Journal of Community Genetics最新文献

A large number of studies have reported that the prevalence of beta thalassemia carriers in India varies by ethnic groups. The objective of this study was to conduct a systematic review of the published studies and conduct a meta-analysis to determine the prevalence of beta thalassaemia carriers in India. A PubMed database search using keywords "beta thalassaemia AND India" identified 1088 articles of which 69 articles were included in the review. Studies using diagnostic tests and methods recommended by the International Council for Standardization in Haematology were used for calculation of pooled prevalence. Pooled prevalence was calculated using a random effects model using Review Manager version 5.3. Studies had screened five categories of populations, that is, the general population; tribal groups, communities not belonging to tribal groups, persons with anemia, and persons referred with a suspicion of hemoglobinopathy. This heterogeneity contributed to a high pooled prevalence of beta thalassemia carriers of 8.23% (95% CI 7.36-9.10). Sub-group analysis however yielded 3.74% (95% CI 2.52-4.97) pooled prevalence of beta thalassemia carriers in the general population. It was 4.6% (95% CI 3.2-6.2) among tribal groups. Quality of prevalence studies was limited by methodological issues including non-random sampling methods, heterogeneity of population types screened, and lack of use of recommended diagnostic cut-offs. Prevalence of beta thalassemia carriers was similar in tribal populations and the general population, indicating the need to further investigate the prevalence of beta thalassemia carriers in tribal groups.

Genome-wide association studies (GWAS) have allowed the identification of disease-associated variants, which can be leveraged to build polygenic scores (PGSs). Even though PGSs can be a valuable tool in personalized medicine, their predictive power is limited in populations of non-European ancestry, particularly in admixed populations. Recent efforts have focused on increasing racial and ethnic diversity in GWAS, thus, addressing some of the limitations of genetic risk prediction in these populations. Even with these efforts, few studies focus exclusively on Hispanics/Latinos. Additionally, Hispanic/Latino populations are often considered a single population despite varying admixture proportions between and within ethnic groups, diverse genetic heterogeneity, and demographic history. Combined with highly heterogeneous environmental and socioeconomic exposures, this diversity can reduce the transferability of genetic risk prediction models. Given the recent increase of genomic studies that include Hispanics/Latinos, we review the milestones and efforts that focus on genetic risk prediction, summarize the potential for improving PGS transferability, and highlight the challenges yet to be addressed. Additionally, we summarize social-ethical considerations and provide ideas to promote genetic risk prediction models that can be implemented equitably.

Caregivers caring for a child with a genetic condition may experience psychosocial distress, which may be compounded by the context in which the caring takes place. Few studies have examined psychosocial distress and support among caregivers caring for a child with a genetic disorder in low-middle-income countries such as Ghana. The purpose of the current study was to investigate the psychosocial impacts of caring for a child with a genetic disorder in an urban setting in Ghana's capital, Accra. We conducted individual interviews among 17 caregivers who were taking care of children with various genetic disorders including, albinism, Edward's syndrome, osteogenesis imperfecta, sickle cell disease, and spondyloepiphyseal dysplasia congenita. Thematic analysis of the data revealed three main themes on the psychosocial impacts, including: (1) self-blame, guilt, and shame; (2) sleep and mood disturbances; and (3) discrimination and stigmatization. We observed three themes about support: (1) psychological support; (2) family and community support; and (3) institutional support. Participants reported limited support from professionals such as psychologists. Discussion focuses on the supportive care needs of caregivers and implications for genetic counselling awareness, advocacy, and training.

Newborn screening in Alaska includes screening for carnitine palmitoyltransferase 1A (CPT1A) deficiency. The CPT1A Arctic variant is a variant highly prevalent among Indigenous peoples in the Arctic. In this study, we sought to elicit Alaska Native (AN) community member and AN-serving healthcare providers' knowledge and perspectives on the CPT1A Arctic variant. Focus groups with community members and healthcare providers were held in two regions of Alaska between October 2018 and January 2019. Thematic analysis was used to identify recurring constructs. Knowledge and understanding about the CPT1A Arctic variant and its health impact varied, and participants were interested in learning more about it. Additional education for healthcare professionals was recommended to improve providers' ability to communicate with family caregivers about the Arctic variant. Engagement with AN community members identified opportunities to improve educational outreach via multiple modalities for providers and caregivers on the Arctic variant, which could help to increase culturally relevant guidance and avoid stigmatization, undue worry, and unnecessary intervention. Education and guidance on the care of infants and children homozygous for the CPT1A Arctic variant could improve care and reduce negative psychosocial effects.

