Temporal Patterns in the Evolutionary Genetic Distance of SARS-CoV-2 during the COVID-19 Pandemic

During coronavirus disease 2019 (COVID-19) pandemic, the genetic mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurred frequently. Some mutations in the spike protein are considered to promote transmissibility of the virus, while the mutation patterns in other proteins are less studied and may also be important in understanding the characteristics of SARS-CoV-2. We used the sequencing data of SARS-CoV-2 strains in California to investigate the time-varying patterns of the evolutionary genetic distance. The accumulative genetic distances were quantified across different time periods and in different viral proteins. The increasing trends of genetic distance were observed in spike protein (S protein), the RNA-dependent RNA polymerase (RdRp) region and nonstructural protein 3 (nsp3) of open reading frame 1 (ORF1), and nucleocapsid protein (N protein). The genetic distances in ORF3a, ORF8, and nsp2 of ORF1 started to diverge from their original variants after September 2020. By contrast, mutations in other proteins appeared transiently, and no evident increasing trend was observed in the genetic distance to the original variants. This study presents distinct patterns of the SARS-CoV-2 mutations across multiple proteins from the aspect of genetic distance. Future investigation shall be conducted to study the effects of accumulative mutations on epidemics characteristics.

Unlocking Access to Broad Molecular Profiling: Benefits, Barriers, and Policy Solutions

<b><i>Objectives:</i></b> “Personalized healthcare” is generating new approaches to disease management by considering inter-individual variability in genes, environment, and lifestyle. Technologies such as comprehensive genomic profiling (CGP) are drivers of this shift. Here, we address the significant hurdles to the equitable implementation of CGP into routine clinical practice. <b><i>Methods:</i></b> This article draws on published evidence on the value of genomic profiling, as well as interviews with nine academic and clinical experts from six different countries to validate findings and test policy proposals for reforms. <b><i>Results:</i></b> The potential benefits of CGP extend beyond direct patient outcomes, to healthcare systems with societal and economic impacts. Among key barriers impeding integration into routine clinical practice are the lack of infrastructure to ensure reliable clinical testing and the limited understanding of genomics among healthcare personnel. In addition, the absence of health economic evidence supporting broader use of CGP is creating concerns for payers regarding the systemic benefits and affordability of this technology. <b><i>Conclusion:</i></b> Policy proposals that aim to improve equitable patient access to CGP will need to consider new funding models, health technology assessment processes that capture both patient and systemic benefits, and appropriate regulatory standards to determine the quality of genomic profiling tests.

Comparison of a Cancer Family History Collection and Risk Assessment Tool – ItRunsInMyFamily – with Risk Assessment by Health-Care Professionals

<b><i>Introduction:</i></b> Primary care providers (PCPs) and oncologists lack time and training to appropriately identify patients at increased risk for hereditary cancer using family health history (FHx) and clinical practice guideline (CPG) criteria. We built a tool, “ItRunsInMyFamily” (ItRuns) that automates FHx collection and risk assessment using CPGs. The purpose of this study was to evaluate ItRuns by measuring the level of concordance in referral patterns for genetic counseling/testing (GC/GT) between the CPGs as applied by the tool and genetic counselors (GCs), in comparison to oncologists and PCPs. The extent to which non-GCs are discordant with CPGs is a gap that health information technology, such as ItRuns, can help close to facilitate the identification of individuals at risk for hereditary cancer. <b><i>Methods:</i></b> We curated 18 FHx cases and surveyed GCs and non-GCs (oncologists and PCPs) to assess concordance with ItRuns CPG criteria for referring patients for GC/GT. Percent agreement was used to describe concordance, and logistic regression to compare providers and the tool’s concordance with CPG criteria. <b><i>Results:</i></b> GCs had the best overall concordance with the CPGs used in ItRuns at 82.2%, followed by oncologists with 66.0% and PCPs with 60.6%. GCs were significantly more likely to concur with CPGs (OR = 4.04, 95% CI = 3.35–4.89) than non-GCs. All providers had higher concordance with CPGs for FHx cases that met the criteria for genetic counseling/testing than for cases that did not. <b><i>Discussion/Conclusion:</i></b> The risk assessment provided by ItRuns was highly concordant with that of GC’s, particularly for at-risk individuals. The use of such technology-based tools improves efficiency and can lead to greater numbers of at-risk individuals accessing genetic counseling, testing, and mutation-based interventions to improve health.

