We introduce two novel methods for multivariate genome-wide-association meta-analysis (GWAMA) of related traits that correct for sample overlap. A broad range of simulation scenarios supports the added value of our multivariate methods relative to univariate GWAMA. We applied the novel methods to life satisfaction, positive affect, neuroticism, and depressive symptoms, collectively referred to as the well-being spectrum (Nobs = 2,370,390), and found 304 significant independent signals. Our multivariate approaches resulted in a 26% increase in the number of independent signals relative to the four univariate GWAMAs and in an ~57% increase in the predictive power of polygenic risk scores. Supporting transcriptome- and methylome-wide analyses (TWAS and MWAS, respectively) uncovered an additional 17 and 75 independent loci, respectively. Bioinformatic analyses, based on gene expression in brain tissues and cells, showed that genes differentially expressed in the subiculum and GABAergic interneurons are enriched in their effect on the well-being spectrum.
DOCUMENT
Objective The evaluation of voice quality is a major component of voice assessment. The aim of the present study was to develop a new multivariate acoustic model for the evaluation of breathiness. Method Concatenated voice samples of continuous speech and the sustained vowel [a:] from 970 subjects with dysphonia and 88 vocally healthy subjects were perceptually judged for breathiness severity. Acoustic analyses were conducted on the same concatenated voice samples after removal of the non-voiced segments of the continuous speech sample. The development of an acoustic model for breathiness was based on stepwise multiple linear regression analysis. Concurrent validity, diagnostic accuracy, and cross validation were statistically verified on the basis of the Spearman rank-order correlation coefficient (rs), several estimates of the receiver operating characteristics plus the likelihood ratio, and iterated internal cross correlations. Results Ratings of breathiness from four experts with moderate reliability were used. Stepwise multiple regression analysis yielded a nine-variable acoustic model for the multiparametric measurement of breathiness (Acoustic Breathiness Index [ABI]). A strong correlation was found between ABI and auditory-perceptual rating (rs = 0.840, P = 0.000). The cross correlations confirmed a comparably high degree of association. Additionally, the receiver operating characteristics and likelihood ratio results showed the best diagnostic outcome at a threshold of ABI = 3.44 with a sensitivity of 82.4% and a specificity of 92.9%. Conclusions This study developed a new acoustic multivariate correlate for the evaluation of breathiness in voice. The ABI model showed valid and robust results and is therefore proposed as a new acoustic index for the evaluation of breathiness.
LINK
Objective: To predict mortality by disability in a sample of 479 Dutch community-dwelling people aged 75 years or older. Methods: A longitudinal study was carried out using a follow-up of seven years. The Groningen Activity Restriction Scale (GARS), a self-reported questionnaire with good psychometric properties, was used for data collection about total disability, disability in activities in daily living (ADL) and disability in instrumental activities in daily living (IADL). The mortality dates were provided by the municipality of Roosendaal (a city in the Netherlands). For analyses of survival, we used Kaplan–Meier analyses and Cox regression analyses to calculate hazard ratios (HR) with 95% confidence intervals (CI). Results: All three disability variables (total, ADL and IADL) predicted mortality, unadjusted and adjusted for age and gender. The unadjusted HRs for total, ADL and IADL disability were 1.054 (95%-CI: [1.039;1.069]), 1.091 (95%-CI: [1.062;1.121]) and 1.106 (95%-CI: [1.077;1.135]) with p-values <0.001, respectively. The AUCs were <0.7, ranging from 0.630 (ADL) to 0.668 (IADL). Multivariate analyses including all 18 disability items revealed that only “Do the shopping” predicted mortality. In addition, multivariate analyses focusing on 11 ADL items and 7 IADL items separately showed that only the ADL item “Get around in the house” and the IADL item “Do the shopping” significantly predicted mortality. Conclusion: Disability predicted mortality in a seven years follow-up among Dutch community-dwelling older people. It is important that healthcare professionals are aware of disability at early stages, so they can intervene swiftly, efficiently and effectively, to maintain or enhance the quality of life of older people.
MULTIFILE
