Public Health Genetics Research Articles

Prevalence of Trehalase Enzymopathy Genetic Determinants in Siberian and Russian Far East Populations.

. Using the Infinium iSelect HD Custom BeadChip biochip (Illumina, United States) on the iScan platform and real-time polymerase chain reaction on a Bio-Rad CFX96 Touch amplifier, genotyping of 1068 DNA samples was carried out, of which 667 represent 10 ethnic groups of the indigenous people of the North of Siberia and the Far East of the Russian Federation. Two reference groups (357 samples) of Russians (n=311) and Yakuts (n = 46) represent the "Caucasoid" and "Mongoloid" poles of the Russian population. : The reduced trehalase activity that the heterozygous GA*TREH genotype determines can manifest itself in 19.8-53.7% of indigenous northerners. An additional 1.0 to 19.7% of the population are carriers of the AA*TREH genotype, which is associated with apparent trehalose malabsorption. The carriers may experience nausea, abdominal pain, and other dyspeptic symptoms after eating trehalose containing foods. The total risk of trehalase enzymopathy among the indigenous northerners in the Asian part of the Russian Federation is very high and can reach 60-70%. There is a gradient in the A*TREH allele frequencies in the small-numbered indigenous northern groups of Russia from the west (Khanty, Mansi, Nenets) to the east (peoples of the Far East). : The results are consistent with previously reported data on the higher carriage of the A*TREH mutant allele in Mongoloid populations compared to Caucasoid groups. It was hypothesized that, while the initial A*TREH allele prevalence in Mongoloid groups was moderately high, an adaptation to a low-sugar protein-lipid "high-latitude" diet led to a weaker control over the maintenance of the carriage of the ancestral G* allele. Trehalose malabsorption requires special attention of specialists in the field of nutrition, gastroenterology, public health, and medical genetics working in high-latitude regions.

Public Health Genetics: Surveying Preparedness for the Next Generation of Public Health Professionals.

Since the Human Genome Project's completion in 2003, the need for increased population genetic literacy has grown exponentially. To address this need, public health professionals must be educated appropriately to serve the public best. This study examines the current state of public health genetics education within existing master of public health (MPH) programs. A total of 171 MPH Council on Education for Public Health Accreditation (CEPH)-accredited programs across the nation were identified via a preliminary internet search. The American Public Health Association (APHA) Genomics Forum Policy Committee created 14 survey questions to assess the current status of incorporating genetics/genomics education within MPH programs. Using the Qualtrics survey system through the University of Pittsburgh, a link to the anonymous survey was sent to each director's email address obtained from their program's website. There were 41 survey responses, with 37 finished to completion, for a response rate of 21.6% (37/171). A total of 75.7% (28/37) of respondents reported having courses containing genetics/genomics information in their programs' coursework. Only 12.6% reported such coursework to be required for program completion. Commonly listed barriers to incorporating genetics/genomics include limited faculty knowledge and lack of space in existing courses and programs. Survey results revealed the incongruous and limited incorporation of genetics/genomics within the context of graduate-level public health education. While most recorded programs report offering public health genetics coursework, the extent and requirement of such instruction are not considered necessary for program completion, thereby potentially limiting the genetic literacy of the current pool of public health professionals.

Prevalence of trehalase enzymopathy genetic determinants in Siberian and Russian Far East populations