Since their first appearance in the context of schizophrenia and bipolar disorder in 2009, polygenic risk scores (PRSs) have been described for a large number of common complex diseases. However, the clinical utility of PRSs in disease risk assessment or therapeutic decision making is likely limited because PRSs usually only account for the heritable component of a trait and ignore the etiological role of environment and lifestyle. We surveyed the current state of PRSs for various diseases, including breast cancer, diabetes, prostate cancer, coronary artery disease, and Parkinson disease, with an extra focus upon the potential improvement of clinical scores by their combination with PRSs. We observed that the diagnostic and prognostic performance of PRSs alone is consistently low, as expected. Moreover, combining a PRS with a clinical score at best led to moderate improvement of the power of either risk marker. Despite the large number of PRSs reported in the scientific literature, prospective studies of their clinical utility, particularly of the PRS-associated improvement of standard screening or therapeutic procedures, are still rare. In conclusion, the benefit to individual patients or the health care system in general of PRS-based extensions of existing diagnostic or treatment regimens is still difficult to judge.

Advances in genomics have enabled the development of polygenic scores (PGS), sometimes called polygenic risk scores, in the context of multifactorial diseases and disorders such as cancer, cardiovascular disease, and schizophrenia. PGS estimate an individual's genetic predisposition, as compared to other members of a population, for conditions which are influenced by both genetic and environmental factors. There is significant interest in using genetic risk prediction afforded through PGS in public health, clinical care, and research settings, yet many acknowledge the need to thoughtfully consider and address ethical, legal, and social implications (ELSI). To contribute to this effort, this paper reports on a narrative review of the literature, with the aim of identifying and categorizing ELSI relating to genetic risk prediction in the context of multifactorial disease, which have been raised by scholars in the field. Ninety-two articles, spanning from 1977 to 2021, met the inclusion criteria for this study. Identified ELSI included potential benefits, challenges and risks that focused on concerns about interpretation and use, and ethical obligations to maximize benefits, minimize risks, promote justice, and support autonomy. This research will support geneticists, clinicians, genetic counselors, patients, patient advocates, and policymakers in recognizing and addressing ethical concerns associated with PGS; it will also guide future empirical and normative research.

The aim of this patient and public involvement and engagement (PPIE) work was to explore improvised theatre as a tool for facilitating bi-directional dialogue between researchers and patients/members of the public on the topic of polygenic risk scores (PRS) use within primary or secondary care. PRS are a tool to quantify genetic risk for a heritable disease or trait and may be used to predict future health outcomes. In the United Kingdom (UK), they are often cited as a next-in-line public health tool to be implemented, and their use in consumer genetic testing as well as patient-facing settings is increasing. Despite their potential clinical utility, broader themes about how they might influence an individual's perception of disease risk and decision-making are an active area of research; however, this has mostly been in the setting of return of results to patients. We worked with a youth theatre group and patients involved in a PPIE group to develop two short plays about public perceptions of genetic risk information that could be captured by PRS. These plays were shared in a workshop with patients/members of the public to facilitate discussions about PRS and their perceived benefits, concerns and emotional reactions. Discussions with both performers and patients/public raised three key questions: (1) can the data be trusted?; (2) does knowing genetic risk actually help the patient?; and (3) what makes a life worthwhile? Creating and watching fictional narratives helped all participants explore the potential use of PRS in a clinical setting, informing future research considerations and improving communication between the researchers and lay members of the PPIE group.

Polygenic risk scores (PRS) have the potential to improve the accuracy of clinical risk assessments, yet questions about their clinical validity and readiness for clinical implementation persist. Understanding how individuals integrate and act on the information provided by PRS is critical for their effective integration into routine clinical care, yet few studies have examined how individuals respond to the receipt of polygenic risk information. We conducted an embedded Ethical, Legal, and Social Implications (ELSI) study to examine if and how unaffected participants in a US population breast cancer screening trial understood and utilized PRS, as part of a multifactorial risk score combining traditional risk factors with a genetic risk assessment, to make screening and risk-reduction decisions. Semi-structured qualitative interviews were conducted with 24 trial participants who were designated at elevated risk for breast cancer due to their combined risk score. Interviews were analyzed using a grounded theory approach. Participants understood PRS conceptually and accepted it as one of many risk factors to consider, yet the value and meaning they ascribed to this risk estimate varied. Most participants reported financial and insurance barriers to enhanced screening with MRI and were not interested in taking risk-reducing medications. These findings contribute to our understanding of how PRS may be best translated from research to clinical care. Furthermore, they illuminate ethical concerns about identifying risk and making recommendations based on polygenic risk in a population screening context where many may have trouble accessing appropriate care.

As genomic technologies rapidly develop, polygenic scores (PGS) are entering into a growing conversation on how to improve precision in public health and prevent chronic disease. While the integration of PGS into public health and clinical services raises potential benefits, it also introduces potential harms. In particular, there is a high level of uncertainty about how to incorporate PGS into clinical settings in a manner that is equitable, just, and aligned with the long-term goals of many healthcare systems to support person-centered and value-based care. This paper argues that any conversation about whether and how to design and implement PGS clinical services requires dynamic engagement with local communities, patients, and families. These parties often face the consequences, both positive and negative, of such uncertainties and should therefore drive clinical translation. As a collaborative effort between hospital stakeholders, community partners, and researchers, this paper describes a community-empowered co-design process for addressing uncertainty and making programmatic decisions about the implementation of PGS into clinical services. We provide a framework for others interested in designing clinical programs that are responsive to, and inclusive and respectful of, local communities.