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Childhood self-control has been linked with better health, criminal justice, and economic outcomes in adulthood in predominately white cohorts outside of the United States. We investigated whether self-control in first grade predicted success in the transition to adulthood in a longitudinal cohort of first graders who participated in a universal intervention trial to prevent poor achievement and reduce aggression in Baltimore schools. We also explored whether the intervention moderated the relationship between self-control and young adult outcomes. Teachers rated self-control using the Teacher Observation of Classroom Adaptation-Revised. Study outcomes were on-time high school graduation, college participation, teen pregnancy, substance use disorder, criminal justice system involvement, and incarceration (ages 19–26). Latent profile analysis was used to identify classes of childhood self-control. A high self-control class (n = 279, 48.1%), inattentive class (n = 201, 35.3%), and inattentive/hyperactive class (n = 90, 16.6%) were identified. Children with better self-control were more likely to graduate on time and attend college; no significant class differences were found for teen pregnancy, substance use disorder, criminal justice system involvement, or incarceration. A classroom-based intervention reduced criminal justice system involvement and substance use disorder among children with high self-control. Early interventions to promote child self-control may have long-term individual and social benefits.
Cesario claims that all bias research tells us is that people “end up using the information they have come to learn as being probabilistically accurate in their daily lives” (sect. 5, para. 4). We expose Cesario's flawed assumptions about the relationship between accuracy and bias. Through statistical simulations and empirical work, we show that even probabilistically accurate responses are regularly accompanied by bias.
Background: Phase 3 COMET trial (NCT02782741) compares avalglucosidase alfa (n=51) with alglucosidase alfa (n=49) in treatment-naïve LOPD. Methods: Primary objective: determine avalglucosidase alfa effect on respiratory muscle function. Secondary/other objectives include: avalglucosidase alfa effect on functional endurance, inspiratory/expiratory muscle strength, lower/upper extremity muscle strength, motor function, health-related quality of life, safety. Results: At Week 49, change (LSmean±SE) from baseline in upright forced vital capacity %predicted was greater with avalglucosidase alfa (2.89%±0.88%) versus alglucosidase alfa (0.46%±0.93%)(absolute difference+2.43%). The primary objective, achieving statistical non-inferiority (p=0.0074), was met. Superiority testing was borderline significant (p=0.0626). Week 49 change from baseline in 6-minute walk test was 30.01-meters greater for avalglucosidase alfa (32.21±9.93m) versus alglucosidase alfa (2.19±10.40m). Positive results for avalglucosidase alfa were seen for all secondary/other efficacy endpoints. Treatment-emergent adverse events (AEs) occurred in 86.3% of avalglucosidase alfa-treated and 91.8% of alglucosidase alfa-treated participants. Five participants withdrew, 4 for AEs, all on alglucosidase alfa. Serious AEs occurred in 8 avalglucosidase alfa-treated and 12 alglucosidase alfa-treated participants. IgG antidrug antibody responses were similar in both. High titers and neutralizing antibodies were more common for alglucosidase alfa. Conclusions: Results demonstrate improvements in clinically meaningful outcome measures and a more favorable safety profile with avalglucosidase alfa versus alglucosidase alfa. Funding: Sanofi Genzyme
The North Carolina Legislature appropriated funds in 2016–2019 for the Healthy Food Small Retailer Program (HFSRP), providing small retailers located in food deserts with equipment to stock nutrient-dense foods and beverages. The study aimed to: (1) examine factors facilitating and constraining implementation of, and participation in, the HFSRP from the perspective of storeowners and (2) measure and evaluate the impact and effectiveness of investment in the HFSRP.
The current analysis uses both qualitative and quantitative assessments of storeowner perceptions and store outcomes, as well as two innovative measures of policy investment effectiveness. Qualitative semi-structured interviews and descriptive quantitative approaches, including monthly financial reports and activity forms, and end-of-programme evaluations were collected from participating HFSRP storeowners.
Eight corner stores in North Carolina that participated in the two cohorts (2016–2018; 2017–2019) of the HFSRP.
Owners of corner stores participating in the HFSRP.
