Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Barriers to oral care: a cross-sectional analysis of the Canadian longitudinal study on aging (CLSA)

Abstract Background Oral health plays a role in overall health, indicating the need to identify barriers to accessing oral care. The objective of this study was to identify barriers to accessing oral health care and examine the association between socioeconomic, psychosocial, and physical measures with access to oral health care among older Canadians. Methods A cross-sectional study was conducted using data from the Canadian Longitudinal Study on Aging (CLSA) follow-up 1 survey to analyze dental insurance and last oral health care visit. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between socioeconomic, psychosocial, and physical measures with access to oral care, measured by dental insurance and last oral health visit. Results Among the 44,011 adults included in the study, 40% reported not having dental insurance while 15% had not visited an oral health professional in the previous 12 months. Several factors were identified as barriers to accessing oral health care including, no dental insurance, low household income, rural residence, and having no natural teeth. People with an annual income of <$50,000 were four times more likely to not have dental insurance (adjusted OR: 4.09; 95$100,000. Conclusions Identifying barriers to oral health care is important when developing public health strategies to improve access, however, further research is needed to identify the mechanisms as to why these barriers exist

Oral Health Problems among Canadians Aged 45 to 85: Data from the Canadian Longitudinal Study on Aging Baseline Survey (2011–2015)

Oral health is a critical component of overall health. The objective of this study was to describe oral health problems among 47,581 adults aged 45 to 85 in the Canadian Longitudinal Study on Aging (CLSA) among those who have at least one natural tooth (92%) and those without natural teeth across various demographic categories. Among the 47,581 participants in the study, 92% reported having at least one natural tooth (dentate). Among those without teeth, 63% reported an income less than CAD 50,000 versus 39% among those with teeth. Whether they had teeth or not, over 30% of people reported two or more oral health problems. Older adults appear to be retaining their natural teeth (28.9%), but still report experiencing oral health problems. As the population ages, loss of all teeth may not be the most useful proxy for poor oral health, and a population-level understanding of oral health problems may help to better define poor oral health

Trajectories of physical activity, from young adulthood to older adulthood, and pancreatic cancer risk; a population-based case-control study in Ontario, Canada

Abstract Background There is inconsistent evidence on the association between physical activity and pancreatic cancer risk and few studies have investigated early life or life-course physical activity. The objective of this study was to evaluate the association between trajectories of physical activity across the life-course and pancreatic cancer risk. Methods A population-based case-control study was conducted (2011–2013) using cases (n = 315) from the Ontario Pancreas Cancer Study and controls (n = 1254) from the Ontario Cancer Risk Factor Study. Self-reported recall of moderate and vigorous physical activity was measured at three time points: young adulthood (20s–30s), mid-adulthood (40s–50s) and older-adulthood (1 year prior to questionnaire completion). Physical activity trajectories were identified using latent class analysis. Odds ratios (OR) and 95% confidence intervals (CI) were estimated from multivariable logistic regression adjusted for covariates: age, sex, race, alcohol, smoking, vegetable, fruit and meat consumption, and family history of pancreatic cancer. Results Six life-course physical activity trajectories were identified: inactive at all ages (41.2%), low activity at all ages (31.9%), increasingly active (3.6%), high activity in young adulthood with substantial decrease (13.0%), high activity in young adulthood with slight decrease (5.0%), and persistent high activity (5.3%). Compared to the inactive at all ages trajectory, the associations between each trajectory and pancreatic cancer after confounder adjustment were: low activity at all ages (OR: 1.11; 95% CI: 0.75, 1.66), increasingly active (OR: 1.11; 95% CI: 0.56, 2.21), high activity in young adulthood with substantial decrease in older adulthood (OR: 0.76; 95% CI: 0.47, 1.23), high activity in young adulthood with slight decrease in older adulthood (OR: 0.98; 95% CI: 0.62, 1.53), and persistently high activity (OR: 1.50; 95% CI: 0.86, 2.62). When time periods were evaluated separately, the OR for the association between high moderate activity in the 20s–30s and pancreatic cancer was 0.89 (95% CI: 0.64, 1.25) and some sex differences were observed. Conclusion Distinct life-course physical activity trajectories were identified, but there was no evidence that any of the trajectories were associated with pancreatic cancer. Future studies with larger sample sizes are needed to understand the associations between physical activity trajectories over the life-course and pancreatic cancer risk

