Shared genetic risk between eating disorder- and substance-use-related phenotypes:Evidence from genome-wide association studies

First published: 16 February 202

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Development of auditory function in the tammar wallaby Macropus eugenii

Auditory brainstem responses (ABRs) were evoked in developing wallabies by click and tone burst stimuli delivered by bone conduction and air conduction, at progressive stages of post-natal (pouch) life. ABRs were recorded through the onset of auditory responses (95-110 days), the opening of the external ear canal (125-130 days) and the maturation of ABR thresholds and latencies to values corresponding to those in adults (> 180 days). ABRs were evoked in response to bone-conducted clicks some days prior to the age at which an acoustically evoked response was first observed (around 95 days of pouch life). ABRs could be evoked by bone-conducted and intense air- conducted stimuli prior to opening of the ear canal. A trend of decreasing threshold and latency with age was observed for both modes of stimulation. The morphology of the ABR became more complex, according to both increased age and increased stimulus intensity. The ABR waveforms indicated relatively greater mechanosensitivity to bone-conducted stimuli than to air-conducted stimuli, prior to opening of the ear canal. Following opening of the ear canal, thresholds to air-conducted clicks and tones were substantially reduced and decreased further over the next 10-20 days, while thresholds to bone-conducted clicks continued slowly to decrease. Thresholds to tone bursts in the centre frequency range (4-12 kHz) remained less than those for low (0.5-1.5 kHz) and higher (16 kHz) frequencies. Latencies of an identified peak in ABR waveforms characteristically decreased with age (at constant stimulus intensity) and with stimulus intensity (for a given age). ABR waveforms obtained at progressive ages, but judged to be at corresponding sensation levels, underwent maturational changes, independent of conductive aspects of the wallabies' hearing, for 2-3 weeks after opening of the ear canal