Suicide and Psychosis: Results From a Population-Based Cohort of Suicide Death (N = 4380)

2021 ◽  
Author(s):  
Anna R Docherty ◽  
Amanda V Bakian ◽  
Emily DiBlasi ◽  
Andrey A Shabalin ◽  
Danli Chen ◽  
...  
Keyword(s):  
Genetic Risk ◽  
Large Population ◽  
Population Based ◽  
Suicide Death ◽  
Genetics Research ◽  
Affective Symptoms ◽  
Genome Wide ◽  
Increased Risk ◽  
Genetic Risks ◽  
Genome Wide Data

Abstract Approximately 5% of individuals with schizophrenia die from suicide. However, suicide in psychosis is still poorly characterized, partly due to a lack of adequate population-based clinical or genetic data on suicide death. The Utah Suicide Genetics Research Study (USGRS) provides a large population-based cohort of suicide deaths with medical record and genome-wide data (N = 4380). Examination of this cohort identified medical and genetic risks associated with type of suicide death and investigated the relative contributions of psychotic and affective symptoms to method of suicide. Key differences in method of suicide (common vs. atypical methods) were tested in relation to lifetime psychosis and genome-wide genetic risk for schizophrenia, major depressive disorder, and neuroticism. Consistent with previous studies, psychosis-spectrum disorders were observed to be common in suicide (15% of the cohort). Individuals with psychosis more frequently died from atypical methods, with rates of atypical suicide increasing across the schizophrenia spectrum. Genetic risk for schizophrenia was also associated with atypical suicide, regardless of clinical diagnosis, though this association weakened when filtering individuals with schizophrenia from the analysis. Follow-up examination indicated that high rates of atypical suicide observed in schizophrenia are not likely accounted for by restricted access to firearms. Overall, better accounting for the increased risk of atypical suicide methods in psychosis could lead to improved prevention strategies in a large portion of the suicide risk population.

scholarly journals Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting

Neurology ◽  
2019 ◽  
Vol 92 (5) ◽  
pp. e486-e503 ◽  
Author(s):  
Ganesh Chauhan ◽  
Hieab H.H. Adams ◽  
Claudia L. Satizabal ◽  
Joshua C. Bis ◽  
Alexander Teumer ◽  
...  
Keyword(s):  
Risk Factors ◽  
Genetic Risk ◽  
Association Studies ◽  
Large Population ◽  
Population Based ◽  
Genome Wide Association Studies ◽  
Lifestyle Risk Factors ◽  
Brain Infarcts ◽  
Genome Wide ◽  
Lifestyle Risk

ObjectiveTo explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts.MethodsWe performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n = 20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI.ResultsThe mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 × 10−8; and LINC00539/ZDHHC20, p = 5.82 × 10−9. Both have been associated with blood pressure (BP)–related phenotypes, but did not replicate in the smaller follow-up sample or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits (p value for BI, p[BI] = 9.38 × 10−25; p[SSBI] = 5.23 × 10−14 for hypertension), smoking (p[BI] = 4.4 × 10−10; p[SSBI] = 1.2 × 10−4), diabetes (p[BI] = 1.7 × 10−8; p[SSBI] = 2.8 × 10−3), previous cardiovascular disease (p[BI] = 1.0 × 10−18; p[SSBI] = 2.3 × 10−7), stroke (p[BI] = 3.9 × 10−69; p[SSBI] = 3.2 × 10−24), and MRI-defined white matter hyperintensity burden (p[BI] = 1.43 × 10−157; p[SSBI] = 3.16 × 10−106), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI (p ≤ 0.0022), without indication of directional pleiotropy.ConclusionIn this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI.

scholarly journals Subthreshold psychosis symptoms associated with molecular genetic risk in a population-based cohort: Findings from Generation Scotland

2019 ◽  
Author(s):  
A.R. Docherty ◽  
Andrey A. Shabalin ◽  
Daniel E. Adkins ◽  
Frank Mann ◽  
Robert F. Krueger ◽  
...  
Keyword(s):  
Sex Differences ◽  
General Population ◽  
Genetic Risk ◽  
Molecular Genetic ◽  
Population Based ◽  
Risk Scores ◽  
Factor Scores ◽  
Polygenic Risk ◽  
Genome Wide ◽  
Genetic Risks

