Complex‐trait genetics has advanced dramatically through methods to estimate the heritability tagged by SNPs, both genome‐wide and in genomic regions of interest such as those defined by functional annotations. The models underlying many of these analyses are inadequate, and consequently many SNP‐heritability results published to date are inaccurate. Here, we review the modelling issues, both for analyses based on individual genotype data and association test statistics, highlighting the role of a low‐dimensional model for the heritability of each SNP. We use (...) state‐of‐art models to present updated results about how heritability is distributed with respect to functional annotations in the human genome, and how it varies with allele frequency, which can reflect purifying selection. Our results give finer detail to the picture that has emerged in recent years of complex trait heritability widely dispersed across the genome. Confounding due to population structure remains a problem that summary statistic analyses cannot reliably overcome. Also see the video abstract here: https://youtu.be/WC2u03V65MQ. (shrink)

Humans' voice offers the widest variety of motor phenomena of any human activity. However, its clinical evaluation in people with movement disorders such as Parkinson's disease lags behind current knowledge on advanced analytical automatic speech processing methodology. Here, we use deep learning-based speech processing to differentially analyze voice recordings in 14 people with PD before and after dopaminergic medication using personalized Convolutional Recurrent Neural Networks and Phone Attribute Codebooks. p-CRNN yields an accuracy of 82.35% in the binary classification of ON (...) and OFF motor states at a sensitivity/specificity of 0.86/0.78. The PAC-based approach's accuracy was slightly lower with 73.08% at a sensitivity/specificity of 0.69/0.77, but this method offers easier interpretation and understanding of the computational biomarkers. Both p-CRNN and PAC provide a differentiated view and novel insights into the distinctive components of the speech of persons with PD. Both methods detect voice qualities that are amenable to dopaminergic treatment, including active phonetic and prosodic features. Our findings may pave the way for quantitative measurements of speech in persons with PD. (shrink)