulatory, and 8 other disease groups. No interactions were evident between the PRS and the index on disease outcomes. Conclusions In this hospital-based clinical biobank, obesity risk conferred by common genetic variants was associated with elevated BMI and this risk was attenuated by a healthier patient lifestyle. Continued consideration of the role of lifestyle in the context of genetic predisposition in healthcare settings is necessary to quantify the extent to which modifiable lifestyle risk factors may moderate genetic predisposition and inform clinical action to achieve personalized medicine.

Clinical patterns, causes, and treatment of torus palatinus

There are two types of tori, including torus palatinus and torus mandibularis. Evidence shows that these lesions usually progress slowly, and a spontaneous growth stop is usually another characteristic. Affected patients are usually asymptomatic. However, symptoms might be reported in edentulous patients and cases when the lesion is huge. In the present study, we elaborated on the causes, clinical patterns, and treatment of torus palatinus. The etiology of the condition is unclear, and different theories were reported in the literature, suggesting that the etiology of these cases is usually attributed to environmental and genetic predisposition. It has been defined as a benign tumor that presents in the maxillary bone and is usually asymptomatic. Therefore, the diagnosis of the condition is usually easy. However, it is recommended to conduct a differential diagnosis with other relevant malignant lesions in this area. Surgical interventions are not usually needed as the condition is usually discovered accidentally. However, in cases of tori-related prosthetic or functional discomfort, surgery can be conducted.

Olfactory Function, Genetic Predisposition, and Cognitive Performance in Chinese adults

Objective: The objective of this study is to examine the association of olfactory function and genetic predisposition of Alzheimer’s disease (AD) with cognitive performance in adults. Methods: A total of 2049 Chinese adults from Rugao Longevity and Ageing Study (RuLAS, n=1460, mean age 78 years) and Central China Cohort (CCC, n=589, mean age 48 years) were included in this study. A standard interview-based survey, clinical information, and blood samples were collected in both cohorts. Olfactory function in terms of olfactory identification was measured by the brief version of the Chinese Smell Identification Test consisted of 18 full points. Cognitive performance was measured by the Chinese version of the Mini-mental State Examination. A genetic risk score (GRS) was calculated from 5 single nucleotide polymorphisms, which were robustly related to Alzheimer’s disease in Caucasians and cognitive performance in our Chinese population. Results: In the pooled analyses, participants at the lowest quartile of olfactory function had significantly higher odds of cognitive impairment (adjusted odds ratio [95% CI] =1.45 [1.00 to 2.09], Ptrend =0.005), and such association was stronger among participants with a stronger genetic predisposition of Alzheimer’s disease (β coefficient±SE, -0.06±0.03 in participants with a lower GRS vs. -0.19±0.05 in those with a higher GRS, respectively, Pinteraction=0.01). Similar associations were observed in RuLAS (P-trend=0.06) and in CCC (P-trend<0.001). Conclusion: In this study, a decreased olfactory function was associated with worse cognitive performance in adults, especially among participants with a higher genetic risk of Alzheimer’s disease. Further studies are warranted to evaluate the causal relationship between olfaction and cognitive performance.

Cardiac Risk Factors for Stroke: A Comprehensive Mendelian Randomization Study

Background and Purpose: Observational studies suggest an association of stroke with cardiac traits beyond atrial fibrillation, the leading source of cardioembolism. However, controversy remains regarding a causal role of these traits in stroke pathogenesis. Here, we leveraged genetic data to systematically assess associations between cardiac traits and stroke risk using a Mendelian Randomization framework. Methods: We studied 66 cardiac traits including cardiovascular diseases, magnetic resonance imaging–derived cardiac imaging, echocardiographic imaging, and electrocardiographic measures, as well as blood biomarkers in a 2-sample Mendelian Randomization approach. Genetic predisposition to each trait was explored for associations with risk of stroke and stroke subtypes in data from the MEGASTROKE consortium (40 585 cases/406 111 controls). Using multivariable Mendelian Randomization, we adjusted for potential pleiotropic or mediating effects relating to atrial fibrillation, coronary artery disease, and systolic blood pressure. Results: As expected, we observed strong independent associations between genetic predisposition to atrial fibrillation and cardioembolic stroke and between genetic predisposition to coronary artery disease as a proxy for atherosclerosis and large-artery stroke. Our data-driven analyses further indicated associations of genetic predisposition to both heart failure and lower resting heart rate with stroke. However, these associations were explained by atrial fibrillation, coronary artery disease, and systolic blood pressure in multivariable analyses. Genetically predicted P-wave terminal force in V1, an electrocardiographic marker for atrial cardiopathy, was inversely associated with large-artery stroke. Conclusions: Available genetic data do not support substantial effects of cardiac traits on the risk of stroke beyond known clinical risk factors. Our findings highlight the need to carefully control for confounding and other potential biases in studies examining candidate cardiac risk factors for stroke.

