Eligibility for antiamyloid treatment: preparing for disease-modifying therapies for Alzheimer's disease.

Background: Disease-modifying therapies (DMTs) for Alzheimer's disease (AD) have early evidence of efficacy. Widespread delivery of DMTs will require major service reconfiguration. Treatment pathways will need to include triaging for eligibility, regular infusions and baseline and follow-up MRI scanning.

Schizophrenia polygenic risk scores, clinical variables and genetic pathways as predictors of phenotypic traits of bipolar I disorder.

Aim: We investigated the predictive value of polygenic risk scores (PRS) derived from the schizophrenia GWAS (Trubetskoy et al., 2022) (SCZ3) for phenotypic traits of bipolar disorder type-I (BP-I) in 1878 BP-I cases and 2751 controls from Romania and UK.

Methods: We used PRSice-v2.

Predicting ADHD in alcohol dependence using polygenic risk scores for ADHD.

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with a high degree of comorbidity, including substance misuse. We aimed to assess whether ADHD polygenic risk scores (PRS) could predict ADHD diagnosis in alcohol dependence (AD). ADHD PRS were generated for 1223 AD subjects with ADHD diagnosis information and 1818 healthy controls.

Genome-wide association study of antisocial personality disorder diagnostic criteria provides evidence for shared risk factors across disorders.

Introduction: While progress has been made in determining the genetic basis of antisocial behaviour, little progress has been made for antisocial personality disorder (ASPD), a condition that often co-occurs with other psychiatric conditions including substance use disorders, attention deficit hyperactivity disorder (ADHD), and anxiety disorders. This study aims to improve the understanding of the genetic risk for ASPD and its relationship with other disorders and traits.

Methods: We conducted a genome-wide association study (GWAS) of the number of ASPD diagnostic criteria data from 3217 alcohol-dependent participants recruited in the UK (UCL, N = 644) and the USA (Yale-Penn, N = 2573).

Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders.

Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk.

Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH.

The influence of regression models on genome-wide association studies of alcohol dependence: a comparison of binary and quantitative analyses.

Introduction: Genome-wide association studies (GWAS) of alcohol dependence syndrome (ADS) offer a platform to detect genetic risk loci. However, the majority of the ADS GWAS undertaken, to date, have utilized a case-control design and have failed to identify consistently replicable loci with the exception of protective variants within the alcohol metabolizing genes, notably ADH1B. The ADS phenotype shows considerable variability which means that the use of quantitative variables as a proxy for the severity of ADS has the potential to facilitate identification of risk loci by increasing statistical power.

"Falling through the cracks"; Stakeholders' views around the concept and diagnosis of mild cognitive impairment and their understanding of dementia prevention.

Objectives: Many people live with an awareness of mild cognitive changes that increase their dementia risk. Previous authors describe the uncertainties of this liminal state, between cognitive health and dementia, where being "at risk" can itself be an illness. We ask how services respond to people with memory concerns currently, and how a future, effective and inclusive dementia prevention intervention might be structured for people with memory concerns.

Predictive power of the ADHD GWAS 2019 polygenic risk scores in independent samples of bipolar patients with childhood ADHD.

Background: Although there is evidence of genetic correlation between bipolar disorder (BP) and ADHD, the extent of the shared genetic risk and whether childhood ADHD (cADHD) influences the characteristics of the adult BP remain unclear. Our objectives were: (i) to test the ability of polygenic risk scores (PRS) derived from the latest PGC ADHD-GWAS (Demontis et al., 2019) to predict the presence of cADHD in BP patients; (ii) to examine the hypothesis that BP preceded by cADHD is a BP subtype with particular clinical traits and (iii) partially shares its molecular basis with ADHD.

Genetic association and functional characterization of MCPH1 gene variation in bipolar disorder and schizophrenia.

A rare microcephalin 1 gene (MCPH1) variant rs61749465A>G (p.Asp61Gly) with prior evidence for association with schizophrenia (p = 3.78 × 10 ) was tested for association in 2,300 bipolar disorder (BPD) participants, 1,930 SCZ participants and 1,820 normal comparison subjects.

Genome-wide association study identifies glutamate ionotropic receptor GRIA4 as a risk gene for comorbid nicotine dependence and major depression.

Smoking and major depression frequently co-occur, at least in part due to shared genetic risk. However, the nature of the shared genetic basis is poorly understood. To detect genetic risk variants for comorbid nicotine dependence (ND) and major depression (MD), we conducted genome-wide association study (GWAS) in two samples of African-American participants (Yale-Penn 1 and 2) using linear mixed model, followed by meta-analysis.

Mutation intolerant genes and targets of FMRP are enriched for nonsynonymous alleles in schizophrenia.

Risk of schizophrenia is conferred by alleles occurring across the full spectrum of frequencies from common SNPs of weak effect through to ultra rare alleles, some of which may be moderately to highly penetrant. Previous studies have suggested that some of the risk of schizophrenia is attributable to uncommon alleles represented on Illumina exome arrays. Here, we present the largest study of exomic variation in schizophrenia to date, using samples from the United Kingdom and Sweden (10,011 schizophrenia cases and 13,791 controls).

Identification of rare nonsynonymous variants in SYNE1/CPG2 in bipolar affective disorder.

Background: Bipolar affective disorder (BPD) is a severe mood disorder with a prevalence of ∼1.5% in the population. The pathogenesis of BPD is poorly understood; however, a strong heritable component has been identified.