To date, it has been established that the patient's genotype plays a significant role in the formation of trehalase enzymopathy: the level of enzyme activity decreases when the G→A allele replacement occurs in the rs2276064 locus of the TREH gene. To assess the prevalence of trehalase deficiency, extensive population-based studies are needed. Clinical observations show that the reduced activity of bowel trehalase is more common in the Arctic than in European populations. The aim of this research was to analyze the frequency of the alleles and variants of trehalase gene (rs2276064 TREH) in the indigenous small-numbered populations of Siberia and the Russian Far East. Material and methods. Using the Infinium iSelect HD Custom BeadChip biochip on the iScan platform and real-time polymerase chain reaction on a Bio-Rad CFX96 Touch amplifier, genotyping of 1068 DNA samples was carried out, of which 711 represent 10 ethnic groups of the indigenous people of the North of Siberia and the Far East of the Russian Federation. Two reference groups of Russians (n=311) and Yakuts (n=46) represented the "Caucasoid" and "Mongoloid" poles of the Russian population. Results. The reduced trehalase activity that the heterozygous GA*TREH genotype determines can manifest itself in 19.8-53.7% of indigenous northerners. An additional 1.0 to 19.7% of the population are carriers of the AA*TREH genotype, which is associated with apparent trehalose malabsorption. The carriers may experience nausea, abdominal pain, and other dyspeptic symptoms after eating trehalose containing foods. The total risk of trehalase enzymopathy among the indigenous northerners in the Asian part of the Russian Federation is very high and can reach 60-70%. There is a gradient in the A*TREH allele frequencies in the small-numbered indigenous northern groups of Russia from the west (Khanty, Mansi, Nenets) to the east (peoples of the Far East). Conclusion. The results are consistent with previously reported data on the higher carriage of the A*TREH mutant allele in Mongoloid populations compared to Caucasoid groups. It was hypothesized that, while the initial A*TREH allele prevalence in Mongoloid groups was moderately high, an adaptation to a low-sugar protein-lipid "high-latitude" diet led to a weaker control over the maintenance of the carriage of the ancestral G allele. Trehalose malabsorption requires special attention of specialists in the field of nutrition, gastroenterology, public health, and medical genetics working in high-latitude regions.

Carrier detection probabilities for autosomal recessive variants in unrelated and consanguineous couples — an evaluation of the 86 genes of the ACMG ‘Tier 3’ panel

Carrier screening for autosomal recessive variants has become a cornerstone of community and public health genetics. While the first carrier screening programs were confined to conditions with relatively high prevalence, and hence well-known carrier frequency, the number of candidate genes has increased greatly since the advent of high-throughput DNA sequencing technologies. The epidemiological database of the ensuing gene panels is mostly sparse, and judgement of their performance is, therefore, anything but straightforward. We therefore derived estimates of the carrier detection probabilities among non-consanguineous and consanguineous couples as expected using the ‘Tier 3’ carrier screening gene panel recently recommended by the American College of Medical Genetics (ACMG). For non-Finnish Europeans, the respective estimate for unrelated couples equals 0.63%, implying that the ACMG Tier 3 panel accounts for over 90% of the genetic load for autosomal recessive diseases in this population. Among the offspring of first cousins, the corresponding incidence is expected to be tenfold higher, an increase still consistent with previous estimates of the overall risk of birth defects for this type of mating. Our considerations are intended to aid the implementation of carrier screening programs and to provide additional support to reproductive counselling and to obtaining informed consent.

Evaluating the Continued Integration of Genetics into Medical Sociology.

The 2010 special issue of Journal of Health and Social Behavior, titled "Fifty Years of Medical Sociology," defined the contours of the medical sociological perspective. We use this as a backdrop to outline and assess the continued integration of genetics into medical sociology research. We contend that the explosion of genetic and epigenetic data in population health data sources has made the medical sociological perspective increasingly relevant to researchers outside of sociology, including public health, epidemiology, and quantitative genetics. We describe vast, underappreciated, and mostly unsolved challenges that limit the scientifically appropriate interest in incorporating genetics into existing paradigms. It is our hope that medical sociologists continue this integration but redouble efforts to maintain the core insights in social science research, such as the importance of environmental and structural (i.e., nonbiological) factors in determining health processes and outcomes and the use of rich, integrated, and rigorous empirical analyses.

The sharing of research data facing the COVID-19 pandemic.

