Ethnic difference in osteoporosis-related phenotypes and its potential underlying genetic determination

Osteoporosis is a serious health problem in both Caucasians and Asians. Caucasians and Asians are two distinct major ethnic groups, which may have differential genetic determination underlying complex genetic diseases such as osteoporosis. However, to date, there has been no systematic review focusing on the aspect of ethnic difference in risk to osteoporosis and its potential underlying genetic determination between Asians and Caucasians. Here, we firstly review diverse aspects of osteoporosis-related differences, including the differences of epidemiology of osteoporotic fractures, peak bone mass, bone loss, bone area, bone geometry and drug treatment response between Asians and Caucasians. Then, we provide some potential genetic evidence on the different heritability and inheritance mode of bone phenotypes, the different osteoporosis candidate genes and the differential results in related molecular studies between them, to explain the above osteoporosis-related phenotypic differences. The results suggest that the osteoporosis-related phenotypic differences between Asians and Caucasians may be partially the result of the different ethnic genetic background. The present review may increase our understanding of potential different mechanisms related to ethnicity in pathogenesis of osteoporosis for effective and potentially customized treatments in different major ethnic groups.     

Mainstreaming Sex and Gender Analysis in Public Health Genomics

BackgroundThe integration of genome-based knowledge into public health or public health genomics (PHG) aims to contribute to disease prevention, health promotion, and risk reduction associated with genetic disease susceptibility. Men and women differ, for instance, in susceptibilities for heart disease, obesity, or depression due to biologic (sex) and sociocultural (gender) factors and their interaction. Genome-based knowledge is rapidly increasing, but sex and gender issues are often not explored.ObjectiveTo explore the implications of a sex and gender analysis for PHG.MethodsWe explore genome-based knowledge in relation to sex and gender aspects using depression as an example, gender equality, and the intersection of sex and gender with other social stratifiers such as ethnic background or socioeconomic status.ResultsWe advocate a sex- and gender-sensitive genomics research agenda alongside studies that provide sex-disaggregated data rather than controls based on sex. Such a research agenda is needed to guide research on how genomics is understood and perceived by men and women across groups, and for the equitable and responsible translation of such knowledge into the public health domain.ConclusionsIncluding sex and gender analysis in PHG research will not only shed more light on phenomena such as diseases with a higher prevalence in either men or women, but will ultimately lead to gendered innovations by way of exploring how gendered and cultural environments increase or safeguard genetic predispositions.     

Leveraging genetic ancestry to study health disparities

Research to understand human genomic variation and its implications in health has great potential to contribute in the reduction of health disparities. Biological anthropology can play important roles in genomics and health disparities research using a biocultural approach. This paper argues that racial/ethnic categories should not be used as a surrogate for sociocultural factors or global genomic clusters in biomedical research or clinical settings, because of the high genetic heterogeneity that exists within traditional racial/ethnic groups. Genetic ancestry is used to show variation in ancestral genomic contributions to recently admixed populations in the United States, such as African Americans and Hispanic/Latino Americans. Genetic ancestry estimates are also used to examine the relationship between ancestry-related biological and sociocultural factors affecting health disparities. To localize areas of genomes that contribute to health disparities, admixture mapping and genome-wide association studies (GWAS) are often used. Recent GWAS have identified many genetic variants that are highly differentiated among human populations that are associated with disease risk. Some of these are population-specific variants. Many of these variants may impact disease risk and help explain a portion of the difference in disease burden among racial/ethnic groups. Genetic ancestry is also of particular interest in precision medicine and disparities in drug efficacy and outcomes. By using genetic ancestry, we can learn about potential biological differences that may contribute to the heterogeneity observed across self-reported racial groups.     

