The completion of the Human Genome Project has increased the pace of discovery of genetic markers for disease. Despite tremendous efforts in fundamental research, clinical applications still lag behind expectations, partly due to the lack... more
The completion of the Human Genome Project has increased the pace of discovery of genetic markers for disease. Despite tremendous efforts in fundamental research, clinical applications still lag behind expectations, partly due to the lack of effective tools to systematically search for and summarize published data relative to the clinical assessment of new diagnostic molecular tests. Through a collaborative process using published tools and an expert panel, we developed a detailed checklist of the evidence that needs to be collected or produced to evaluate the potential usefulness of a new molecular diagnostic test. This tool is called GETT, for Genetic testing Evidence Tracking Tool. GETT allows 1) researchers to summarize the current evidence and to identify knowledge gaps for further research and; 2) stakeholders to collect data related to a given molecular test and improve their decision-making process. GETT comprises 72 clearly defined items/questions, grouped into 10 categories and 26 sub-themes, including an overview of disease epidemiology and genetics, the available diagnostic tools, and their analytical and clinical performances, availability of quality control programs, laboratory and clinical best practice guidelines, clinical utility, and impact on health care and psycho-social, ethical and legal implications. It also includes a summary of the evidence available and attempts to prioritise knowledge gaps related to the testing. We also compare GETT to other existing frameworks. This systematic evidence-based tracking tool, which is more detailed than existing frameworks and provides clear definition for each item, will help streamline collection of the available evidence to appraise the potential for clinical application of new molecular diagnostic tests and prioritize research to produce the evidence-base relative to the clinical implementation of molecular diagnostic tests.
Self-reports of levels of physical exercise, experienced bodily changes, and attitudinal and well-being variables were obtained from 407 adults, aged 26 to 95 years. The purpose was to assess the relative magnitudes of the experienced... more
Self-reports of levels of physical exercise, experienced bodily changes, and attitudinal and well-being variables were obtained from 407 adults, aged 26 to 95 years. The purpose was to assess the relative magnitudes of the experienced benefits of exercise across the exercise continuum. Cluster analyses identified three groups at each of four age levels: a) sedentary people who experienced negative bodily changes; b) modest exercisers who reported the most positive bodily changes; and c) high exercisers who reported only minimal bodily changes. Psychological barriers to exercise among sedentary people included negative exercise attitudes, attributions of negative bodily changes to aging, and low levels of exercise motivation and self-efficacy. Modest and high exercisers both scored high on attitude and well-being variables.
Activity engagement has long been linked to improved subjective well-being (SWB) in old age. However, recent studies testing Vallerand et al.'s (2003) Dualistic Model of Passion... more
Activity engagement has long been linked to improved subjective well-being (SWB) in old age. However, recent studies testing Vallerand et al.'s (2003) Dualistic Model of Passion suggest that the type of passionate activity that underlies activity engagement might influence the extent to which individuals benefit from an active lifestyle. In the present article we examined the relationship between harmonious and obsessive passionate activities and subjective well-being in older adults. Results showed that harmonious passion, through its influence on positive affect experienced during activity engagement, is associated with increases in SWB, whereas obsessive passion is associated with decreases in SWB. Engagement in passionate activities might be beneficial for older adults when a passionate activity is harmonious, but detrimental when a passionate activity is obsessive.
Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of... more
Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P…
Inherited monogenic disease has an enormous impact on the well-being of children and their families. Over half of the children living with one of these conditions are without a molecular diagnosis because of the rarity of the disease, the... more
Inherited monogenic disease has an enormous impact on the well-being of children and their families. Over half of the children living with one of these conditions are without a molecular diagnosis because of the rarity of the disease, the marked clinical heterogeneity, and the reality that there are thousands of rare diseases for which causative mutations have yet to be identified. It is in this context that in 2010 a Canadian consortium was formed to rapidly identify mutations causing a wide spectrum of pediatric-onset rare diseases by using whole-exome sequencing. The FORGE (Finding of Rare Disease Genes) Canada Consortium brought together clinicians and scientists from 21 genetics centers and three science and technology innovation centers from across Canada. From nation-wide requests for proposals, 264 disorders were selected for study from the 371 submitted; disease-causing variants (including in 67 genes not previously associated with human disease; 41 of these have been genet...
Vallerand and his colleagues (Vallerand & Blanchard, 1999; Vallerand, Blanchard, Koestner, & Gagné, 2001) have recently proposed a new concept of passion. According to these authors, passion refers to a strong inclination toward an... more
Vallerand and his colleagues (Vallerand & Blanchard, 1999; Vallerand, Blanchard, Koestner, & Gagné, 2001) have recently proposed a new concept of passion. According to these authors, passion refers to a strong inclination toward an activity that we like, find important, and in which we invest time. Vallerand et al. have identified two types of passion: obsessive and harmonious. Obsessive passion refers to an internal pressure that forces an individual to engage in the activity. Harmonious passion, on the other hand, refers to an internal force that leads an individual to choose freely to engage in an activity. While obsessive passion has been shown in some circumstances to lead to negative psychological and physical consequences, harmonious passion generally leads to positive psychological and physical consequences. The purpose of the present research was to validate a measure of passion toward gambling: the Gambling Passion Scale (GPS). The GPS consists of two subscales (obsessive ...
The fragile X mental retardation (FXMR) syndrome is one of the most frequent causes of mental retardation. Affected individuals display a wide range of additional characteristic features including behavioural and physical phenotypes, and... more
The fragile X mental retardation (FXMR) syndrome is one of the most frequent causes of mental retardation. Affected individuals display a wide range of additional characteristic features including behavioural and physical phenotypes, and the extent to which individuals are affected is highly variable. For these reasons, elucidation of the pathophysiology of this disease has been an important challenge to the scientific community. 1991 marks the year of the discovery of both the FMR1 gene mutations involved in this disease, and of their dynamic nature. Although a mouse model for the disease has been available for 16 years and extensive research has been performed on the FMR1 protein (FMRP), we still understand little about how the disease develops, and no treatment has yet been shown to be effective. In this review, we summarise current knowledge on FXMR with an emphasis on the technical challenges of molecular diagnostics, on its prevalence and dynamics among populations, and on the...
The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF ≤ 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly... more
The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF ≤ 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants, as well as rare, population-specific, coding variants. Here we identify novel non-coding genetic variants with large effects on BMD (ntotal = 53,236) and fracture (ntotal = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel loc...
Prenatal screening tests for Down syndrome (DS) are routine in many developed countries and new tests are rapidly becoming available. Decisions about prenatal screening are increasingly complex with each successive test, and pregnant... more
Prenatal screening tests for Down syndrome (DS) are routine in many developed countries and new tests are rapidly becoming available. Decisions about prenatal screening are increasingly complex with each successive test, and pregnant women need information about risks and benefits as well as clarity about their values. Decision aids (DAs) can help healthcare providers support women in this decision. Using an environmental scan, we aimed to identify publicly available DAs focusing on prenatal screening/diagnosis for Down syndrome that provide effective support for decision making. Data sources searched were the Decision Aids Library Inventory (DALI) of the Ottawa Patient Decision Aids Research Group at the Ottawa Health Research Institute; Google searches on the internet; professional organizations, academic institutions and other experts in the field; and references in existing systematic reviews on DAs. Eligible DAs targeted pregnant women, focused on prenatal screening and/or diag...