During the previous Ebola and Zika outbreaks, researchers shared their data, allowing many published epidemiological studies to be produced only from open research data, to speed up investigations and control of these infections. This study aims to evaluate the dissemination of the COVID-19 research data underlying scientific publications. Analysis of COVID-19 publications from December 1, 2019, to April 30, 2020, was conducted through the PubMed Central repository to evaluate the research data available through its publication as supplementary material or deposited in repositories. The PubMed Central search generated 5,905 records, of which 804 papers included complementary research data, especially as supplementary material (77.4%). The most productive journals were The New England Journal of Medicine, The Lancet and The Lancet Infectious Diseases, the most frequent keyword was pneumonia, and the most used repositories were GitHub and GenBank. An expected growth in the number of published articles following the course of the pandemics is confirmed in this work, while the underlying research data are only 13.6%. It can be deduced that data sharing is not a common practice, even in health emergencies, such as the present one. High-impact generalist journals have accounted for a large share of global publishing. The topics most often covered are related to epidemiological and public health concepts, genetics, virology and respiratory diseases, such as pneumonia. However, it is essential to interpret these data with caution following the evolution of publications and their funding in the coming months.

Βιοηθική και δημόσια υγεία: από τη δεκαετία 1970 στην πανδημία COVID-19

The strong relationship between bioethics and public health has been put forward since the early 1970s. The HIV/AIDS epidemic, erupted in the 1980s, serves as a catalyst for the broadening of the bioethics frameworks by the inclusion of ethical issues faced in public health. From the beginning of the 21st century, public health ethics has been emerged as a discipline and has been established as a subfield of bioethics.Topics in public health ethics include, among others, the public health research, the ethics and infectious disease control, the ethics of health promotion and disease prevention, the ethical issues in environmental and occupational health, the public health and health system reform: allocation of resources, access, priority setting, the international collaboration for global public health, the vulnerability and marginalized populations, the public health genetics, the public health genomics. The COVID-19 pandemic seems to constitute an area of conceptual and practical overlapping of all the above-mentioned topics and gives huge boost to research interest for public health bioethics.This paper explains the relationship between bioethics and public health through two time periods and, in particular, the “early” 1970s- 1990s era and the2000s & 2010s that is the period of the emergence and establishment of public health ethics marked, at the end, by the COVID-19 pandemic.

Genetics in Public Health

Genetics is considered a branch of science dealing with the study of heredity and variation in genes and genotype. A hybrid subspecialty of genetics and public health has come up in recent years. Public health genetics involves the application of genetics and molecular biotechnology in the improvement of community health and disease prevention. The Centers for Disease Control developed a framework comprising four essential public health functions and three critical issues associated with individual function. This review aims to highlight the integration of discoveries in genetic into public health. Scientific approach is required to study the impact of genetic discoveries on community health. Judicious assessment of the utility of genetic tests and development of standards and guidelines for reassuring superior genetic testing are critical steps in the process. Strong public health leadership to develop, implement, and evaluate disease intervention strategies is required for utilizing the advances in genetics for disease prevention. The critical issues that affect each function are partnerships and coordination; ethical, legal, and social issues; and education and training. An integrated and comprehensive scheme is required for the control of genetic diseases. Public health professionals shall help evolve, study, and propagate the scientific knowledge that would serve as a guide for public health action.

Эпидемиология наследственных болезней в практике здравоохранения: эволюция от теории к технологиям и наоборот

В настоящее время наиболее сильное изменение в области эпидемиологии наследственных болезней заключается в переходе от теоретических обобщений популяционной генетики к активному использованию молекулярно-генетических технологий в отношении тестирования отдельных индивидов. Это позволяет персонализировать оказание медицинской помощи, а также генерировать новые знания о грузе наследственных болезней в популяциях с их последующей трансляцией в практику здравоохранения. At the present time the most dramatic changes in the epidemiology of hereditary diseases is the transition from theoretical principles of population genetics in public health to the active use of molecular genetic technologies for individuals. Genetic discoveries are the basis of individualized medicine, as well as the source of new knowledge about the load of hereditary diseases in populations with their subsequent translation into healthcare system.

