Publications by authors named "John J Mcgrath"

Article Synopsis
  • The study analyzed the impact of alcohol control policies on health outcomes related to alcohol in Nordic countries from 1990 to 2019.
  • More restrictive alcohol policies were generally linked to lower levels of alcohol-attributed harm, especially in Sweden and Norway, while Denmark, with the least restrictive policies, had higher harm levels.
  • Findings suggest that while stricter policies can reduce alcohol-related disease burdens, other factors like sex and specific locations also play crucial roles, indicating that policy effectiveness is context-dependent.
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Importance: Research suggests an increase in mental disorder incidence in recent years, but this trend remains unexplained, and there is a lack of large studies based on a representative sample that investigate mental disorders over the full spectrum.

Objective: To explore sex- and age-specific incidence of any mental disorder and 19 specific disorders according to birth cohort and calendar period.

Design, Setting, And Participants: This was a population-based cohort study among 5 936 202 individuals aged 1 to 80 years living in Denmark at some point between January 1, 2004, and December 31, 2021.

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Article Synopsis
  • The study explores how genetic factors (polygenic scores or PGS) for psychiatric disorders affect the treatment trajectories of individuals with early-onset Major Depressive Disorder (MDD) in secondary care.
  • Researchers used data from a large Danish sample, analyzing 10,577 individuals diagnosed with MDD between ages 10-25 to identify different patterns of treatment over seven years.
  • Findings reveal specific associations between PGS for ADHD and anorexia with treatment trajectories, suggesting that while genetics may influence the path of depression treatment, the effects are small and not currently useful for predicting clinical outcomes.
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People with physical diseases are reported to be at elevated risk of subsequent mental disorders. However, previous studies have considered only a few pairs of conditions, or have reported only relative risks. This study aimed to systematically explore the associations between physical diseases and subsequent mental disorders.

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Mental disorders are leading causes of disability and premature death worldwide, partly due to high comorbidity with cardiometabolic disorders. Reasons for this comorbidity are still poorly understood. We leverage nation-wide health records and near-complete genealogies of Denmark and Sweden (n = 17 million) to reveal the genetic and environmental contributions underlying the observed comorbidity between six mental disorders and 15 cardiometabolic disorders.

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While it is known that vitamin D deficiency is associated with adverse bone outcomes, it remains unclear whether low vitamin D status may increase the risk of a wider range of health outcomes. We had the opportunity to explore the association between common genetic variants associated with both 25 hydroxyvitamin D (25OHD) and the vitamin D binding protein (DBP, encoded by the gene) with a comprehensive range of health disorders and laboratory tests in a large academic medical center. We used summary statistics for 25OHD and DBP to generate polygenic scores (PGS) for 66,482 participants with primarily European ancestry and 13,285 participants with primarily African ancestry from the Vanderbilt University Medical Center Biobank (BioVU).

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Mental disorders (MDs) are leading causes of disability and premature death worldwide, partly due to high comorbidity with cardiometabolic disorders (CMDs). Reasons for this comorbidity are still poorly understood. We leverage nation-wide health records and complete genealogies of Denmark and Sweden (n=17 million) to reveal the genetic and environmental contributions underlying the observed comorbidity between six MDs and 14 CMDs.

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Article Synopsis
  • - The study investigated the link between neonatal levels of complement proteins C3 and C4 and the risk of six mental disorders in a large sample of 68,768 newborns.
  • - Genome-wide association studies (GWAS) identified multiple genetic loci related to C3 and C4 concentrations, but overall, no major associations with mental disorders were found in the total sample.
  • - A notable finding was that higher C3 levels were linked to a lower risk of schizophrenia specifically in females, and C4 was associated with altered risk for five autoimmune disorders through Mendelian randomization.
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Article Synopsis
  • Education is crucial for economic stability and mental health, yet mental disorders can negatively impact educational achievement, indicating complex genetic relationships.* -
  • The study analyzed how polygenic risk scores for six mental disorders affect detailed educational outcomes in a large sample of nearly 80,000 individuals, focusing on school performance in language and mathematics.* -
  • Results showed that high genetic risk for ADHD correlated with lower grades, while higher genetic risks for anorexia and bipolar disorder linked to better grades, highlighting the varied genetic influences on academic performance.*
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Background: It has been proposed that cat ownership may be a risk-modifying factor for schizophrenia-related disorders and psychotic-like experiences (PLE). This study aimed to systematically review and meta-analyze publications that reported the relationship between cat ownership and schizophrenia-related outcomes.

Methodology: We searched Medline, Embase, CINAHL, Web of Science, and gray literature for publications between January 1, 1980, and May 30, 2023, regardless of geographical location and language.

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  • The study examines how socioeconomic position (SEP) influences the relationship between mental disorders and mortality rates, highlighting a lack of existing research on this topic.
  • Researchers utilized various databases to compile observational studies that link mental disorders to mortality rates, while considering different SEP levels and specific causes of death.
  • The results, based on data from over 4 million individuals, indicate that higher SEP is associated with lower overall and natural cause mortality among those with mental disorders, although it correlates with higher mortality from external causes.
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Vitamin D status-a complex trait influenced by environmental and genetic factors-is tightly associated with skin colour and ancestry. Yet very few studies have investigated the genetic underpinnings of vitamin D levels across diverse ancestries, and the ones that have, relied on small sample sizes, resulting in inconclusive results. Here, we conduct genome-wide association studies (GWAS) of 25 hydroxyvitamin D (25OHD)-the main circulating form of vitamin D-in 442,435 individuals from four broad genetically-determined ancestry groups represented in the UK Biobank: European (N = 421,867), South Asian (N = 9,983), African (N = 8,306) and East Asian (N = 2,279).