Precision wildlife medicine: applications of the human‐centred precision medicine revolution to species conservation

The current species extinction crisis is being exacerbated by an increased rate of emergence of epizootic disease. Human‐induced factors including habitat degradation, loss of biodiversity and wildlife population reductions resulting in reduced genetic variation are accelerating disease emergence. Novel, efficient and effective approaches are required to combat these epizootic events. Here, we present the case for the application of human precision medicine approaches to wildlife medicine in order to enhance species conservation efforts. We consider how the precision medicine revolution, coupled with the advances made in genomics, may provide a powerful and feasible approach to identifying and treating wildlife diseases in a targeted, effective and streamlined manner. A number of case studies of threatened species are presented which demonstrate the applicability of precision medicine to wildlife conservation, including sea turtles, amphibians and Tasmanian devils. These examples show how species conservation could be improved by using precision medicine techniques to determine novel treatments and management strategies for the specific medical conditions hampering efforts to restore population levels. Additionally, a precision medicine approach to wildlife health has in turn the potential to provide deeper insights into human health and the possibility of stemming and alleviating the impacts of zoonotic diseases. The integration of the currently emerging Precision Medicine Initiative with the concepts of EcoHealth (aiming for sustainable health of people, animals and ecosystems through transdisciplinary action research) and One Health (recognizing the intimate connection of humans, animal and ecosystem health and addressing a wide range of risks at the animal–human–ecosystem interface through a coordinated, collaborative, interdisciplinary approach) has great potential to deliver a deeper and broader interdisciplinary‐based understanding of both wildlife and human diseases.     

Harnessing Nutrigenomics: Development of web-based communication, databases, resources, and tools

Nutrient - gene interactions are responsible for maintaining health and preventing or delaying disease. Unbalanced diets for a given genotype lead to chronic diseases such as obesity, diabetes, cardiovascular, and are likely to contribute to increased severity and/or early-onset of many age-related diseases. Many nutrition and many genetic studies still fail to properly include both variables in the design, execution, and analyses of human, laboratory animal, or cell culture experiments. The complexity ofnutrient-gene interactions has led to the realization that strategic international alliances are needed to improve the completeness of nutrigenomic studies - a task beyond the capabilities of a single laboratory team. Eighty-eight researchers from 22 countries recently outlined the issues and challenges for harnessing the nutritional genomics for public and personal health. The next step in the process of forming productive international alliances is the development of a virtual center for organizing collaborations and communications that foster resources sharing, best practices improvements, and creation of databases. We describe here plans and initial efforts of creating the Nutrigenomics Information Portal, a web-based resource for the international nutrigenomics society. This portal aims at becoming the prime source ofinformation and interaction for nutrigenomics scientists through a collaborative effort.     

Genomic Studies of Hereditary Disorders and the Genetic Diversity of Siberian Populations

The review considers the results of genome research on the Russian program Human Genome carried out in the Institute of Medical Genetics (Tomsk) since 1990. The three major fields were molecular cytogenetics and chromosomal disorders, genomics of Mendelian and common diseases, and ethnogenomics of the North Asian population. Several human genes were cytogenetically mapped, and numerical and structural abnormalities associated with human diseases were studied by fluorescence hybridization. Procedures of DNA diagnosis were developed for 15 hereditary diseases. New data were obtained on the genetic heterogeneity of idiopathic hypertrophic cardiomyopathy. The genetic bases of multifactorial (atopic bronchial asthma) and infectious (tuberculosis) diseases were analyzed. The North Eurasian population (41 local populations of 21 ethnic groups) was tested for genetic diversity with numerous genetic markers, including Y-chromosomal haplotypes, autosomal microsatellites, and polymorphic Alu insertions.     

Genomic study of the hereditary pathology and genetic diversity of the Siberian population

The review considers the results of genome research on the Russian program Human Genome carried out in the Institute of Medical Genetics (Tomsk) from 1990. The three major fields were molecular cytogenetics and chromosomal disorders, genomics of Mendelian and high-incidence diseases, and ethnogenomics of the North Asian population. Several human genes were cytogenetically mapped, and numerical and structural abnormalities associated with human diseases studied by fluorescence hybridization. Procedures of DNA diagnostics were developed for 15 hereditary diseases. New data were obtained on genetic heterogeneity of idiopathic hypertrophic cardiomyopathy. The genetic bases of multifactorial (atopic bronchial asthma) and infectious (tuberculosis) diseases were analyzed. The North Eurasian population (41 local populations of 21 ethnic groups) was tested for genetic diversity with numerous genetic markers, including Y-chromosomal haplotypes, autosomal microsatellites, and polymorphic Alu insertions.     