Developing a genetic services assessment tool to inform quality improvement efforts in state genetic service delivery

The Institute of Medicine recommended the utilization of metrics to improve quality in health care, although they have rarely been used in genetics. This study developed and tested a set of metrics for a quality assessment tool for genetic services METHODS: A systematic review of literature, guidelines, and consensus statements identified candidate measures for a possible assessment tool. An expert panel conducted a modified Delphi technique to rank the metrics. Ratings were computed to generate a score for each metric, creating a set of metrics for consensus discussions, pilot testing, and feasibility testing in eight Midwestern states. The panel reduced 61 candidate metrics to 21 for pilot testing in two states, which further limited and refined the set to 16 metrics. These 16 were categorized into five domains: service capacity, access to care, data systems, performance reporting, and workforce. Further feasibility testing in one Regional Genetics Collaborative identified the tool's usefulness and barriers to implementation. These quality metrics for both clinical and public health genetics across the lifespan may help medical professionals and policymakers evaluate quality and cost-effectiveness of genetic services on a statewide basis and stimulate outcome-oriented, health services research in medical genetics and genomics.

Laying Anchor: Inserting Precision Health into a Public Health Genetics Policy Course.

The United States Precision Medicine Initiative (PMI) was announced by then President Barack Obama in January 2015. It is a national effort designed to take into account genetic, environmental, and lifestyle differences in the development of individually tailored forms of treatment and prevention. This goal was implemented in March 2015 with the formation of an advisory committee working group to provide a framework for the proposed national research cohort of one million or more participants. The working group further held a public workshop on participant engagement and health equity, focusing on the design of an inclusive cohort, building public trust, and identifying active participant engagement features for the national cohort. Precision techniques offer medical and public health practitioners the opportunity to personally tailor preventive and therapeutic regimens based on informatics applied to large volume genotypic and phenotypic data. The PMI’s (All of Us Research Program’s) medical and public health promise, its balanced attention to technical and ethical issues, and its nuanced advisory structure made it a natural choice for inclusion in the University of Michigan course “Issues in Public Health Genetics” (HMP 517), offered each fall by the University’s School of Public Health. In 2015, the instructors included the PMI as the recurrent case study introduced at the beginning and referred to throughout the course, and as a class exercise allowing students to translate issues into policy. In 2016, an entire class session was devoted to precision medicine and precision public health. In this article, we examine the dialogues that transpired in these three course components, evaluate session impact on student ability to formulate PMI policy, and share our vision for next-generation courses dealing with precision health. Methodology: Class materials (class notes, oral exercise transcripts, class exercise written hand-ins) from the three course components were inspected and analyzed for issues and policy content. The purpose of the analysis was to assess the extent to which course components have enabled our students to formulate policy in the precision public health area. Analysis of student comments responding to questions posed during the initial case study comprised the initial or “pre-” categories. Analysis of student responses to the class exercise assignment, which included the same set of questions, formed the “post-” categories. Categories were validated by cross-comparison among the three authors, and inspected for frequency with which they appeared in student responses. Frequencies steered the selection of illustrative quotations, revealing the extent to which students were able to convert issue areas into actual policies. Lecture content and student comments in the precision health didactic session were inspected for degree to which they reinforced and extended the derived categories. Results: The case study inspection yielded four overarching categories: (1) assurance (access, equity, disparities); (2) participation (involvement, representativeness); (3) ethics (consent, privacy, benefit sharing); and (4) treatment of people (stigmatization, discrimination). Class exercise inspection and analysis yielded three additional categories: (5) financial; (6) educational; and (7) trust-building. The first three categories exceeded the others in terms of number of student mentions (8–14 vs. 4–6 mentions). Three other categories were considered and excluded because of infrequent mention. Students suggested several means of trust-building, including PMI personnel working with community leaders, stakeholder consultation, networking, and use of social media. Student representatives prioritized participant and research institution access to PMI information over commercial access. Multiple schemes were proposed for participant consent and return of results. Both pricing policy and Medicaid coverage were touched on. During the didactic session, students commented on the importance of provider training in precision health. Course evaluation highlighted the need for clarity on the organizations involved in the PMI, and leaving time for student-student interaction. Conclusions: While some student responses during the exercise were terse, an evolution was detectable over the three course components in student ability to suggest tangible policies and steps for implementation. Students also gained surety in presenting policy positions to a peer audience. Students came up with some very creative suggestions, such as use of an electronic platform to assure participant involvement in the disposition of their biological sample and personal health information, and alternate examples of ways to manage large volumes of data. An examination of socio-ethical issues and policies can strengthen student understanding of the directions the Precision Medicine Initiative is taking, and aid in training for the application of more varied precision medicine and public health techniques, such as tier 1 genetic testing and whole genome and exome sequencing. Future course development may reflect additional features of the ongoing All of Us Research Program, and further articulate precision public health approaches applying to populations as opposed to single individuals.

