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Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement.
Methods
We conducted a genome-wide association study (GWAS) of nicotine dependence defined using the Diagnostic and Statistical Manual of Mental Disorders (DSM-NicDep) in 61,861 individuals (47,884 of European ancestry [EUR], 10,231 of African ancestry, and 3,746 of East Asian ancestry) and compared the results to other nicotine-related phenotypes.
Results
We replicated the well-known association at the CHRNA5 locus (lead single-nucleotide polymorphism [SNP]: rs147144681, p = 1.27E−11 in EUR; lead SNP = rs2036527, p = 6.49e−13 in cross-ancestry analysis). DSM-NicDep showed strong positive genetic correlations with cannabis use disorder, opioid use disorder, problematic alcohol use, lung cancer, material deprivation, and several psychiatric disorders, and negative correlations with respiratory function and educational attainment. A polygenic score of DSM-NicDep predicted DSM-5 tobacco use disorder criterion count and all 11 individual diagnostic criteria in the independent National Epidemiologic Survey on Alcohol and Related Conditions-III sample. In genomic structural equation models, DSM-NicDep loaded more strongly on a previously identified factor of general addiction liability than a “problematic tobacco use” factor (a combination of cigarettes per day and nicotine dependence defined by the Fagerström Test for Nicotine Dependence). Finally, DSM-NicDep showed a strong genetic correlation with a GWAS of tobacco use disorder as defined in electronic health records (EHRs).
Conclusions
Our results suggest that combining the wide availability of diagnostic EHR data with nuanced criterion-level analyses of DSM tobacco use disorder may produce new insights into the genetics of this disorder.
To determine the incidence of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection among healthcare personnel (HCP) and to assess occupational risks for SARS-CoV-2 infection.
Design:
Prospective cohort of healthcare personnel (HCP) followed for 6 months from May through December 2020.
Setting:
Large academic healthcare system including 4 hospitals and affiliated clinics in Atlanta, Georgia.
Participants:
HCP, including those with and without direct patient-care activities, working during the coronavirus disease 2019 (COVID-19) pandemic.
Methods:
Incident SARS-CoV-2 infections were determined through serologic testing for SARS-CoV-2 IgG at enrollment, at 3 months, and at 6 months. HCP completed monthly surveys regarding occupational activities. Multivariable logistic regression was used to identify occupational factors that increased the risk of SARS-CoV-2 infection.
Results:
Of the 304 evaluable HCP that were seronegative at enrollment, 26 (9%) seroconverted for SARS-CoV-2 IgG by 6 months. Overall, 219 participants (73%) self-identified as White race, 119 (40%) were nurses, and 121 (40%) worked on inpatient medical-surgical floors. In a multivariable analysis, HCP who identified as Black race were more likely to seroconvert than HCP who identified as White (odds ratio, 4.5; 95% confidence interval, 1.3–14.2). Increased risk for SARS-CoV-2 infection was not identified for any occupational activity, including spending >50% of a typical shift at a patient’s bedside, working in a COVID-19 unit, or performing or being present for aerosol-generating procedures (AGPs).
Conclusions:
In our study cohort of HCP working in an academic healthcare system, <10% had evidence of SARS-CoV-2 infection over 6 months. No specific occupational activities were identified as increasing risk for SARS-CoV-2 infection.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Alcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these disorders.
Methods
We used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific.
Results
We identified 55 independent genome-wide significant single nucleotide polymorphisms with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (p = 0.001).
Conclusions
Our findings provide further evidence that SCZ shares meaningful genetic overlap with AUD.
Among 353 healthcare personnel in a longitudinal cohort in 4 hospitals in Atlanta, Georgia (May–June 2020), 23 (6.5%) had severe acute respiratory coronavirus virus 2 (SARS-CoV-2) antibodies. Spending >50% of a typical shift at the bedside (OR, 3.4; 95% CI, 1.2–10.5) and black race (OR, 8.4; 95% CI, 2.7–27.4) were associated with SARS-CoV-2 seropositivity.
Understanding place-based contributors to health requires geographically and culturally diverse study populations, but sharing location data is a significant challenge to multisite studies. Here, we describe a standardized and reproducible method to perform geospatial analyses for multisite studies. Using census tract-level information, we created software for geocoding and geospatial data linkage that was distributed to a consortium of birth cohorts located throughout the USA. Individual sites performed geospatial linkages and returned tract-level information for 8810 children to a central site for analyses. Our generalizable approach demonstrates the feasibility of geospatial analyses across study sites to promote collaborative translational research.
How neighbourhood characteristics affect the physical safety of people with mental illness is unclear.
Aims
To examine neighbourhood effects on physical victimisation towards people using mental health services.
Method
We developed and evaluated a machine-learning-derived free-text-based natural language processing (NLP) algorithm to ascertain clinical text referring to physical victimisation. This was applied to records on all patients attending National Health Service mental health services in Southeast London. Sociodemographic and clinical data, and diagnostic information on use of acute hospital care (from Hospital Episode Statistics, linked to Clinical Record Interactive Search), were collected in this group, defined as ‘cases’ and concurrently sampled controls. Multilevel logistic regression models estimated associations (odds ratios, ORs) between neighbourhood-level fragmentation, crime, income deprivation, and population density and physical victimisation.
Results
Based on a human-rated gold standard, the NLP algorithm had a positive predictive value of 0.92 and sensitivity of 0.98 for (clinically recorded) physical victimisation. A 1 s.d. increase in neighbourhood crime was accompanied by a 7% increase in odds of physical victimisation in women and an 13% increase in men (adjusted OR (aOR) for women: 1.07, 95% CI 1.01–1.14, aOR for men: 1.13, 95% CI 1.06–1.21, P for gender interaction, 0.218). Although small, adjusted associations for neighbourhood fragmentation appeared greater in magnitude for women (aOR = 1.05, 95% CI 1.01–1.11) than men, where this association was not statistically significant (aOR = 1.00, 95% CI 0.95–1.04, P for gender interaction, 0.096). Neighbourhood income deprivation was associated with victimisation in men and women with similar magnitudes of association.
Conclusions
Neighbourhood factors influencing safety, as well as individual characteristics including gender, may be relevant to understanding pathways to physical victimisation towards people with mental illness.
Breakthrough Listen is a 10-yr initiative to search for signatures of technologies created by extraterrestrial civilisations at radio and optical wavelengths. Here, we detail the digital data recording system deployed for Breakthrough Listen observations at the 64-m aperture CSIRO Parkes Telescope in New South Wales, Australia. The recording system currently implements two modes: a dual-polarisation, 1.125-GHz bandwidth mode for single-beam observations, and a 26-input, 308-MHz bandwidth mode for the 21-cm multibeam receiver. The system is also designed to support a 3-GHz single-beam mode for the forthcoming Parkes ultra-wideband feed. In this paper, we present details of the system architecture, provide an overview of hardware and software, and present initial performance results.
We sought to investigate the relationship between neuroticism and depression in an elderly cohort. In this paper, we describe the methods of an National Institute of Mental Health—NIMH-supported study and present findings among the cohort enrolled to date.
Methods:
We used the NEO Personality Inventory to assess neuroticism, and we employed several cognitive neuroscience-based measures to examine emotional control.
Results:
Compared with a group of 27 non-depressed older control subjects, 33 older depressed subjects scored higher on measures of state and trait anxiety and neuroticism. On our experimental neuroscience-based measures, depressed subjects endorsed more negative words compared with controls on an emotional characterization test. In addition, we found a significant group-by-congruency effect on an emotional interference test where subjects were asked to identify the face's emotional expression while ignoring the words “fear” or “happy” labeled across the face.
Conclusion:
Thus, in this preliminary work, we found significant differences in measures of neuroticism and emotional controls among older adults with and without depression.
There is currently some debate as to whether hippocampus mediates contextual cueing. In the present study, we examined contextual cueing in patients diagnosed with mild cognitive impairment (MCI) and healthy older adults, with the main goal of investigating the role of hippocampus in this form of learning. Amnestic MCI (aMCI) patients and healthy controls completed the contextual cueing task, in which they were asked to search for a target (a horizontal T) in an array of distractors (rotated L’s). Unbeknownst to them, the spatial arrangement of elements on some displays was repeated thus making the configuration a contextual cue to the location of the target. In contrast, the configuration for novel displays was generated randomly on each trial. The difference in response times between repeated and novel configurations served as a measure of contextual learning. aMCI patients, as a group, were able to learn spatial contextual cues as well as healthy older adults. However, better learning on this task was associated with higher hippocampal volume, particularly in right hemisphere. Furthermore, contextual cueing performance was significantly associated with hippocampal volume, even after controlling for age and MCI status. These findings support the role of the hippocampus in learning of spatial contexts, and also suggest that the contextual cueing paradigm can be useful in detecting neuropathological changes associated with the hippocampus. (JINS, 2015, 21, 285–296)