The politics of genealogical incorporation: ethnic difference,genetic relatedness and national belonging*

This paper explores the relationship between genomic accounts of ethnic origins and distinctiveness and genealogical models of ethnic and national similarity and difference. It does so by focusing on genetic investigations of Irish Traveller origins in the context of ongoing campaigns for state recognition of Irish Travellers as an ethnic group, and in relation to the politics of national belonging. The ostensibly ethical practice of liberal genomics is entangled with the fraught politics of the Irish state’s commitments to addressing ethnic minority rights, insistence on differentiating between Travellers and other ethnic groups on the basis of genealogical difference, and the genealogical incorporation of Travellers within the national community of shared descent. Though ideas of ancestral relatedness across social or cultural boundaries are often figured as politically progressive, locating groups within a national family tree on the basis of genealogical relatedness can simultaneously deny ethnic difference and naturalize exclusive models of nationhood.     

Prevalences of hereditary diseases in different populations of Russia

The geographic distribution of hereditary diseases (HDs) in different populations and ethnic groups of Russia has been studied. The main patterns of the formation of the prevalence and spectrum of HDs in five ethnic groups (Russians from six regions, Mari, Chuvashes, Udmurts, and Adygeans) from a total of ten regions of Russia have been analyzed. Analysis of correlations suggests that genetic drift is the main factor of the genetic differentiation of populations with respect to the prevalence of HDs. Accumulation of HDs in individual populations and ethnic groups has been analyzed. Hereditary diseases characterized by locally high prevalence rates in individual populations or ethnic groups have been detected. The main patterns of the accumulation of individual diseases and differences between populations and ethnic groups in this respect have been studied with the use of principal component analysis, which describes these patterns more graphically. It has been demonstrated that the genes of HDs are a promising tool for characterizing ethnogenetic processes in populations.     

Prevalences of hereditary diseases in various populations in Russia

The geographic distribution of hereditary diseases (HDs) in different populations and ethnic groups of Russia has been studied. The main patterns of the formation of the prevalence and spectrum of HDs in five ethnic groups (Russians from six regions, Mari, Chuvashes, Udmurts, and Adygeans) from a total of ten regions of Russia have been analyzed. Analysis of correlations suggests that genetic drift is the main factor of the genetic differentiation of populations with respect to the prevalence of HDs. Accumulation of HDs in individual populations and ethnic groups has been analyzed. Hereditary diseases characterized by locally high prevalence rates in individual populations or ethnic groups have been detected. The main patterns of the accumulation of individual diseases and differences between populations and ethnic groups in this respect have been studied with the use of principal component analysis, which describes these patterns more graphically. It has been demonstrated that the genes of HDs are a promising tool for characterizing ethnogenetic processes in populations.     

Reflections on the Surgeon General's Report on Mental Health,Culture, Race,and Ethnicity

The main goal of this paper is to evaluate the Supplement to the Surgeon General's Report on Mental Health, with an eye toward informing future efforts to prevent and treat mental illness among racial and ethnic minorities. I first briefly discuss the historical background of the Supplement. I then present its strengths, which include the authority and visibility of the Office of the Surgeon General, the organization of the report by racial/ethnic group, the examination of the social and historical context of each of the racial/ethnic groups, and the emphasis on science. Last, I identify three major tensions within the Supplement, focusing on groups versus cultural processes, situating culture within individuals or social worlds, and examining differences between minority groups and whites versus examining conceptually informed processes. The Supplement makes a significant contribution to advancing our understanding of the mental health of racial and ethnic minority groups. The actions that follow (or don't follow), however, will determine the import of this document.     