Proposed outcomes measures for state public health genomic programs.

Purpose:To assess the implementation of evidence-based genomic medicine and its population-level impact on health outcomes and to promote public health genetics interventions, in 2015 the National Academy of Sciences, Engineering, and Medicine formed an action collaborative, the Genomics and Public Health Action Collaborative (GPHAC). This group engaged key stakeholders from public/population health agencies, along with experts in the fields of health disparities, health literacy, implementation science, medical genetics, and patient advocacy.Methods:In this paper, we present the efforts to identify performance objectives and outcome metrics. Specific attention is placed on measures related to Hereditary Breast Ovarian Cancer (HBOC) syndrome and Lynch syndrome (LS), two conditions with existing evidence-based genomic applications that can have immediate impact on morbidity and mortality.Conclusion:Evidence-based public health requires outcome metrics yet few exist for genomics. Therefore, we have proposed performance objectives that states might use and provided examples of a few state level activities already underway, that are designed to collect outcome measures for HBOC and LS.

Creating a Healthier Nation through Public Health Genetics

Creating a Healthier Nation through Public Health Genetics

Genome-based newborn screening: a conceptual analysis of the best interests of the child standard.

Advances in genome-based sequencing technologies now allows for numerous genes to be analyzed in a single test, compared with previous gene-by-gene approaches [1]. While genome-based sequencing is gradually integrated into clinical care, there is also a strong push to use these technologies in public health settings [2–4], such as newborn screening programs [2,5]. In line with this interest, the US NIH recently invested US$25 million to study the medical and ethical implications of genomebased sequencing of newborns, although the plethora of issues this might pose are well recognized [6–7]. One issue relates to the paradigm shift in public health programs this use of genomic sequencing would create [6–8]. Since their introduction in the 1960s, the focus of newborn screening programs has been the identification of asymptomatic newborns with rare metabolic disorders, to allow timely interventions that significantly decrease morbidity and mortality. As the best interests of the child (BIC) was the core principle [8], selection of conditions was limited to those where newborns left untreated would suffer from severe illnesses, and early intervention carried definitive medical benefit [9]. In certain regions, the progressive use of new screening technologies has historically led to relaxing of the traditional criteria to screen only for early-onset, treatable conditions [10]. As a result, screening programs have occasionally shifted away from using the BIC as the primary consideration to justify inclusion of conditions in the screening panel. In addition, the nature of the information provided through genome-based newborn screening poses additional hurdles for determining what is within the scope of the BIC at individual, familial and populational levels and the appropriateness of the BIC argument in the newborn screening setting. This article therefore discusses the legal concept of BIC at a theoretical level.

An integrative model of inter- and intragenerational preconception processes influencing birthweight in the United States.

Social inequalities in birthweight are an important population health concern as low birthweight is one mechanism through which inequalities are reproduced across generations. Yet, we do not understand what causes these social inequalities. This study draws together theoretic and empiric findings from disparate disciplines--sociology, economics, public health, and behavior genetics--to develop a new integrative intra- and intergenerational model of preconception processes influencing birthweight. This model is empirically tested using structural equation modeling and population-level data containing linked mother-daughter pairs from the National Longitudinal Survey of Youth (NLSY79) and the Children of the NLSY79 (N = 1,580 mother-daughter pairs). Results reveal that birthweight is shaped by preconception factors dating back to women's early life environment as well as conditions dating back three generations, via integrative intra- and intergenerational processes. These processes reveal specific pathways through which social inequality can transmit from mothers to children via birthweight.

