Safe Linkage of Cohort and Population-Based Register Data in a Genomewide Association Study on Health Care Expenditure.

There are research questions whose answers require record linkage of multiple databases that may be characterized by limited options for full data sharing. For this purpose, the Open Data Infrastructure for Social Science and Economic Innovations (ODISSEI) consortium has supported the development of the ODISSEI Secure Supercomputer (OSSC) platform that allows researchers to link cohort data to data from Statistics Netherlands and run large-scale analyses in a high-performance computing (HPC) environment. Here, we report a successful record linkage genomewide association (GWA) study on expenditure for total health, mental health, primary and hospital care, and medication. Record linkage for genotype data from 16,726 participants from the Netherlands Twin Register (NTR) with data from Statistics Netherlands was accomplished in the secure OSSC platform, followed by gene-based tests and estimation of total and single nucleotide polymorphism (SNP)-based heritability. The total heritability of expenditure ranged between 29.4% (SE 0.8) and 37.5% (SE 0.8), but GWA analyses did not identify SNPs or genes that were genomewide significantly associated with health care expenditure. SNP-based heritability was between 0.0% (SE 3.5) and 5.4% (SE 4.0) and was different from zero for mental health care and primary care expenditure. We conclude that successfully linking genotype data to administrative health care expenditure data from Statistics Netherlands is feasible and demonstrates a series of analyses on health care expenditure. The OSSC platform offers secure possibilities for analyzing linked data in large scale and realizing sample sizes required for GWA studies, providing invaluable opportunities to answer many new research questions.

Top-down and bottom-up processes in speech comprehension.

Speech comprehension includes both bottom-up and top-down processes, and imaging studies have isolated a frontal-temporal network of brain areas active during speech perception. However, the precise role of the various areas in this network during normal speech comprehension is not yet fully understood. In the present fMRI study, the signal-to-noise ratio (SNR) of spoken sentences was varied in 144 steps, and speech intelligibility was measured independently in order to study in detail its effect on the activation of brain areas involved in speech perception. Relative to noise alone, intelligible speech in noise evoked spatially extended activation in left frontal, bilateral temporal, and medial occipital brain regions. Increasing SNR led to a sigmoid-shaped increase of activation in all areas of the frontal-temporal network. The onset of the activation with respect to SNR was similar in temporal and frontal regions, but frontal activation was found to be smaller than temporal activation at the highest SNRs. Finally, only Broca's area (BA44) showed activation to unintelligible speech presented at low SNRs. These findings demonstrate distinct roles of frontal and temporal areas in speech comprehension in that temporal regions subserve bottom-up processing of speech, whereas frontal areas are more involved in top-down supplementary mechanisms.

Amplitude and phase of distortion product otoacoustic emissions in the guinea pig in an (f1 ,f2) area study.

Lower sideband distortion product otoacoustic emissions (DPOAEs), measured in the ear canal upon stimulation with two continuous pure tones, are the result of interfering contributions from two different mechanisms, the nonlinear distortion component and the linear reflection component. The two contributors have been shown to have a different amplitude and, in particular, a different phase behavior as a function of the stimulus frequencies. The dominance of either component was investigated in an extensive (f1 ,f2) area study of DPOAE amplitude and phase in the guinea pig, which allows for both qualitative and quantitative analysis of isophase contours. Making a minimum of additional assumptions, simple relations between the direction of constant phase in the (f ,f2) plane and the group delays in f1-sweep, f2-sweep, and fixed f2/f1 paradigms can be derived, both for distortion (wave-fixed) and reflection (place-fixed) components. The experimental data indicate the presence of both components in the lower sideband DPOAEs, with the reflection component as the dominant contributor for low f2/f1 ratios and the distortion component for intermediate ratios. At high ratios the behavior cannot be explained by dominance of either component.