“We-Diseases” and Dyadic Decision-Making Processes: A Critical Perspective

This is a critical perspective paper discussing the theoretical bases and methodological issues regarding dyadic decision-making processes in the oncological domain. Decision-making processes are of a central interest when one partner in a couple has cancer, and patients and partners make decisions together under an interactive and dynamic process. Given that, the attention in research is progressively shifting from patient and partner considered as individuals to a more holistic view of patient-partner considered as a dyad. The consideration of the dyadic nature of the decision-making represents a challenge from a theoretical and methodological point of view. The Interdependence Theory and the Dyadic Model of decision-making provide the theoretical bases to consider, respectively, the interdependence of the dyadic decision-making and the mechanisms affecting the couple-based decision-making. Dyadic processes require also an appropriate data analysis strategy that is discussed in the study as well. Conclusions of the present critical review suggest to develop a new line of research on dyadic decision-making in the oncological domain, testing the Dyadic Model presented in the study and considering the interdependence of the data with appropriate levels of analysis.

Association between Genetic Polymorphisms of MIR3142HG and the Risk of Steroid-Induced Osteonecrosis of the Femoral Head in the Population of Northern China

<b><i>Background:</i></b> Steroid-induced osteonecrosis of the femoral head (ONFH) is aseptic necrosis of the femoral head caused by glucocorticoid use. Once necrotic femoral head necrosis occurs, it irreversibly affects the quality of life seriously. Studies have shown that the susceptibility to steroid-induced ONFH is likely to be related to the variation of miRNA-coding genes. Therefore, this study aimed was to investigate the effect of <i>MIR3142HG</i> on steroid-induced ONFH. <b><i>Methods:</i></b> Agena MassARRAY was used to genotype <i>MIR3142HG</i> gene rs1582417, rs2431689, rs7727155, and rs17057846 in 199 patients and 725 healthy people. A genetic model and haplotype analysis were used to evaluate the relationship between the <i>MIR3142HG</i> polymorphism and the risk of steroid-induced ONFH. The odds ratio and 95% confidence intervals were obtained through logistic regression to assess the influence of gene polymorphisms on the occurrence of steroid-induced ONFH. <b><i>Results:</i></b> The consequences show that rs7727115 is a protective factor, it could reduce the risk of steroid-induced ONFH, and rs1582417 could increase the risk of steroid-induced ONFH. In the genetic model, rs1582417 was associated with increased risk of alcohol-induced ONFH in dominant model and log-additive model. rs7727115 showed a decreased risk in codominant model, dominant model, and log-additive model. In addition, rs2431689 is related to HDL-C (<i>p</i> = 0.012) and ApoA1 (<i>p</i> = 0.010) levels, and rs17057846 (<i>p</i> = 0.024) is related to ApoB levels. Thelinkage analysis indicated 3 single-nucleotide polymorphisms (rs2431689, rs7727115, and rs17057846) in <i>MIR3142HG</i> with significant chain imbalance. In addition, haplotype “GGG” of <i>MIR3142HG</i> was found out and is harmful for steroid-induced ONFH. <b><i>Conclusion:</i></b> Our results first confirm that the genetic polymorphism of <i>MIR3142HG</i> is associated with steroid-induced ONFH susceptibility in Chinese Han population.