Introduction to the Special Issue: Public Health Genetics and Genomics.

This special issue of the Journal of Genetic Counseling is dedicated to public health genetics and genomics. The seventeen papers featured in this issue span such topics as genetic counselors in public health roles, newborn screening, population screening, ethics, and health beliefs and behaviors. In this introduction to the special issue, we review some history of public health genetics and genomics, present the Centers for Disease Control and Prevention's "10 Essential Public Health Services" with associated genetics specific recommendations and priorities, and briefly overview how each article ties into the world of public health genetics and genomics. We hope this issue encourages genetic counselors to visualize their ever expanding and important roles in public health genetics and genomics, as well as their contributions to improving population health.

Novel variation and de novo mutation rates in population-wide de novo assembled Danish trios.

Building a population-specific catalogue of single nucleotide variants (SNVs), indels and structural variants (SVs) with frequencies, termed a national pan-genome, is critical for further advancing clinical and public health genetics in large cohorts. Here we report a Danish pan-genome obtained from sequencing 10 trios to high depth (50 × ). We report 536k novel SNVs and 283k novel short indels from mapping approaches and develop a population-wide de novo assembly approach to identify 132k novel indels larger than 10 nucleotides with low false discovery rates. We identify a higher proportion of indels and SVs than previous efforts showing the merits of high coverage and de novo assembly approaches. In addition, we use trio information to identify de novo mutations and use a probabilistic method to provide direct estimates of 1.27e−8 and 1.5e−9 per nucleotide per generation for SNVs and indels, respectively.

Public health genetic counselors: activities, skills, and sources of learning.

Specialization within genetic counseling is apparent, with 29 primary specialties listed in the National Society of Genetic Counselors' 2012 Professional Status Survey (PSS). PSS results show a steady proportion of genetic counselors primarily involved in public health, yet do not identify all those performing public health activities. Little is known about the skills needed to perform activities outside of "traditional" genetic counselor roles and the expertise needed to execute those skills. This study aimed to identify genetic counselors engaging in public health activities, the skills used, and the most influential sources of learning for those skills. Participants (N = 155) reported involvement in several public health categories: (a) Education of Public and/or Health Care Providers (n = 80, 52 %), (b) Population-Based Screening Programs (n = 70, 45 %), (c) Lobbying/Public Policy (n = 62, 40 %), (d) Public Health Related Research (n = 47, 30 %), and (e) State Chronic Disease Programs (n = 12, 8 %). Regardless of category, "on the job" was the most common primary source of learning. Genetic counseling training program was the most common secondary source of learning. Results indicate that the number of genetic counselors performing public health activities is likely higher than PSS reports, and that those who may not consider themselves "public health genetic counselors" do participate in public health activities. Genetic counselors learn a diverse skill set in their training programs; some skills are directly applicable to public health genetics, while other public health skills require additional training and/or knowledge.

Rethinking Our Public Health Genetics Research Paradigm

Since the sequencing of the human genome, tremendous resources have been dedicated to understanding how genetic determinants may drive the production of disease. Despite some successes, the promise of genetics research in these areas remains largely unrealized. The focus on isolating individual (or clusters of) genes that may be associated with narrowly defined phenotypes in large part explains this discrepancy. In particular, efforts to identify genotypes associated with narrow phenotypes force the field to use study designs that capitalize on homogeneous samples to minimize the potential for competing influences or confounders, which imposes important limitations on understanding the role of genes in human health. We argue that a population health genetics that incorporates genetics into large, multiwave, multilevel cohorts has the best potential to clarify how genes, in combination and with the environment, jointly influence population health.

Timmermans, S. and Buchbinder, M.Saving Babies? The Consequences of Newborn Genetic Screening, Chicago: University of Chicago Press. 2013. 307pp. £19.50 (hbk) ISBN: 978‐0‐226‐92497‐7

Timmermans, S. and Buchbinder, M.Saving Babies? The Consequences of Newborn Genetic Screening, Chicago: University of Chicago Press. 2013. 307pp. £19.50 (hbk) ISBN: 978‐0‐226‐92497‐7