All storeowners reported that the HFSRP benefitted their stores. In addition, the HFSRP had a positive impact on sales across each category of healthy food products. Storeowners reported that benefits would be enhanced with adjustments to programme administration and support. Specific suggestions included additional information regarding which healthy foods and beverages to stock; inventory management; handling of perishable produce; product display; modified reporting requirements and a more efficient process of delivering and maintaining equipment.
All storeowners reported several benefits of the HFSRP and would recommend that other storeowners participate. The barriers and challenges they reported inform potential approaches to ensuring success and sustainability of the HFSRP and similar initiatives underway in other jurisdictions.
A chloroacetamide herbicide by application timing factorial experiment was conducted in 2017 and 2018 in Mississippi to investigate chloroacetamide use in a dicamba-based Palmer amaranth management program in cotton production. Herbicides used were S-metolachlor or acetochlor, and application timings were preemergence, preemergence followed by (fb) early postemergence, preemergence fb late postemergence, early postemergence alone, late postemergence alone, and early postemergence fb late postemergence. Dicamba was included in all preemergence applications, and dicamba plus glyphosate was included with all postemergence applications. Differences in cotton and weed response due to chloroacetamide type were minimal, and cotton injury at 14 d after late postemergence application was less than 10% for all application timings. Late-season weed control was reduced up to 30% and 53% if chloroacetamide application occurred preemergence or late postemergence only, respectively. Late-season weed densities were minimized if multiple applications were used instead of a single application. Cotton height was reduced by up to 23% if a single application was made late postemergence relative to other application timings. Chloroacetamide application at any timing except preemergence alone minimized late-season weed biomass. Yield was maximized by any treatment involving multiple applications or early postemergence alone, whereas applications preemergence or late postemergence alone resulted in up to 56% and 27% yield losses, respectively. While no yield loss was reported by delaying the first of sequential applications until early postemergence, forgoing a preemergence application is not advisable given the multiple factors that may delay timely postemergence applications such as inclement weather.
Pompe disease results from lysosomal acid α-glucosidase deficiency, which leads to cardiomyopathy in all infantile-onset and occasional late-onset patients. Cardiac assessment is important for its diagnosis and management. This article presents unpublished cardiac findings, concomitant medications, and cardiac efficacy and safety outcomes from the ADVANCE study; trajectories of patients with abnormal left ventricular mass z score at enrolment; and post hoc analyses of on-treatment left ventricular mass and systolic blood pressure z scores by disease phenotype, GAA genotype, and “fraction of life” (defined as the fraction of life on pre-study 160 L production-scale alglucosidase alfa). ADVANCE evaluated 52 weeks’ treatment with 4000 L production-scale alglucosidase alfa in ≥1-year-old United States of America patients with Pompe disease previously receiving 160 L production-scale alglucosidase alfa. M-mode echocardiography and 12-lead electrocardiography were performed at enrolment and Week 52. Sixty-seven patients had complete left ventricular mass z scores, decreasing at Week 52 (infantile-onset patients, change −0.8 ± 1.83; 95% confidence interval −1.3 to −0.2; all patients, change −0.5 ± 1.71; 95% confidence interval −1.0 to −0.1). Patients with “fraction of life” <0.79 had left ventricular mass z score decreasing (enrolment: +0.1 ± 3.0; Week 52: −1.1 ± 2.0); those with “fraction of life” ≥0.79 remained stable (enrolment: −0.9 ± 1.5; Week 52: −0.9 ± 1.4). Systolic blood pressure z scores were stable from enrolment to Week 52, and no cohort developed systemic hypertension. Eight patients had Wolff–Parkinson–White syndrome. Cardiac hypertrophy and dysrhythmia in ADVANCE patients at or before enrolment were typical of Pompe disease. Four-thousand L alglucosidase alfa therapy maintained fractional shortening, left ventricular posterior and septal end-diastolic thicknesses, and improved left ventricular mass z score.
Social Media Statement: Post hoc analyses of the ADVANCE study cohort of 113 children support ongoing cardiac monitoring and concomitant management of children with Pompe disease on long-term alglucosidase alfa to functionally improve cardiomyopathy and/or dysrhythmia.