The Association between Early Childhood and Later Childhood Sugar-Containing Beverage Intake: A Prospective Cohort Study

Sugar-containing beverages (SCBs) are a major source of sugar intake in children. Early life intake of SCBs may be a strong predictor of SCB intake later in life. The primary objective of this study was to evaluate if SCB intake (defined as 100% fruit juice, soda, and sweetened drinks) in early childhood (&le;2.5 years of age) was associated with SCB intake in later childhood (5&ndash;9 years of age). A prospective cohort study was conducted using data from the TARGet Kids! primary care practice network (n = 999). Typical daily SCB intake was measured by parent-completed questionnaires. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression. A total of 43% of children consumed &ge;0.5 cups/day of SCBs at &le;2.5 years and this increased to 64% by 5&ndash;9 years. Daily SCB intake, compared to no daily intake, at &le;2.5 years was significantly associated with SCB intake at 5&ndash;9 years (adjusted OR: 4.03; 95% CI: 2.92&ndash;5.55) and this association was much stronger for soda/sweetened drinks (adjusted OR: 12.83; 95% CI: 4.98, 33.0) than 100% fruit juice (OR: 3.61; 95% CI: 2.63&ndash;4.95). Other early life risk factors for SCB intake at 5&ndash;9 years were presence of older siblings, low household income, and shorter breastfeeding duration. Daily intake of SCBs in early childhood was strongly associated with greater SCB intake in later childhood. Early life may be an important period to target for population prevention strategies

Understanding the mental health and intention to leave of the public health workforce in Canada during the COVID-19 pandemic: A cross-sectional study

Abstract Background There is limited evidence about the mental health and intention to leave of the public health workforce in Canada during the COVID-19 pandemic. The objectives of this study were to determine the prevalence of burnout, symptoms of anxiety and depression, and intention to leave among the Canadian public health workforce, and associations with individual and workplace factors. Methods A cross-sectional study was conducted using data collected by a Canada-wide survey from November 2022 to January 2023, where participants reported sociodemographic and workplace factors. Mental health outcomes were measured using validated tools including the Oldenburg Burnout Inventory, the 7-item Generalized Anxiety Disorder scale, and the 2-item Patient Health Questionnaire to measure symptoms of depression. Participants were asked to report if they intended to leave their position in public health. Logistic regression was used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) for the associations between explanatory variables such as sociodemographic, workplace factors, and outcomes of mental health, and intention to leave public health. Results Among the 671 participants, the prevalence of burnout, and symptoms of depression and anxiety in the two weeks prior were 64%, 26%, and 22% respectively. 33% of participants reported they were intending to leave their public health position in the coming year. Across all outcomes, sociodemographic factors were largely not associated with mental health and intention to leave. However, an exception to this was that those with 16–20 years of work experience had higher odds of burnout (aOR = 2.16; 95% CI = 1.12–4.18) compared to those with ≤ 5 years of work experience. Many workplace factors were associated with mental health outcomes and intention to leave public health. Those who felt bullied, threatened, or harassed because of work had increased odds of depressive symptoms (aOR = 1.85; 95% CI = 1.28–2.68), burnout (aOR = 1.61; 95% CI = 1.16–2.23), and intention to leave (aOR = 1.64; 95% CI = 1.13–2.37). Conclusions During the COVID-19 pandemic, some of the public health workforce experienced negative impacts on their mental health. 33% of the sample indicated an intention to leave their role, which has the potential to exacerbate pre-existing challenges in workforce retention. Study findings create an impetus for policy and practice changes to mitigate risks to mental health and attrition to create safe and healthy working environments for public health workers during public health crises

Impact of disasters, including pandemics, on cardiometabolic outcomes across the life-course: a systematic review