Post‐GWAS in Psychiatric Genetics: A Developmental Perspective on the “Other” Next Steps

As psychiatric genetics enters an era where gene identification is finally yielding robust, replicable genetic associations and polygenic risk scores, it is important to consider next steps and delineate how that knowledge will be applied to ultimately ameliorate suffering associated with substance use and psychiatric disorders. Much of the post‐genome‐wide association study discussion has focused on the potential of genetic information to elucidate the underlying biology and use this information for the development of more effective pharmaceutical treatments. In this review we focus on additional areas of research that should follow gene identification. By taking genetic findings into longitudinal, developmental studies, we can map the pathways by which genetic risk manifests across development, elucidating the early behavioral manifestations of risk, and studying how various environments and interventions moderate that risk across developmental stages. The delineation of risk across development will advance our understanding of mechanism, sex differences and risk and resilience processes in different racial/ethnic groups. Here, we review how the extant twin study literature can be used to guide these efforts. Together, these new lines of research will enable us to develop more informed, tailored prevention and intervention efforts.     

Dissecting complex phenotypes using the genomics of twins

Genetics in the post-genomic period is shifting from structural to functional genetics or genomics. Meanwhile, the use of twins is largely expanding from traditional heritability estimation for disease phenotypes to the study of both diseases and various molecular phenotypes, such as the regulatory phenotypes in functional genomics concerning gene expression and regulation, by engaging both classical twin design and marker-based gene mapping techniques in genetic epidemiology. New research designs have been proposed for making novel uses of twins in studying the molecular basis in the epigenetics of human diseases. Besides, twins not only serve as ideal samples for disease gene mapping using conventional genetic markers but also represent an excellent model for associating DNA copy number variations, a structural genetic marker, with human diseases. It is believed that, with the rapid development in biotechniques and new advances in bioinformatics, the unique samples of twins will make new contributions to our understanding of the nature and nurture in complex disease development and in human health. This paper aims at summarizing the new uses of twins in current genetic studies and suggesting novel proposes together with useful design and analytical strategies.     

Karma, reincarnation, and medicine: Hindu perspectives on biomedical research

Prior to the completion of the Human Genome Project, bioethicists and other academics debated the impact of this new genetic information on medicine, health care, group identification, and peoples’ lives. A major issue is the potential for unintended and intended adverse consequences to groups and individuals. When conducting research in, for instance, American Indian and Alaskan native (AI/AN) populations, political, cultural, religious and historical issues must be considered. Among African Americans, the Tuskegee Syphilis Experiment is a reminder of racism and discrimination in this country. The goal of the current study is to understand reasons for participating, or not, in genetic research such as the HapMap project and other genetic/medical research from the perspective of the Indian American community in Houston, Texas. In this article, we report on a topic central to this discussion among Indian Americans: karma and reincarnation. Both concepts are important beliefs when considering the body and what should happen to it. Karma and reincarnation are also important considerations in participation in medical and genetic research because, according to karma, what is done to the body can affect future existences and the health of future descendants. Such views of genetic and medical research are culturally mediated. Spiritual beliefs about the body, tissue, and fluids and what happens to them when separated from the body can influence ideas about the utility and acceptability of genetic research and thereby affect the recruitment process. Within this community it is understood that genetic and environmental factors contribute to complex diseases such as diabetes, hypertension, and cancer; and acknowledgment of the significance of environmental stressors in the production of disease. A commitment to service, i.e. “betterment of humanity,” karmic beliefs, and targeting environmental stressors could be prominent avenues for public health campaigns in this population. This study suggests that minority status does not automatically indicate unwillingness to participate in genetic or medical research. Indian Americans were not skeptical about the potential benefits of biomedical research in comparison to other ethnic minority communities in the United States.     

Variations on a Chip: Technologies of Difference in Human Genetics Research

In this article we examine the history of the production of microarray technologies and their role in constructing and operationalizing views of human genetic difference in contemporary genomics. Rather than the “turn to difference” emerging as a post-Human Genome Project (HGP) phenomenon, interest in individual and group differences was a central, motivating concept in human genetics throughout the twentieth century. This interest was entwined with efforts to develop polymorphic “genetic markers” for studying human traits and diseases. We trace the technological, methodological and conceptual strategies in the late twentieth century that established single nucleotide polymorphisms (SNPs) as key focal points for locating difference in the genome. By embedding SNPs in microarrays, researchers created a technology that they used to catalog and assess human genetic variation. In the process of making genetic markers and array-based technologies to track variation, scientists also made commitments to ways of describing, cataloging and “knowing” human genetic differences that refracted difference through a continental geographic lens. We show how difference came to matter in both senses of the term: difference was made salient to, and inscribed on, genetic matter(s), as a result of the decisions, assessments and choices of collaborative and hybrid research collectives in medical genomics research.     