In the UK, acute mental healthcare is provided by in-patient wards and crisis resolution teams. Readmission to acute care following discharge is common. Acute day units (ADUs) are also provided in some areas.
To assess predictors of readmission to acute mental healthcare following discharge in England, including availability of ADUs.
We enrolled a national cohort of adults discharged from acute mental healthcare in the English National Health Service (NHS) between 2013 and 2015, determined the risk of readmission to either in-patient or crisis teams, and used multivariable, multilevel logistic models to evaluate predictors of readmission.
Of a total of 231 998 eligible individuals discharged from acute mental healthcare, 49 547 (21.4%) were readmitted within 6 months, with a median time to readmission of 34 days (interquartile range 10–88 days). Most variation in readmission (98%) was attributable to individual patient-level rather than provider (trust)-level effects (2.0%). Risk of readmission was not associated with local availability of ADUs (adjusted odds ratio 0.96, 95% CI 0.80–1.15). Statistically significant elevated risks were identified for participants who were female, older, single, from Black or mixed ethnic groups, or from more deprived areas. Clinical predictors included shorter index admission, psychosis and being an in-patient at baseline.
Relapse and readmission to acute mental healthcare are common following discharge and occur early. Readmission was not influenced significantly by trust-level variables including availability of ADUs. More support for relapse prevention and symptom management may be required following discharge from acute mental healthcare.
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.
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.
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).
Our findings provide further evidence that SCZ shares meaningful genetic overlap with AUD.
This study compared the level of education and tests from multiple cognitive domains as proxies for cognitive reserve.
The participants were educationally, ethnically, and cognitively diverse older adults enrolled in a longitudinal aging study. We examined independent and interactive effects of education, baseline cognitive scores, and MRI measures of cortical gray matter change on longitudinal cognitive change.
Baseline episodic memory was related to cognitive decline independent of brain and demographic variables and moderated (weakened) the impact of gray matter change. Education moderated (strengthened) the gray matter change effect. Non-memory cognitive measures did not incrementally explain cognitive decline or moderate gray matter change effects.
Episodic memory showed strong construct validity as a measure of cognitive reserve. Education effects on cognitive decline were dependent upon the rate of atrophy, indicating education effectively measures cognitive reserve only when atrophy rate is low. Results indicate that episodic memory has clinical utility as a predictor of future cognitive decline and better represents the neural basis of cognitive reserve than other cognitive abilities or static proxies like education.
Optimal management of schizophrenia in adolescents is limited by the lack of available therapies. The efficacy and tolerability of aripiprazole was investigated in this patient population.
This 6-week, randomized, double-blind, placebo controlled trial was conducted at 101 international centers, with a safety monitoring board. 13-17 year-olds with a DSM-IV diagnosis of schizophrenia were randomized to placebo, or a fixed dose of aripiprazole 10 mg or 30 mg reached after a 5 or 11 day titration, respectively. The primary endpoint was mean change from baseline on the PANSS Total score at week 6. Secondary endpoints included the PANSS Positive and Negative subscales, and CGI Improvement score. Tolerabilility assessements included frequency and severity of adverse events, as well as blood chemistries, metabolic parameters and weight gain.
Over 85% of 302 patients completed this study. Both 10 mg and 30 mg doses were superior to placebo on the primary endpoint (PANSS total), with significant differences observed as early as Week 1 (30mg). Both doses showed significant improvement on the PANSS Positive and CGI-I scales; and the 10 mg dose group was superior on PANSS Negative score. Approximately 5% of aripiprazole patients discontinued due to AEs. Weight gain and changes in prolactin were minimal.
10mg and 30mg doses of aripiprazole were superior to placebo in the treatment of adolescents with schizophrenia. Aripiprazole was well tolerated, in general, with few discontinuations due to AEs. EPS was the most common AE. Change in body weight was similar to placebo.
To advance the quality of mental healthcare in Europe by developing guidance on implementing quality assurance.