AbstractImportanceSubthreshold psychosis symptoms in the general population may be associated with genetic risk for schizophrenia. In this analysis, empirically-derived symptom factor scores led to a detection of significant and robust polygenic signal.ObjectiveThis study sought to optimize genetic association with data-driven symptom factor scores, accounting for cohort factor structure and sex differences.DesignEFA-derived symptom factor scores were regressed onto PRS for schizophrenia in models accounting for age and genetic ancestry principal components. Follow-up examination of symptom factor score associations with other related genetic risks included ADHD, autism, bipolar disorder, major depression, and neuroticism.ParticipantsThis study examined the newly expanded symptom dataset from the Northern European ancestry cohort, Generation Scotland: Scottish Family Health Study (N = 9,105 individuals 18-65 years of age) comprising common variant and subthreshold psychosis symptom data. A total of 5,391 females and 3,713 males with age M[SD] = 45.2 [13] were included in the final analyses.Main Outcome and MeasureSubthreshold psychosis symptoms were measured using the Schizotypal Personality Questionnaire-Brief (SPQ-B). Primary phenotypic factor scores and genome-wide polygenic risk scores (PRS) reflected weighted sum scores and were examined as continuous measures. Polygenic risk scores were calculated from genome-wide association summary statistics using 7,358,674 imputed common genetic variants passing quality control.ResultsIn males, symptom factor scores were positively associated with polygenic risk for schizophrenia alone and implicated primarily interpersonal/negative symptoms. In females, symptom factor scores were positively associated with polygenic risks for ADHD and autism but not schizophrenia. Scores were robustly associated with genetic risk for neuroticism across both males and females.Conclusions and RelevanceThis study detected a significant association of subthreshold psychosis symptoms with genetic risk for schizophrenia and neuroticism in a population-based sample. Furthermore, important sex differences suggest a need for better understanding of schizophrenia risk assessment in females.Key PointsQuestionWhat molecular genetic risks are associated with subthreshold psychosis symptoms in the general population?FindingsIn a large population-based cohort (N = 9,084), significant associations of polygenic risks with symptoms were observed. Symptoms were associated with genetic risk for schizophrenia in males, for ADHD and autism spectrum disorder in females, and for neuroticism across both males and females.MeaningAssociations of genetic risk with symptoms in the general population are highly significant and suggest important sex differences.

scholarly journals Joint association between education and polygenic risk score for incident coronary heart disease events: a longitudinal population-based study of 26 203 men and women

2021 ◽  
pp. jech-2020-214358
Author(s):  
Pekka Martikainen ◽  
Kaarina Korhonen ◽  
Aline Jelenkovic ◽  
Hannu Lahtinen ◽  
Aki Havulinna ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Risk Score ◽  
Density Lipoprotein ◽  
Population Based ◽  
Polygenic Risk Score ◽  
Genome Wide ◽  
Increased Risk ◽  
Region Of Residence

BackgroundGenetic vulnerability to coronary heart disease (CHD) is well established, but little is known whether these effects are mediated or modified by equally well-established social determinants of CHD. We estimate the joint associations of the polygenetic risk score (PRS) for CHD and education on CHD events.MethodsThe data are from the 1992, 1997, 2002, 2007 and 2012 surveys of the population-based FINRISK Study including measures of social, behavioural and metabolic factors and genome-wide genotypes (N=26 203). Follow-up of fatal and non-fatal incident CHD events (N=2063) was based on nationwide registers.ResultsAllowing for age, sex, study year, region of residence, study batch and principal components, those in the highest quartile of PRS for CHD had strongly increased risk of CHD events compared with the lowest quartile (HR=2.26; 95% CI: 1.97 to 2.59); associations were also observed for low education (HR=1.58; 95% CI: 1.32 to 1.89). These effects were largely independent of each other. Adjustment for baseline smoking, alcohol use, body mass index, igh-density lipoprotein (HDL) and total cholesterol, blood pressure and diabetes attenuated the PRS associations by 10% and the education associations by 50%. We do not find strong evidence of interactions between PRS and education.ConclusionsPRS and education predict CHD events, and these associations are independent of each other. Both can improve CHD prediction beyond behavioural risks. The results imply that observational studies that do not have information on genetic risk factors for CHD do not provide confounded estimates for the association between education and CHD.

scholarly journals Melanoma is associated with an increased risk of bullous pemphigoid: a large population-based longitudinal study

2021 ◽  
Author(s):  
Khalaf Kridin ◽  
Jennifer E. Hundt ◽  
Ralf J. Ludwig ◽  
Kyle T. Amber ◽  
Dana Tzur Bitan ◽  
...  
Keyword(s):  
Bullous Pemphigoid ◽  
Statistical Significance ◽  
Large Population ◽  
Underlying Mechanism ◽  
Population Based ◽  
Control Subjects ◽  
Increased Risk ◽  
Bidirectional Association ◽  
History Of ◽  
Incident Cases