Ethnic differences in atherosclerosis, cardiovascular disease and lipid metabolism

PURPOSE OF REVIEW: Comparison of risk factors and cardiovascular disease among racial and ethnic groups is a powerful approach to study genetics and lifestyle, or environmental interactions. RECENT FINDINGS: Most, mean or median, cardiovascular risk factor levels are similar among black and white people. There are much greater differences in the distribution of risk factor level within a specific race and ethnic group than between US populations. There are also very large differences in levels of risk factors for coronary heart disease between specific ethnic migrant populations such as comparing black people in Africa with those in the US, or Japanese people in Japan with those in Hawaii and California. Differences in distribution of risk factors and disease between race and ethnic group are a function of the frequency of specific genotypes and interaction with environmental factors. Several of the most important differences between racial groups are higher blood pressure, lower triglycerides and higher HDL cholesterol among blacks, higher prevalence of diabetes and insulin resistance among Mexican Americans and American Indians, and higher triglyceride levels among the Japanese. SUMMARY: Further studies of racial and ethnic differences should focus on unique phenotypes and genotypic differences, international and migrant studies and large enough sample sizes to provide robust results. The sprinkling of a percentage of minority participants in each study is worthless. The study of racial and ethnic differences in disease and detection of risk factor levels must be based on solid hypotheses that can evaluate the interaction of lifestyle and possible genetic attributes. Many of the reported ethnic differences in risk factors and disease in US populations are primarily a function of differences in education, socioeconomic variations, and utilization of preventive and clinical treatments.     

Limitations of the human reference genome for personalized genomics

Data from the 1000 genomes project (1KGP) and Complete Genomics (CG) have dramatically increased the numbers of known genetic variants and challenge several assumptions about the reference genome and its uses in both clinical and research settings. Specifically, 34% of published array-based GWAS studies for a variety of diseases utilize probes that overlap unanticipated single nucleotide polymorphisms (SNPs), indels, or structural variants. Linkage disequilibrium (LD) block length depends on the numbers of markers used, and the mean LD block size decreases from 16 kb to 7 kb,when HapMap-based calculations are compared to blocks computed from1KGP data. Additionally, when 1KGP and CG variants are compared, 19% of the single nucleotide variants (SNVs) reported from common genomes are unique to one dataset; likely a result of differences in data collection methodology, alignment of reads to the reference genome, and variant-calling algorithms. Together these observations indicate that current research resources and informatics methods do not adequately account for the high level of variation that already exists in the human population and significant efforts are needed to create resources that can accurately assess personal genomics for health, disease, and predict treatment outcomes.     

DEVELOPMENTAL STABILITY, DISEASE AND MEDICINE

Developmental stability reflects the ability of a genotype to undergo stable development of a phenotype under given environmental conditions. Deviations from developmental stability arise from the disruptive effects of a wide range of environmental and genetic stresses, and such deviations are usually measured in terms of fluctuating asymmetry and phenodeviants. Fluctuating asymmetry is the most sensitive indicator of the ability to cope with stresses during ontogeny. There is considerable evidence that developmental stability, and especially fluctuating asymmetry, is a useful measure of phenotypic and genetic quality, because it covaries negatively with performance in multiple fitness domains in many species, including humans. It is proposed that developmental stability is an important marker of human health. Our goal is to initiate formally the integration of the sciences of evolutionary biology, developmental biology and medicine. We believe that this integrative framework provides a significant addition to the growing field of Darwinian medicine. The literature linking developmental stability and disease in humans is reviewed. Recent biological theoretical treatments pertaining to developmental stability are applied to a range of human health issues such as genetic diseases, ageing and survival, subfertility, abortion, child maltreatment by parents, cancer, infectious diseases, physiological and mental health, and physical attractiveness as a health certification.