We performed a systematic literature search on quality assurance in mental healthcare and the 522 retrieved documents were evaluated by two independent reviewers (B.J. and J.Z.). Based on these evaluations, evidence tables were generated. As it was found that these did not cover all areas of mental healthcare, supplementary hand searches were performed for selected additional areas. Based on these findings, fifteen graded recommendations were developed and consented by the authors. Review by the EPA Guidance Committee and EPA Board led to two additional recommendations (on immigrant mental healthcare and parity of mental and physical healthcare funding).
Although quality assurance (measures to keep a certain degree of quality), quality control and monitoring (applying quality indicators to the current degree of quality), and quality management (coordinated measures and activities with regard to quality) are conceptually distinct, in practice they are frequently used as if identical and hardly separable. There is a dearth of controlled trials addressing ways to optimize quality assurance in mental healthcare. Altogether, seventeen recommendations were developed addressing a range of aspects of quality assurance in mental healthcare, which appear usable across Europe. These were divided into recommendations about structures, processes and outcomes. Each recommendation was assigned to a hierarchical level of analysis (macro-, meso- and micro-level).
There was a lack of evidence retrievable by a systematic literature search about quality assurance of mental healthcare. Therefore, only after further topics and search had been added it was possible to develop recommendations with mostly medium evidence levels.
Evidence-based graded recommendations for quality assurance in mental healthcare were developed which should next be implemented and evaluated for feasibility and validity in some European countries. Due to the small evidence base identified corresponding to the practical obscurity of the concept and methods, a European research initiative is called for by the stakeholders represented in this Guidance to improve the educational, methodological and empirical basis for a future broad implementation of measures for quality assurance in European mental healthcare.
There is limited published data from long-term pediatric bipolar clinical trials with which to guide appropriate treatment decisions. Long-term efficacy and safety of aripiprazole was investigated in this patient population.
296 youths, ages 10-17 year-old with a DSM-IV diagnosis of bipolar I disorder were randomized to receive either placebo or aripiprazole (10mg or 30mg) in a 4-week double-blind trial. Completers continued assigned treatments for an additional 26 weeks (double-blind). Efficacy endpoints included mean change from baseline to week 4 and week 30 on the Young Mania Rating Scale; Children's Global Assessment Scale, Clinical Global Impressions-Bipolar version severity scale, General Behavior Inventory, Attention Deficit Hyperactivity Disorders Rating Scale, and time to discontinuation. Tolerability/safety assessments included incidence and severity of AEs, blood chemistries and metabolic parameters.
Over the 30-week course of double-blind treatment, aripiprazole (10 mg and 30 mg) was superior to placebo as early as week 1 (p< 0.002) and at all scheduled visits from week 2 through week 30 on mean change from baseline in the Y-MRS total score (p<.0001; all visits). Significant improvements were observed on multiple endpoints including the CGAS, GBI, CGI-BP, ADHD-RS-IV total score, time to discontinuation, and response and remission rates. The 3 most common AEs were somnolence, extrapyramidal disorder, and fatigue. Mean change in body weight z-scores over 30 weeks was not clinically significant.
Over 30-weeks of treatment, both doses of aripiprazole were superior to placebo in the long term treatment of pediatric bipolar patients. Aripiprazole was generally well tolerated.
The Health Utilities Index-Mark 2 (HUI2), a generic instrument for assessing health status, is an important effectiveness input for pharmacoeconomic modelling. It has not previously been used in patients with attention deficit/hyperactivity disorder (ADHD).
To use HUI2 to assess health utility in patients aged 6–17 years with ADHD receiving the prodrug stimulant lisdexamfetamine dimesylate (LDX).
SPD489-325 was a 7-week, randomized, double-blind, placebo-controlled trial of LDX, with osmotic-release oral system methylphenidate (OROSMPH) as a reference treatment. Patients’ parents or guardians completed HUI2 questionnaires at baseline and weeks 4 and 7. Utilities were estimated for treatment responders and non-responders, with response defined as a Clinical Global Impressions-Improvement (CGI-I) score of 1 or 2, or a ≥25% or ≥30% reduction in ADHD Rating Scale IV (ADHD-RS-IV) total score.