AbstractThe association between bullous pemphigoid (BP) and melanoma is yet to be investigated. We aimed to assess assess the bidirectional association between BP and melanoma and to delineate the epidemiological features of patients with both diagnoses. A population-based cohort study was performed comparing BP patients (n = 3924) with age-, sex- and ethnicity-matched control subjects (n = 19,280) with regard to incident cases of melanoma. A case–control design was additionally adopted to estimate the risk of BP in individuals with a preexisting diagnosis of melanoma. The prevalence of preexisting melanoma was higher in patients with BP than in control subjects (1.5% vs. 1.0%, respectively; P = 0.004). A history of melanoma confers a 50% increase in the risk of subsequent BP (OR 1.53; 95% CI 1.14–2.06). This risk was higher among males (OR 1.66; 95% CI 1.09–2.54) and individuals older than 80 years (OR 1.63; 95% CI 1.11–2.38), and persisted after adjustment for multiple putative confounders including PD-1/PDL-1 antagonists (adjusted OR 1.53; 95% CI 1.14–2.06). Conversely, the risk of melanoma among patients with BP was slightly elevated, but did not reach the level of statistical significance (adjusted HR 1.13; 95% CI 0.73–1.74). Patients with a dual diagnosis of BP and melanoma were older at the onset of BP and had lower body mass index. A history of melanoma is associated with a 50% increase in the incidence of subsequent BP. Physicians managing patients with both conditions should be aware of this association. Further research is warranted to reveal the underlying mechanism of these findings.

scholarly journals Adjuvant Hormonotherapy and Cardiovascular Risk in Post-Menopausal Women with Breast Cancer: A Large Population-Based Cohort Study

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2254
Author(s):  
Matteo Franchi ◽  
Roberta Tritto ◽  
Luigi Tarantini ◽  
Alessandro Navazio ◽  
Giovanni Corrao
Keyword(s):  
Breast Cancer ◽  
Heart Failure ◽  
Adjuvant Therapy ◽  
Large Population ◽  
Positive Association ◽  
Population Based ◽  
Study Cohort ◽  
Increased Risk ◽  
Post Menopausal ◽  
New Diagnosis

Background: Whether aromatase inhibitors (AIs) increase the risk of cardiovascular (CV) events, compared to tamoxifen, in women with breast cancer is still debated. We evaluated the association between AI and CV outcomes in a large population-based cohort of breast cancer women. Methods: By using healthcare utilization databases of Lombardy (Italy), we identified women ≥50 years, with new diagnosis of breast cancer between 2009 and 2015, who started adjuvant therapy with either AI or tamoxifen. We estimated the association between exposure to AI and CV outcomes (including myocardial infarction, ischemic stroke, heart failure or any CV event) by a Cox proportional hazard model with inverse probability of treatment and censoring weighting. Results: The study cohort included 26,009 women starting treatment with AI and 7937 with tamoxifen. Over a median follow-up of 5.8 years, a positive association was found between AI and heart failure (Hazard Ratio = 1.20, 95% CI: 1.02 to 1.42) and any CV event (1.14, 1.00 to 1.29). The CV risk increased in women with previous CV risk factors, including hypertension, diabetes and dyslipidemia. Conclusions: Adjuvant therapy with AI in breast cancer women aged more than 50 years is associated with increased risk of heart failure and combined CV events.

scholarly journals Self-reported goiter is associated with a significantly increased risk of gastric noncardia adenocarcinoma in a large population-based Chinese cohort

2006 ◽  
Vol 119 (6) ◽  
pp. 1508-1510 ◽  
Author(s):  
Christian C. Abnet ◽  
Jin-Hu Fan ◽  
Farin Kamangar ◽  
Xiu-Di Sun ◽  
Philip R. Taylor ◽  
...  
Keyword(s):  
Large Population ◽  
Population Based ◽  
Increased Risk ◽  
Chinese Cohort

scholarly journals Sleep problems increase the risk of musculoskeletal pain in boys but not girls: a prospective cohort study

2020 ◽  
Vol 179 (11) ◽  
pp. 1711-1719
Author(s):  
Alessandro Andreucci ◽  
Paul Campbell ◽  
Lisa K Mundy ◽  
Susan M Sawyer ◽  
Silja Kosola ◽  
...  
Keyword(s):  
Cohort Study ◽  
Musculoskeletal Pain ◽  
Prospective Cohort Study ◽  
Prospective Cohort ◽  
Sleep Problems ◽  
Large Population ◽  
Population Based ◽  
School Aged Children ◽  
Increased Risk ◽  
One Year

