Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

VLF measurements and modeling of the D-region response to the 2017 total solar eclipse

Abstract In this paper, we report measurements in Colorado and Utah of the disturbed very-low-frequency (VLF) signals from the NML Navy transmitter in North Dakota during the 2017 solar eclipse. Using an occultation mask of solar fluxes together with detailed chemistry and VLF propagation simulations, we quantify the D-region response to the eclipse, in terms of electron density variation, as well as the expected signatures of VLF transmitter signals. The VLF measurements, including an anomalous amplitude enhancement recorded in UT, can be quantitatively explained using the Wait and Spies ionospheric profile with a sharpness parameter of β = 0.3 km⁻¹ above ~55 km and an increase in the D-region ionosphere height of Δh′ ≃ 8 km. This sharpness parameter is consistent with previously reported rocket measurements and first-principles calculations. The best-fit results suggest a reduction of D-region electron density by ~90% during the eclipse in the D-region, implying an occultation of Lyman-α by nearly 99%. This finding agrees with detailed calculations of time-dependent obscuration factors utilizing the He 30.4-nm images from Solar Dynamics Observatory as a proxy for the distribution of Lyman-α across the solar disk and limb. Moreover, the present results show that subionospheric VLF propagation is sensitive to the sharpness parameter of the electron density profile in the D-region. Previously reported first-principles simulations have shown that the sharpness parameter is mostly controlled by the background concentration of minor neutral species. Thus, the VLF technique can be likely used to remotely sense these neutral species at and below the effective reflection altitudes of VLF waves

Mid-Latitude Temperatures at 87 km: Results From Multi-Instrument Fourier Analysis

Using a novel Fourier fitting method we combine two years of mid-latitude temperature measurements at 87 km from the High Resolution Doppler Imager, the Colorado State University lidar, and the Peach Mountain Interferometer. After accounting for calibration bias, significant local-time variations on the order of 10 K were observed. Stationary planetary waves with amplitudes up to 10 K were observed during winter, with weaker wave amplitudes occurring during other seasons. Because of calibration biases among these instruments, we could estimate the annual mean temperature to no better than 193.5 plus or minus 8.5 K

Middle Atmosphere Variability and Model Uncertainties as Investigated in the Framework of the ARISE Project

International audienc

New insights into the genetic etiology of Alzheimer’s disease and related dementias

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

New insights into the genetic etiology of Alzheimer’s disease and related dementias

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele