Genome-wide association studies have shown unequivocally that common complex disorders have a polygenic genetic architecture and have enabled researchers to identify genetic variants associated with ...diseases. These variants can be combined into a polygenic risk score that captures part of an individual's susceptibility to diseases. Polygenic risk scores have been widely applied in research studies, confirming the association between the scores and disease status, but their clinical utility has yet to be established. Polygenic risk scores may be used to estimate an individual's lifetime genetic risk of disease, but the current discriminative ability is low in the general population. Clinical implementation of polygenic risk score (PRS) may be useful in cohorts where there is a higher prior probability of disease, for example, in early stages of diseases to assist in diagnosis or to inform treatment choices. Important considerations are the weaker evidence base in application to non-European ancestry and the challenges in translating an individual's PRS from a percentile of a normal distribution to a lifetime disease risk. In this review, we consider how PRS may be informative at different points in the disease trajectory giving examples of progress in the field and discussing obstacles that need to be addressed before clinical implementation.
Genome-wide association studies have made strides in identifying common variation associated with disease. The modest effect sizes preclude risk prediction based on single genetic variants, but ...polygenic risk scores that combine thousands of variants show some predictive ability across a range of complex traits and diseases, including neuropsychiatric disorders. Here, we consider the potential for translation to clinical use.
A low loss metamaterial unit cell is presented with an integrated GaAs air-bridged Schottky diode to produce a dynamically tunable reflective phase shifter that is capable of up to 250° phase shift ...with an experimentally measured average loss of 6.2 dB at V-band. The air-bridged Schottky diode provides a tuneable capacitance in the range between 30 and 50 fF under an applied reverse voltage bias. This can be used to alter the resonant frequency and phase response of a split patch unit cell of a periodic metasurface. The air-bridged diode die, which is flip-chip soldered to the patch, has ultra-low parasitic capacitance and resistance. Simulated and measured results are presented which verify the potential for the attainment of diode switching speeds with acceptable losses at mmWave frequencies. Furthermore the study shows that this diode-based unit cell can be integrated into metamaterial components, which have potential applications in future mmWave antenna beam-steering, intelligent reflecting surfaces for 6G communications, reflect-arrays, transmit-arrays or holographic antennas.
Genome-wide association studies (GWASs) have focused primarily on populations of European descent, but it is essential that diverse populations become better represented. Increasing diversity among ...study participants will advance our understanding of genetic architecture in all populations and ensure that genetic research is broadly applicable. To facilitate and promote research in multi-ancestry and admixed cohorts, we outline key methodological considerations and highlight opportunities, challenges, solutions, and areas in need of development. Despite the perception that analyzing genetic data from diverse populations is difficult, it is scientifically and ethically imperative, and there is an expanding analytical toolbox to do it well.
With increasing representation of global populations in genetic studies, there is an opportunity for advanced methods development and a need for consensus “best practices” for analyzing datasets. We provide background on the scientific and ethical importance of including underrepresented groups in genetics research and offer guidance for genome-wide analysis of ancestrally diverse study cohorts.
Free space (also termed quasi‐optical) metasurfaces have recently been designed and proposed as new types of polarizers that allow polarization control of an impinging wave in ways that are not ...possible with conventional designs. However, existing methods for tunable metasurface polarizers are not able to fully control the polarization dynamically; additionally, at mm‐wave and submillimeter bands, they typically suffer from high losses, which are predominantly produced by the inherent limitations of the tuning elements or materials. An electromechanically tunable reflection polariser that has the ability to fully control the polarization of an impinging wave has been designed, fabricated, and experimentally tested in a frequency band centered at 57 GHz. The proposed technique utilizes a variable air cavity between a periodic metasurface array and a ground plane, controlled by a piezoelectric actuator. The periodic metasurface element consists of two slightly different cross‐shaped metallic elements arranged in a periodic triangular lattice. Full‐wave simulations are presented and experimentally validated with measurements. The proposed approach is scalable from microwave up to THz frequencies with low‐loss performance due to the nature of the tuning technology whereby the tuning element is not interfering with the electromagnetic waves in the structure.
A novel electromechanical quasi‐optical metasurface provides full control over the polarization of impinging waves, as tested at 57 GHz. The tunable metasurface utilizes a piezoelectric actuator‐controlled variable air cavity and distinctive cross‐shaped metallic elements. Its scalable, low‐loss design operates efficiently across microwave to THz frequencies due to the nature of the tuning technology.
Vassos discusses the study by Rognli et al. on a Norwegian Patient Registry study in which they identified all the inpatients and outpatients diagnosed with substance-induced psychotic disorder ...between 2010 and 2015 and used longitudinal data to establish subsequent diagnoses of chronic psychotic disorders. The authors investigated transitions to schizophrenia spectrum disorder as well as transitions to bipolar disorder, the latter of which, despite compelling evidence of an association with substance misuse, has received little attention in previous studies. They estimated 6-year cumulative rates of 27.6% for transition to schizophrenia spectrum disorder (the rate dropped to 18.8% in a sensitivity analysis that restricted the outcome to schizophrenia) and 4.5% for transition to bipolar disorder.
Abstract
Objective
The aim of this systematic review and meta-analysis was to study the association between specific environmental risk factors (ERF) and later development of Bipolar disorder and ...Psychotic depression.
Methods
A systematic search of prospective studies was conducted in MEDLINE, EMBASE and PsycINFO databases, and supplemented by hand searching, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (registration number: CRD42018092253). Selected ERF included: pre-/peri-natal factors—paternal age at birth, maternal infection, obstetric complications, perinatal stress; early childhood factors—urbanicity at birth, childhood infection, childhood adversity; later life factors—substance misuse, ethnic minority and migration, urbanicity later in life, stressful life events, and traumatic head injury. Pooled effect sizes of the association between these ERF and affective psychoses were calculated from systematically selected studies. When studies examining each ERF were insufficient for meta-analysis, results were presented narratively.
Results
Forty-six studies were included for quantitative analyses among selected ERF for affective psychosis, with significant association found for paternal age >40 years (OR 1.17, 95%CI 1.12–1.23), early (OR 1.52, 95%CI 1.07–2.17) and late (OR 1.32, 95%CI 1.05–1.67) gestational age, childhood adversity (OR 1.33, 95%CI 1.18–1.50), substance misuse (OR 2.87, 95%CI 1.63–5.50), and being from an ethnic minority (OR 1.99, 95%CI 1.39–2.84).
Conclusions
These results suggest some shared environmental load between non-affective and affective psychosis, implying generalized risks for psychosis rather than for specific diagnostic categories. Nonetheless, published studies for some ERF in the affective psychoses are scarce, and further longitudinal studies are needed.
Major depressive disorder (MDD) is defined differently across genetic research studies and this may be a key source of heterogeneity. While previous literature highlights differences between minimal ...and strict phenotypes, the components contributing to this heterogeneity have not been identified. Using the cardinal symptoms (depressed mood/anhedonia) as a baseline, we build MDD phenotypes using five components-(1) five or more symptoms, (2) episode duration, (3) functional impairment, (4) episode persistence, and (5) episode recurrence-to determine the contributors to such heterogeneity. Thirty-two depression phenotypes which systematically incorporate different combinations of MDD components were created using the mental health questionnaire data within the UK Biobank. SNP-based heritabilities and genetic correlations with three previously defined major depression phenotypes were calculated (Psychiatric Genomics Consortium (PGC) defined depression, 23andMe self-reported depression and broad depression) and differences between estimates analysed. All phenotypes were heritable (h
range: 0.102-0.162) and showed substantial genetic correlations with other major depression phenotypes (Rg range: 0.651-0.895 (PGC); 0.652-0.837 (23andMe); 0.699-0.900 (broad depression)). The strongest effect on SNP-based heritability was from the requirement for five or more symptoms (1.4% average increase) and for a long episode duration (2.7% average decrease). No significant differences were noted between genetic correlations. While there is some variation, the two cardinal symptoms largely reflect the genetic aetiology of phenotypes incorporating more MDD components. These components may index severity, however, their impact on heterogeneity in genetic results is likely to be limited.
Copy number variants (CNVs) at chromosome 16p13.11 have been associated with a range of neurodevelopmental disorders including autism, ADHD, intellectual disability and schizophrenia. Significant sex ...differences in prevalence, course and severity have been described for a number of these conditions but the biological and environmental factors underlying such sex-specific features remain unclear. We tested the burden and the possible sex-biased effect of CNVs at 16p13.11 in a sample of 10,397 individuals with a range of neurodevelopmental conditions, clinically referred for array comparative genomic hybridisation (aCGH); cases were compared with 11,277 controls. In order to identify candidate phenotype-associated genes, we performed an interval-based analysis and investigated the presence of ohnologs at 16p13.11; finally, we searched the DECIPHER database for previously identified 16p13.11 copy number variants. In the clinical referral series, we identified 46 cases with CNVs of variable size at 16p13.11, including 28 duplications and 18 deletions. Patients were referred for various phenotypes, including developmental delay, autism, speech delay, learning difficulties, behavioural problems, epilepsy, microcephaly and physical dysmorphisms. CNVs at 16p13.11 were also present in 17 controls. Association analysis revealed an excess of CNVs in cases compared with controls (OR = 2.59; p = 0.0005), and a sex-biased effect, with a significant enrichment of CNVs only in the male subgroup of cases (OR = 5.62; p = 0.0002), but not in females (OR = 1.19, p = 0.673). The same pattern of results was also observed in the DECIPHER sample. Interval-based analysis showed a significant enrichment of case CNVs containing interval II (OR = 2.59; p = 0.0005), located in the 0.83 Mb genomic region between 15.49-16.32 Mb, and encompassing the four ohnologs NDE1, MYH11, ABCC1 and ABCC6. Our data confirm that duplications and deletions at 16p13.11 represent incompletely penetrant pathogenic mutations that predispose to a range of neurodevelopmental disorders, and suggest a sex-limited effect on the penetrance of the pathological phenotypes at the 16p13.11 locus.
There is increasing evidence for shared genetic susceptibility between schizophrenia and bipolar disorder. Although genetic variants only convey subtle increases in risk individually, their ...combination into a polygenic risk score constitutes a strong disease predictor.AimsTo investigate whether schizophrenia and bipolar disorder polygenic risk scores can distinguish people with broadly defined psychosis and their unaffected relatives from controls.
Using the latest Psychiatric Genomics Consortium data, we calculated schizophrenia and bipolar disorder polygenic risk scores for 1168 people with psychosis, 552 unaffected relatives and 1472 controls.
Patients with broadly defined psychosis had dramatic increases in schizophrenia and bipolar polygenic risk scores, as did their relatives, albeit to a lesser degree. However, the accuracy of predictive models was modest.
Although polygenic risk scores are not ready for clinical use, it is hoped that as they are refined they could help towards risk reduction advice and early interventions for psychosis.Declaration of interestR.M.M. has received honoraria for lectures from Janssen, Lundbeck, Lilly, Otsuka and Sunovian.
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