Identification of Candidate Genes in Early-Stage Invasive Ductal Carcinoma Patients with High-Risk Mortality Using Genes Commonly Involved in Breast Cancer: A Retrospective Study

<b><i>Introduction:</i></b> Invasive ductal carcinoma (IDC) of the breast is a heterogeneous disease characterized by multiple subtypes. IDC survival is highly impacted by tumor burden, molecular subtypes, and gene profiles. Gene mutation is a type of genomic instability regarded as having a considerable effect on IDC prognosis. Using integrated survival analysis, this study identified candidate genes and a high-risk group of patients with early-stage IDC to provide further understanding of the genetic characteristics associated with poor survival. <b><i>Methods:</i></b> The gene mutation profiles, baseline demographics, clinicopathologic variables, and treatment characteristics of the early-stage IDC subpopulation were downloaded from an open access data platform. These data were analyzed for a total of 444 patients. In total, 40 genes commonly involved in IDC were listed, and the genes exhibiting significant differences (as estimated using the log-rank test) were selected as the candidate genes. <b><i>Results:</i></b> The patients were divided into control, low-risk, and high-risk groups according to their gene mutation profiles. The 5-year overall survival rates of low-risk, control, and high-risk patients were 97.4%, 96.1%, and 73.0%, respectively. The high-risk group had a significantly higher risk of poor overall ­survival (adjusted hazard ratio = 6.57, 95% confidence interval = 1.51–28.7, <i>p</i> = 0.012) than that of the control group, and the low-risk group did not have a significant survival difference compared with control group. <b><i>Conclusions:</i></b> This study proposed an integrative approach for the identification of candidate genes for risk assessment of overall survival in these patients through typical survival analysis methods. The 14 candidate genes selected are particularly involved in cell-cycle processes, deoxyribonucleic acid repair, and drug resistance; their mutations were found to be generally associated with disease progression or therapeutic resistance, which is commonly associated with poor overall survival outcomes in IDC.

Altruism as an Explanation for Human Consanguinity

<b><i>Background:</i></b> Human inbreeding is a sociobiological puzzle. Despite widespread knowledge of its potential for genetic disorders, human consanguinity remains surprisingly common. The current reasons explaining its continued persistence in today’s modern world have major shortcomings. <b><i>Summary:</i></b> We propose that the Neolithic Agrarian revolution modified the structure of populations. It increased competition for the limited resources in which a larger group had better chances of survival. As a result, small, drifting, socially open bands of hunter-gatherers were transformed into bigger, less mobile, and more powerful kinship groups (tribes). In this transformation, a central role was played by human trust – an aspect of human altruism which is a universal sociobiological principle of behavior. Altruism (and trust) is an essential premise of social contracts such as economic cooperation, marriage arrangement, and creation of alliances between people. In kinship groups, human trust is limited to kin, so tribes remain small, economically poor, and consanguineous due to lack of nonkin mates. The expanding of trust from kin to that of nonbiological relatives increases the size of human groups, fosters economic wealth, and decreases the rate of consanguinity. <b><i>Key Messages:</i></b> The lack of nonkin altruism leads to: (a) poverty (due to poor economic cooperation with nonkin), (b) maintaining small group size, and (c) inbreeding.

People with Cerebral Palsy and Their Family’s Preferences about Genomics Research

<b><i>Introduction:</i></b> The goal of this study was to understand individuals with cerebral palsy (CP) and their family’s attitudes and preferences to genomic research, including international data sharing and biobanking. <b><i>Methods:</i></b> Individuals with CP and their family members were invited to participate in the web-based survey via email (NSW/ACT CP Register) or via posts on social media by Cerebral Palsy Alliance, CP Research Network, and CP Now. Survey responses included yes/no/unsure, multiple choices, and Likert scales. Fisher’s exact and χ² tests were used to assess if there were significant differences between subgroups. <b><i>Results:</i></b> Individuals with CP and their families (<i>n</i> = 145) were willing to participate in genomics research (68%), data sharing (82%), and biobanking efforts (75%). This willingness to participate was associated with completion of tertiary education, previous genetic testing experience, overall higher genomic awareness, and trust in international researchers. The survey respondents also expressed ongoing communication and diverse information needs regarding the use of their samples and data. Major concerns were associated with privacy and data security. <b><i>Discussion:</i></b> The success of genomic research and international data sharing efforts in CP are contingent upon broad support and recruitment. Ongoing consultation and engagement of individuals with CP and their families will facilitate trust and promote increased awareness of genomics in CP that may in turn maximize participant uptake and recruitment.

