Molecular genetics of Alzheimer's disease

Genetic factors are involved in the aetiology of Alzheimer's disease (AD) in 25–40% of the cases. In some cases AD clearly segregates as an autosomal dominant trait in families. Three genes have been identified which, when mutated, cause AD: the Aβ amyloid precursor protein gene (APT), and the presenilin-1 (PSEN1) and presenilin-2 (PSEN2) genes. Together, these mutations are responsible for 30–50% of the cases with autosomal dominant AD, and for about 5% of AD in general. In cases where the inheritance pattern is unclear and in sporadic cases the ?4 allele of the apolipoprotein E gene (APOE) has been identified as a major risk factor contributing to the pathogenesis of AD in about 20% of the cases. Although mutations in the known genes are a rare cause of AD they are useful for the purposes of presymptomatic diagnostics in autosomal dominant AD families that segregate these mutations. Also, the identification of these genes and mutations has been extremely important to the recent evolution in the understanding of the biology of the disease. However, other causative and risk genes are involved in AD and need to be identified in order to fully elucidate the biology of AD. This will ultimately lead to the development of effective therapies for this major disease.     

Building an Ontology for Identity Resolution in Healthcare and Public Health

Integration of disparate information from electronic health records, clinical data warehouses, birth certificate registries and other public health information systems offers great potential for clinical care, public health practice, and research. Such integration, however, depends on correctly matching patient-specific records using demographic identifiers. Without standards for these identifiers, record linkage is complicated by issues of structural and semantic heterogeneity.Objectives: Our objectives were to develop and validate an ontology to: 1) identify components of identity and events subsequent to birth that result in creation, change, or sharing of identity information; 2) develop an ontology to facilitate data integration from multiple healthcare and public health sources; and 3) validate the ontology’s ability to model identity-changing events over time.Methods: We interviewed domain experts in area hospitals and public health programs and developed process models describing the creation and transmission of identity information among various organizations for activities subsequent to a birth event. We searched for existing relevant ontologies. We validated the content of our ontology with simulated identity information conforming to scenarios identified in our process models.Results: We chose the Simple Event Model (SEM) to describe events in early childhood and integrated the Clinical Element Model (CEM) for demographic information. We demonstrated the ability of the combined SEM-CEM ontology to model identity events over time.Conclusion: The use of an ontology can overcome issues of semantic and syntactic heterogeneity to facilitate record linkage.     

Molecular genetics of anxiety in mice and men

Human anxiety disorders represent one of the most common mental illnesses. They are complex diseases with both genetic and environmental factors affecting their predisposition. Since the basic neuronal mechanisms are shared across mammalian species, the same set of genes may regulate critical aspects of anxiety in humans and in lower species. In this review, we first summarize findings from human molecular genetic approaches to anxiety disorders or anxiety‐related personality traits: genome‐wide scans and candidate gene studies in large families or case‐control cohorts. We then discuss recent studies that have used genome‐wide methods in mouse strains to identify genes that regulate anxiety‐like behavior. Although it has been difficult to pinpoint specific susceptibility genes for anxiety disorders, ongoing efforts to collect larger study cohorts and to develop new genetic tools should help in this task. Studies in animals have shown that novel quantitative trait locus (QTL) and functional genomics approaches might lead to the identification of regulators of anxiety in mice, and that these genes can be tested for their involvement in human anxiety disorders. Finally, breakthroughs are expected in the fine‐mapping of human and mouse genetic linkage regions and in the identification of novel candidate genes using genome‐wide methods in mouse models of anxiety.     

The genetics of osteoarthritis

The study of the etiology of osteoarthritis (OA) is distinguished by a long-standing consideration of the disease as an inherited disorder. Until the last decade, the study of OA as a genetic disease was limited to anecdotal reports of families in which specific OA traits were clustered. The impetus to further explore the genetics of OA has come from our increasing understanding of the nature of complex genetic disease in which disease traits need not be inherited in a Mendelian manner. This review will acquaint the reader with the impressive and fast-paced progress that has been made, especially in the past decade, regarding the study of OA as a heritable disease. While this review is not meant to be an exhaustive compendium of every published study, it will familiarize the reader with some of the highlights of OA genetics, as well as illustrate the range and depth of effort needed to unravel of genetics of complex diseases, such as OA.     

Vaccine-preventable disease-related hospitalization among immigrants and refugees to Canada: Study of linked population-based databases

While immigrants tend to be healthier especially when they first arrived, this healthy immigrant effect may not apply to vaccine-preventable diseases (VPD) especially among immigrants from countries without vaccination programs. There is therefore an important information gap regarding differential health outcome and hospitalization usage by immigrant status, landing cohort, world region and immigrant category. This study focused on acute-care hospitalization, and used two recently linked population-based databases in Canada, namely, the 2006 Census linked to the Hospital Discharge Abstract (DAD), and the Immigrant Landing File linked to the DAD (ILF-DAD) to estimate crude and age-standardized VPD-related hospitalization rates (ASHR) by the above-mentioned immigrant characteristics to be compared with that for overall Canadian-born reference population. Based on the 2006 Census-DAD linked database, VPD-specific ASHR for overall immigrants was significantly higher than that for the Canadian-born population (1.6, 95% CI, 1.5, 1.6 vs 1.2, 95% CI, 1.1, 1.2, respectively). VPD-specific ASHRs by landing cohorts also increased with years in Canada (e.g. 1.4, 95% CI, 1.3, 1.5 for the 1990–2006 cohort, and 1.6, 95% CI, 1.5, 1.7 for the pre-1980 cohort). Based on the 1980–2006 ILF-DAD, the VPD-specific ASHRs were highest among Southeast and East Asians (e.g. 2.1, 95% CI, 1.9, 2.3 for East Asia). Compared with the Canadian-born, economic class immigrants overall had significantly lower ASHR (1.4, 95% CI 1.2, 1.6), but the low rate was mainly due to the dependants (spouse or children) within this class (0.8, 95% CI 0.6, 1.1). Both family and refugee categories had significantly higher ASHRs (1.3, 95% CI, 1.2, 1.5 and 1.7, 95% CI, 1.4, 2.1, respectively), especially among those refugees assisted by government (2.0, 95% CI, 1.4, 2.6). With increasing immigration, changing source countries and emerging needs for refugee settlements in Canada, these newly linked datasets help to monitor VPD-related hospitalization pattern among Canadian immigrants.     

“Whose data is it anyway?” The implications of putting small area-level health and social data online

Data from electronic patient management systems, routine national health databases, and social administrative systems have increased significantly over the past decade. These data are increasingly used to create maps and analyses communicating the geography of health and illness. The results of these analyses can be easily disseminated on the web often without due consideration for the identification, access, ethics, or governance, of these potentially sensitive data. Lack of consideration is currently proving a deterrent to many organisations that might otherwise provide data to central repositories for invaluable social science and medical research. We believe that exploitation of such data is needed to further our understanding of the determinants of health and inequalities. Therefore, we propose a geographical privacy-access continuum framework, which could guide data custodians in the efficient dissemination of data while retaining the confidentiality of the patients/individuals concerned. We conclude that a balance of restriction and access is needed allowing linkage of multiple datasets without disclosure, enabling researchers to gather the necessary evidence supporting policy changes or complex environmental and behavioural health interventions.