Of 336 patients randomized, 317 were included in the full analysis set (LDX, n=104; OROS-MPH, n=107; placebo, n=106) and 196 completed the study. At endpoint, mean HUI2 utility scores across all treatment groups were higher for responders than non-responders when response was based on CGI-I score (responders: 0.896 [SD, 0.0990]; non-responders: 0.838 [0.1421]), on a ≥25% reduction in ADHD-RS-IV score from baseline (responders, 0.899 [0.0969]; non-responders, 0.809 [0.1474]), or on a ≥30% reduction in ADHD-RS-IV score from baseline (responders, 0.902 [0.0938]; non-responders 0.814 [0.1477]).
The HUI2 instrument is sensitive to treatment response in the child and adolescent ADHD patient population. Health utilities generated using HUI2 are therefore suitable for cost effectiveness evaluations of ADHD medications.
GXR, a selective α2A-adrenergic agonist, is a non-stimulant treatment for ADHD (approved in the USA for children and adolescents and in Canada for children).
To assess the efficacy (symptoms and function) and safety of dose-optimized GXR compared with placebo in children and adolescents with ADHD.
To evaluate the efficacy (symptom and function) and safety of GXR for the treatment of ADHD. An atomoxetine (ATX) arm was included to provide reference data against placebo (NCT01244490).
Patients (6–17 years) were randomly assigned at baseline to dose-optimized GXR (6–12 years, 1–4 mg/day; 13–17 years, 1–7 mg/day), ATX (10–100mg/day) or placebo for 4 or 7 weeks. The primary efficacy measure is change from baseline in ADHD-Rating Scale-version IV (ADHD-RS-IV). Key secondary measures were defined as Clinical Global Impressions-Improvement (CGI-I) and the Weiss Functional Impairment Rating Scale-Parent (WFIRS-P). Safety assessments included treatment-emergent adverse events (TEAEs), electrocardiograms, and vital signs.
Of 338 patients randomized, 272 (80.5%) completed the study. Placebo-adjusted differences in least squares (LS) mean in ADHD-RS-IV total score, percent improvement versus placebo for CGI-I, placebo-adjusted differences in LS mean change from baseline in WFIRS-P score (family and learning and school domains) are shown in the Table. The most common TEAEs for GXR were somnolence, headache, and fatigue; 8 (7%) TEAEs were severe.
GXR was effective and well tolerated in children and adolescents with ADHD.
Placebo-adjusted difference in LS mean change from baseline in ADHD-RS-IV total score (95% Cl, p-value; effect size)
−8.9 (−11.9, −5.8, p<0.001; 0.76)
−3.8 (−6.8, −0.7, p<0.05; 0.32)
Difference in improvement from placebo for CGI-I (95% Cl, p-value)
23.7% (11.1, 36.4; p<0.001)
12.1% (−0.9, 25.1; p<0.05)
Placebo-adjusted difference in LS mean change from baseline in WFIRS-P; learning and school domain score (95%CI, p-value; effect size)
−0.22 (−0.36, −0.08, p<0.01; 0.42)
−0.16 (−0.31, −0.02, p<0.05; 0.32)
Placebo-adjusted difference in LS mean change from baseline in WFIRS-P; family domain score (95%CI, p-value; effect size)
Evaluate the efficacy and long-term safety of investigational aripiprazole once-monthly (ARI-OM) for maintenance treatment in schizophrenia.
Patients requiring chronic treatment for schizophrenia, not on aripiprazole monotherapy, were cross-titrated from other antipsychotic(s) to aripiprazole in an oral conversion phase (Phase 1). All patients entered an oral aripiprazole stabilization phase (Phase 2). Patients meeting stability criteria entered an ARI-OM stabilization phase (Phase 3), with coadministration of oral aripiprazole for the first 2 weeks. Patients meeting stability criteria were randomized to ARI-OM or placebo once-monthly (placebo-OM) during a 52-week, double-blind maintenance phase (Phase 4). Primary endpoint was time-to-impending relapse. Safety and tolerability were also assessed.