Background Disasters are events that disrupt the daily functioning of a community or society, and may increase long-term risk of adverse cardiometabolic outcomes, including cardiovascular disease, obesity and diabetes. The objective of this study was to conduct a systematic review to determine the impact of disasters, including pandemics, on cardiometabolic outcomes across the life-course.Design A systematic search was conducted in May 2020 using two electronic databases, EMBASE and Medline. All studies were screened in duplicate at title and abstract, and full-text level. Studies were eligible for inclusion if they assessed the association between a population-level or community disaster and cardiometabolic outcomes ≥1 month following the disaster. There were no restrictions on age, year of publication, country or population. Data were extracted on study characteristics, exposure (eg, type of disaster, region, year), cardiometabolic outcomes and measures of effect. Study quality was evaluated using the Joanna Briggs Institute critical appraisal tools.Results A total of 58 studies were included, with 24 studies reporting the effects of exposure to disaster during pregnancy/childhood and 34 studies reporting the effects of exposure during adulthood. Studies included exposure to natural (n=35; 60%) and human-made (n=23; 40%) disasters, with only three (5%) of these studies evaluating previous pandemics. Most studies reported increased cardiometabolic risk, including increased cardiovascular disease incidence or mortality, diabetes and obesity, but not all. Few studies evaluated the biological mechanisms or high-risk subgroups that may be at a greater risk of negative health outcomes following disasters.Conclusions The findings from this study suggest that the burden of disasters extend beyond the known direct harm, and attention is needed on the detrimental indirect long-term effects on cardiometabolic health. Given the current COVID-19 pandemic, these findings may inform public health prevention strategies to mitigate the impact of future cardiometabolic risk.PROSPERO registration number CRD42020186074

Symptoms of depression and anxiety, and unmet healthcare needs in adults during the COVID-19 pandemic: a cross-sectional study from the Canadian Longitudinal Study on Aging

Abstract Background The COVID-19 pandemic disrupted access to healthcare services in Canada. Research prior to the pandemic has found that depression and anxiety symptoms were associated with increased unmet healthcare needs. The primary objective of this study was to examine if mental health was associated with perceived access to healthcare during the pandemic Methods A cross-sectional study was conducted using data from 23,972 participants (aged 50-96) in the Canadian Longitudinal Study on Aging COVID-19 Exit Survey (Sept-Dec 2020). We used logistic regression to estimate how the presence of depression and anxiety symptoms, defined using scores of ≥10 on the Center for Epidemiologic Studies Depression Scale and ≥10 on the Generalized Anxiety Disorder Scale, were associated with the odds of reporting: 1) challenges accessing healthcare, 2) not going to a hospital or seeing a doctor when needed, 3) experiencing barriers to COVID-19 testing. Models were adjusted for sex, age, region, urban/rural residence, racial background, immigrant status, income, marital status, work status, chronic conditions, and pre-pandemic unmet needs. Results The presence of depressive (aOR=1.96; 95% CI=1.82, 2.11) and anxiety symptoms (aOR=2.33; 95% CI=2.04, 2.66) compared to the absence of these symptoms were independently associated with higher odds of challenges accessing healthcare. A statistically significant interaction with sex suggested stronger associations in females with anxiety. Symptoms of depression (aOR=2.88; 95% CI=2.58, 3.21) and anxiety (aOR=3.05; 95% CI=2.58, 3.60) were also associated with increased odds of not going to a hospital or seeing a doctor when needed. Lastly, depressive (aOR=1.99; 95% CI=1.71, 2.31) and anxiety symptoms (aOR=2.01; 95% CI=1.58, 2.56) were associated with higher odds of reporting barriers to COVID-19 testing. There was no significantly significant interaction with sex for the latter two outcomes. Conclusion The presence of depression and anxiety symptoms were strongly associated with perceived unmet healthcare needs during the COVID-19 pandemic. Interventions to improve healthcare access for adults with depression and anxiety during the pandemic may be necessary

Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci

SummaryAnalysis of de novo CNVs (dnCNVs) from the full Simons Simplex Collection (SSC) (N = 2,591 families) replicates prior findings of strong association with autism spectrum disorders (ASDs) and confirms six risk loci (1q21.1, 3q29, 7q11.23, 16p11.2, 15q11.2-13, and 22q11.2). The addition of published CNV data from the Autism Genome Project (AGP) and exome sequencing data from the SSC and the Autism Sequencing Consortium (ASC) shows that genes within small de novo deletions, but not within large dnCNVs, significantly overlap the high-effect risk genes identified by sequencing. Alternatively, large dnCNVs are found likely to contain multiple modest-effect risk genes. Overall, we find strong evidence that de novo mutations are associated with ASD apart from the risk for intellectual disability. Extending the transmission and de novo association test (TADA) to include small de novo deletions reveals 71 ASD risk loci, including 6 CNV regions (noted above) and 65 risk genes (FDR ≤ 0.1)