49 research outputs found
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Psychometric Analysis of the Adult Sickle Cell Quality of Life Measurement Information System (ACSQ-Me) in a UK Population
Background: The Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) has been shown to be a reliable and valid questionnaire measuring health-related quality of life (HRQoL) in the US sickle cell disease (SCD) population. The study objective was to test the validity and reliability of the ASCQ-Me for use in the UK.
Methods: The US ASCQ-Me, Hospital Anxiety and Depression Scale (HADS), self-reported symptoms, and Medical Outcome Survey Short Form 36 (SF-36) were administered to 173 patients with SCD. Clinical severity was assessed by the number of painful episodes indicated by hospital admissions.
Results: The results showed that the item banks of the UK ASCQ-Me had good internal consistency. Anxiety and depression were strongly correlated with the emotional, and social item banks of the UK ASCQ-Me, with moderate correlations between the UK ASCQ-Me item banks and SF-36 components suggesting convergent validity. A confirmatory factor analysis confirmed the conceptual framework of the scale as being the same as the US ASCQ-Me, indicating construct validity. Known groups validity was found, with the ASCQ-Me being able to differentiate by SCD severity groups.
Conclusion: The analysis of the sample shows evidence of both validity and reliability of the ACCQ-Me for use in the UK SCD population
Reconstructing Druze population history
The Druze are an aggregate of communities in the Levant and Near East living almost exclusively in the mountains of Syria, Lebanon and Israel whose ~1000 year old religion formally opposes mixed marriages and conversions. Despite increasing interest in genetics of the population structure of the Druze, their population history remains unknown. We investigated the genetic relationships between Israeli Druze and both modern and ancient populations. We evaluated our findings in light of three hypotheses purporting to explain Druze history that posit Arabian, Persian or mixed Near Eastern-Levantine roots. The biogeographical analysis localised proto-Druze to the mountainous regions of southeastern Turkey, northern Iraq and southeast Syria and their descendants clustered along a trajectory between these two regions. The mixed Near Eastern-Middle Eastern localisation of the Druze, shown using both modern and ancient DNA data, is distinct from that of neighbouring Syrians, Palestinians and most of the Lebanese, who exhibit a high affinity to the Levant. Druze biogeographic affinity, migration patterns, time of emergence and genetic similarity to Near Eastern populations are highly suggestive of Armenian-Turkish ancestries for the proto-Druze
Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study
Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation
Psychiatric disorders in preclinical Huntington's disease
BACKGROUND: Psychiatric symptoms are a common feature of Huntington's disease (HD) and often precede the onset of motor and cognitive impairments. However, it remains unclear whether psychiatric changes in the preclinical period result from structural change, are a reaction to being at risk or simply a coincidental occurrence. Few studies have investigated the temporal course of psychiatric disorder across the preclinical period. OBJECTIVES: To compare lifetime and current prevalence of psychiatric disorder in presymptomatic gene carriers and non‐carriers and to examine the relationship of psychiatric prevalence in gene carriers to temporal proximity of clinical onset. METHODS: Lifetime and current psychiatric histories of 204 at risk individuals (89 gene carriers and 115 non‐carriers) were obtained using a structured clinical interview, the Composite International Diagnostic Interview. Psychiatric disorders were classified using both standardised diagnostic criteria and a more subtle symptom based approach. Follow‐up of gene carriers (n = 51) enabled analysis of the role of temporal proximity to clinical onset. RESULTS: Gene carriers and non‐carriers did not differ in terms of the lifetime frequency of clinical psychiatric disorders or subclinical symptoms. However, gene carriers reported a significantly higher rate of current depressive symptoms. Moreover, the rate of depression increased as a function of proximity to clinical onset. CONCLUSIONS: Affective disorder is an important feature of the prodromal stages of HD. The findings indicate that depression cannot be accounted for by natural concerns of being at risk. There is evidence of a window of several years in which preclinical symptoms are apparent