710 patients entered Phase 2, 576 Phase 3 and 403 Phase 4 (ARI-OM=269, placebo-OM=134). The study was terminated early because efficacy was demonstrated by a pre-planned interim analysis. Time-to-impending relapse was significantly delayed with ARI-OM vs. placebo-OM (p< 0.0001, log-rank test). Discontinuations due to treatment-emergent adverse events (AEs) were: Phase 1, 3.8% (n=24/632); Phase 2, 3.0% (n=21/709); Phase 3, 4.9% (n=28/576); Phase 4, 7.1% (n=19/269). Most AEs were mild or moderate. Insomnia was the only AE >5% incidence in any phase. Headache, somnolence, and nausea had a peak first onset within the first 4 weeks of treatment. There were no unusual shifts in all phases in laboratory values, fasting metabolic parameters, weight, or objective scales of movement disorders.
ARI-OM significantly delayed time-to-impending relapse compared with placebo-OM and was well tolerated as maintenance treatment in schizophrenia1.
Schizophrenia is a serious mental illness that carries a significant burden for families providing care.
The ADHES carers' survey canvassed opinions of families/friends of patients with schizophrenia across Europe.
To ascertain carer attitudes towards schizophrenia, its treatment and treatment adherence.
The survey was conducted from January-April 2011 in 16 European countries, comprising 10 questions relating to the respondents' understanding of schizophrenia, attitudes towards schizophrenia treatments, and perception of the family's/friend's role in supporting patients with schizophrenia.
Results were obtained from 138 respondents. 76% of carers recognized the importance of medication to help patients get better, improve their quality of life (77%) and relationships (74%). 67% of carers responded that they believed schizophrenia treatment damages patients' general health. Two-thirds of the carers reported that treatment adherence was a burden for the patient and over a third of carers indicated that it was a daily struggle to get patients to take their medication. 50% of carers considered the benefits offered by long-acting injectable antipsychotics as very/quite important and thus, could provide a valuable tool in improving treatment adherence. 92% of carers agreed on the importance of family support to boost treatment adherence with education/information deemed important for families and patients alike.
Carers recognize the issues they face in caring for patients with schizophrenia and their role in improving partial/non-adherence to medication, especially to avoid suboptimal treatment outcomes. The important role of family carers should be considered by healthcare professionals when treating patients with schizophrenia.
GXR, a selective α2A-adrenergic agonist, is a non-stimulant ADHD treatment approved in the USA for children and adolescents, and in Canada for children.
To evaluate long-term maintenance of efficacy of GXR in children and adolescents with ADHD who respond to an initial open-label, short-term trial.
To determine if there is a higher rate of treatment failure for placebo vs GXR during the double-blind randomised-withdrawal phase (RWP) (NCT01081145).
Patients (6–17 years) meeting DSM-IV-TR criteria for ADHD, baseline ADHD Rating Scale-IV (ADHD-RS-IV) ≥32 and Clinical Global Impressions-Severity (CGI-S) ratings ≥4 were enrolled. Following 7-week dose optimization and 6-week maintenance periods on open-label GXR (1–7 mg/day), eligible patients entered a 26-week, double-blind, RWP with GXR or placebo. The primary endpoint was rate of treatment failure (≥50% increase in ADHD-RS-IV total score and ≥2-point increase in CGI-S at two consecutive visits, compared to the RWP baseline). The key secondary endpoint was time-to-treatment failure. Safety assessments included treatment-emergent adverse events (TEAEs), electrocardiograms and vital signs.
Of 528 patients enrolled, 316 (60.0%) entered the RWP. At study end, 49.3% (GXR) and 64.9% (placebo) (95%CI; −26.6, −4.5, p<0.01) of patients had relapsed (Figure). Time-to-treatment failure was 56 days (placebo) versus 218 days (GXR), p=0.003. During the RWP, the most common GXR TEAEs (≥5% patients) were headache, somnolence and nasopharyngitis.
GXR demonstrated long-term maintenance of efficacy versus placebo in children and adolescents with ADHD.
Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.
We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.
In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).
AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.