Psychological Distress and Quality of Life in Participants Undergoing Genetic Testing for Arrhythmogenic Right Ventricular Cardiomyopathy Caused by TMEM43 p.S358L: Is It Time to Offer Population-Based Genetic Screening?

<b><i>Purpose:</i></b> We have identified 27 families in Newfoundland and Labrador (NL) with the founder variant <i>TMEM43</i> p.S358L responsible for 1 form of arrhythmogenic right ventricular cardiomyopathy. Current screening guidelines rely solely on cascade genetic screening, which may result in unrecognized, high-risk carriers who would benefit from preemptive implantable cardioverter-defibrillator therapy. This pilot study explored the acceptability among subjects to <i>TMEM43</i> p.S358L population-based genetic screening (PBGS) in this Canadian province. <b><i>Methods:</i></b> A prospective cohort study assessed attitudes, psychological distress, and health-related quality of life (QOL) in unselected individuals who underwent genetic screening for the <i>TMEM43</i> p.S358L variant. Participants (<i>n</i> = 73) were recruited via advertisements and completed 2 surveys at baseline, 6 months, and 1 year which measured health-related QOL (SF-36v2) and psychological distress (Impact of Events Scale). <b><i>Results:</i></b> No variant-positive carriers were identified. Of those screened through a telephone questionnaire, &#x3e;95% felt positive about population-genetic screening for <i>TMEM43</i> p.S358L, though 68% reported some degree of anxiety after seeing the advertisement. There were no significant changes in health-related QOL or psychological distress scores over the study period. <b><i>Conclusion:</i></b> Despite some initial anxiety, we show support for PBGS among research subjects who screened negative for the <i>TMEM43</i> p.S358L variant in NL. These findings have implications for future PBGS programs in the province.

Evaluating Primary Care Providers’ Readiness for Delivering Genetic and Genomic Services to Underserved Populations

<b><i>Introduction:</i></b> Increased genomics knowledge and access are advancing precision medicine and care delivery. With the translation of precision medicine across health care, genetics and genomics will play a greater role in primary care services. Health disparities and inadequate representation of racial and ethnically diverse groups threaten equitable access for those historically underserved. Health provider awareness, knowledge, and perceived importance are important determinants of the utilization of genomic applications. <b><i>Methods:</i></b> We evaluated the readiness of primary care providers at a Federally Qualified Health Center, the Community Health Center, Inc. (CHCI) for delivering genetic and genomic testing to underserved populations. Online survey questions focused on providers’ education and training in basic and clinical genetics, familiarity with current genetic tests, and needs for incorporating genetics and genomics into their current practice. <b><i>Results:</i></b> Fifty of 77 (65%) primary care providers responded to the survey. Less than half received any training in basic or clinical genetics (40%), were familiar with specific genetic tests (36%), or felt confident with collecting family health history (44%), and 70% believed patients would benefit from genetic testing. <b><i>Conclusion:</i></b> Despite knowledge gaps, respondents recognized the value and need to bring these services to their patients, though would like more education on applying genetics and genomics into their practice, and more training about discussing risk factors associated with race or ethnicity. We provide further evidence of the need for educational resources and standardized guidelines for providers caring for underserved populations to optimize appropriate use and referral of genetic and genomic services and to reduce disparities in care.