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Article Synopsis
  • People with physical diseases like cardiovascular issues, cancer, and neurodegenerative disorders are at a higher risk for major depressive disorder (MDD), and those with MDD also face increased risks for various physical diseases, creating a cycle of health challenges.
  • This comorbidity leads to worse health outcomes, higher treatment costs, and more complex clinical management due to overlapping symptoms and treatments, highlighting the need for integrated care approaches.
  • The text explores shared genetic and biological factors, social influences, and effective treatment strategies for managing both MDD and common physical diseases, emphasizing the importance of lifestyle interventions and collaborative care models.
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Proportional hazards models have been proposed to analyse time-to-event phenotypes in genome-wide association studies (GWAS). However, little is known about the ability of proportional hazards models to identify genetic associations under different generative models and when ascertainment is present. Here we propose the age-dependent liability threshold (ADuLT) model as an alternative to a Cox regression based GWAS, here represented by SPACox.

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Article Synopsis
  • The accuracy of polygenic scores (PGS) improves significantly with larger sample sizes, which can be difficult to obtain, but using genetically related traits can help expand these samples.
  • The study introduces a new method for creating multi-PGS from existing genome-wide association studies (GWAS) without needing to pick the most relevant studies individually.
  • The multi-PGS framework shows enhanced prediction accuracy, achieving up to a 9-fold increase for certain psychiatric disorders, and can also be applied to new biobanks and traits lacking prior GWAS data.
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Background: Information on the frequency and timing of mental disorder onsets across the lifespan is of fundamental importance for public health planning. Broad, cross-national estimates of this information from coordinated general population surveys were last updated in 2007. We aimed to provide updated and improved estimates of age-of-onset distributions, lifetime prevalence, and morbid risk.

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Article Synopsis
  • Depression is a prevalent psychiatric disorder and major global disability, and a study involving over 1.3 million people identified 243 genetic risk loci, with 64 being newly discovered, many linked to glutamate and GABA receptor genes targeted by antidepressant medications.
  • The research showed depression is highly polygenic, meaning it's influenced by many genetic variants, with about 11,700 variants accounting for 90% of heritability; many of these variants also affect other psychiatric disorders and educational outcomes.
  • The study highlighted genetic and clinical differences within depression subgroups, indicating those with a higher polygenic burden face significantly increased risks for recurrence and other mental health issues, with notable differences based on sex.
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Aims: We provide an overview of nationwide environmental data available for Denmark and its linkage potentials to individual-level records with the aim of promoting research on the potential impact of the local surrounding environment on human health.

Background: Researchers in Denmark have unique opportunities for conducting large population-based studies treating the entire Danish population as one big, open and dynamic cohort based on nationally complete population and health registries. So far, most research in this area has utilised individual- and family-level information to study the clustering of disease in families, comorbidities, risk of, and prognosis after, disease onset, and social gradients in disease risk.

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  • This study investigates the incidence rates and early diagnostic transitions among schizophrenia spectrum disorders in Denmark from 2000 to 2018.
  • The analysis used nationwide healthcare data to identify trends and pathways, revealing consistent incidence rates for schizophrenia but a decline for schizoaffective disorder and an increase for schizotypal disorder.
  • Most patients showed early diagnostic stability, but a notable percentage transitioned from schizophrenia or schizoaffective disorder to a diagnosis of schizotypal disorder.
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Introduction: Surveys and registers have provided important insights into the mental health of the community. However, both sources have strengths and limitations. While participation in surveys has been shown to be lower among those with mental disorders, misclassification and limited information on confounders are typical issues for registers.

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Background: Register-based studies of major depressive disorder (MDD) do not capture all prevalent cases, as untreated cases and diagnoses made by general practitioners are not recorded in the registers. We examined the prevalence and agreement of survey- and register-based measures of depression, and explored sociodemographic and health-related factors that may have influenced this agreement.

Methods: All 32,407 participants in the 2017 Central Denmark Region How are you? survey were linked to hospital and prescription records.

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Background: The most common treatment for major depressive disorder (MDD) is antidepressant medication (ADM). Results are reported on frequency of ADM use, reasons for use, and perceived effectiveness of use in general population surveys across 20 countries.

Methods: Face-to-face interviews with community samples totaling = 49 919 respondents in the World Health Organization (WHO) World Mental Health (WMH) Surveys asked about ADM use anytime in the prior 12 months in conjunction with validated fully structured diagnostic interviews.

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The vitamin D binding protein (DBP), encoded by the group-specific component (GC) gene, is a component of the vitamin D system. In a genome-wide association study of DBP concentration in 65,589 neonates we identify 26 independent loci, 17 of which are in or close to the GC gene, with fine-mapping identifying 2 missense variants on chromosomes 12 and 17 (within SH2B3 and GSDMA, respectively). When adjusted for GC haplotypes, we find 15 independent loci distributed over 10 chromosomes.

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