Legal aspects of using genetic evidence on the example of US judicial practice

Advances in genomic research, biobanking and DNA identification technologies are expanding the use of biological and genetic evidence in litigation. The discovery of DNA and one of its functions to transmit hereditary information made it possible to look differently at the theory of a genetic predisposition to deviant behavior. The relevance of the study is due to the fact that the availability and increase of genetic research allows, along with the traditional use of genetic expertise in litigation (search and identification of a criminal, establishment of paternity), to expand the possibility of using the achievements of genetics by the parties to prove other circumstances in court. In this article, the authors analyze the US jurisprudence regarding the possibility of a party using the protection of genetic evidence in order to present a position in justification of the mitigation of punishment for an accused due to her genetic predisposition to criminal behavior. The authors also paid attention to the consideration of the issue of using the results of genetic testing in civil proceedings in order to prove the fact of the influence of the inherited gene on deviant behavior. In carrying out this study, the authors used a significant number of Russian and foreign sources of scientific literature. General and specific scientific methods of cognition, including the formal legal and comparative legal method, were used as research methods

Phenome-wide association study (PheWAS) of colorectal cancer risk SNP effects on health outcomes in UK Biobank

Background Associations between colorectal cancer (CRC) and other health outcomes have been reported, but these may be subject to biases, or due to limitations of observational studies. Methods We set out to determine whether genetic predisposition to CRC is also associated with the risk of other phenotypes. Under the phenome-wide association study (PheWAS) and tree-structured phenotypic model (TreeWAS), we studied 334,385 unrelated White British individuals (excluding CRC patients) from the UK Biobank cohort. We generated a polygenic risk score (PRS) from CRC genome-wide association studies as a measure of CRC risk. We performed sensitivity analyses to test the robustness of the results and searched the Danish Disease Trajectory Browser (DTB) to replicate the observed associations. Results Eight PheWAS phenotypes and 21 TreeWAS nodes were associated with CRC genetic predisposition by PheWAS and TreeWAS, respectively. The PheWAS detected associations were from neoplasms and digestive system disease group (e.g. benign neoplasm of colon, anal and rectal polyp and diverticular disease). The results from the TreeWAS corroborated the results from the PheWAS. These results were replicated in the observational data within the DTB. Conclusions We show that benign colorectal neoplasms share genetic aetiology with CRC using PheWAS and TreeWAS methods. Additionally, CRC genetic predisposition is associated with diverticular disease.

ProAna Worlds: Affectivity and Echo Chambers Online

Anorexia Nervosa (AN) is an eating disorder characterised by self-starvation. Accounts of AN typically frame the disorder in individualistic terms: e.g., genetic predisposition, perceptual disturbances of body size and shape, experiential bodily disturbances. Without disputing the role these factors may play in developing AN, we instead draw attention to the way disordered eating practices in AN are actively supported by others. Specifically, we consider how Pro-Anorexia (ProAna) websites—which provide support and solidarity, tips, motivational content, a sense of community, and understanding to individuals with AN—help drive and maintain AN practices. We use C. Thi Nguyen’s work on epistemic “echo chambers”, along with Maria Lugones’ work on “worlds” and “ease”, to explore the dynamics of these processes. Adopting this broader temporal and intersubjective perspective, we argue, not only helps to further illuminate the experiential character of AN but also has important clinical and therapeutic significance.