Abstract Adults with sleep problems are at higher risk for onset of musculoskeletal pain, but the evidence is less clear for children. This prospective cohort study investigated whether children with sleep problems are at higher risk for onset of musculoskeletal pain and explored whether sex is a modifier of this association. In a prospective cohort study of Australian schoolchildren (n = 1239, mean age 9 years), the associations between sleep problems at baseline and new onset of both musculoskeletal pain and persistent musculoskeletal pain (pain lasting > 3 months) 1 year later were investigated using logistic regression. The potential modifying effect of sex was also assessed. One-year incidence proportion for musculoskeletal pain onset is 43% and 7% for persistent musculoskeletal pain. Sleep problems were associated with musculoskeletal pain onset and persistent musculoskeletal pain onset in boys, odds ratio 2.80 (95% CI 1.39, 5.62) and OR 3.70 (1.30, 10.54), respectively, but not girls OR 0.58 (0.28, 1.19) and OR 1.43 (0.41, 4.95), respectively. Conclusions: Rates of musculoskeletal pain are high in children. Boys with sleep problems are at greater risk of onset of musculoskeletal pain, but girls do not appear to have higher risk. Consideration of sleep health may help prevent persistent musculoskeletal pain in children. What is Known:• Sleep problems are associated with the onset of musculoskeletal pain in adults.• It is not clear if the association between sleep problems and the onset of musculoskeletal pain is present also in children and if sex plays a role in this association. What is New:• This is the first large population-based study that has prospectively investigated the relationship between sleep problems and onset of musculoskeletal pain in school-aged children.• Children, especially boys with sleep problems, were at increased risk for the development of persistent musculoskeletal pain.

scholarly journals Insights into Dyslexia Genetics Research from the Last Two Decades

2021 ◽  
Vol 12 (1) ◽  
pp. 27
Author(s):  
Florina Erbeli ◽  
Marianne Rice ◽  
Silvia Paracchini
Keyword(s):  
Language Disorder ◽  
Association Studies ◽  
Neurodevelopmental Disorder ◽  
Molecular Genetic ◽  
Genetic Research ◽  
Twin Studies ◽  
Genome Wide Association Studies ◽  
Genetics Research ◽  
Genome Wide ◽  
Genetic Risks

Dyslexia, a specific reading disability, is a common (up to 10% of children) and highly heritable (~70%) neurodevelopmental disorder. Behavioral and molecular genetic approaches are aimed towards dissecting its significant genetic component. In the proposed review, we will summarize advances in twin and molecular genetic research from the past 20 years. First, we will briefly outline the clinical and educational presentation and epidemiology of dyslexia. Next, we will summarize results from twin studies, followed by molecular genetic research (e.g., genome-wide association studies (GWASs)). In particular, we will highlight converging key insights from genetic research. (1) Dyslexia is a highly polygenic neurodevelopmental disorder with a complex genetic architecture. (2) Dyslexia categories share a large proportion of genetics with continuously distributed measures of reading skills, with shared genetic risks also seen across development. (3) Dyslexia genetic risks are shared with those implicated in many other neurodevelopmental disorders (e.g., developmental language disorder and dyscalculia). Finally, we will discuss the implications and future directions. As the diversity of genetic studies continues to increase through international collaborate efforts, we will highlight the challenges in advances of genetics discoveries in this field.

scholarly journals Blood Neutrophil Counts are Associated with Exacerbation Frequency and Mortality in COPD

2020 ◽  
Author(s):  
Mike Lonergan ◽  
Alison J Dicker ◽  
Megan L Crichton ◽  
Holly R Keir ◽  
Melissa K. Van Dyke ◽  
...  
Keyword(s):  
Large Population ◽  
Real Life ◽  
Population Based ◽  
Blood Eosinophil ◽  
Blood Neutrophil ◽  
Disease Heterogeneity ◽  
Disease Information ◽  
Increased Risk ◽  
Eosinophil Counts

Abstract Background Identifying patients with COPD at increased risk of poor outcomes is challenging due to disease heterogeneity. Potential biomarkers need to be readily available in real-life clinical practice. Blood eosinophil counts are widely studied but few studies have examined the prognostic value of blood neutrophil counts (BNC). Methods In a large population-based COPD registry in the East of Scotland (TARDIS: Tayside Allergic and Respiratory Disease Information System), BNC were compared to measures of disease severity and mortality over up to 15 years follow-up. Potential mechanisms of disease modification by BNC were explored in a nested microbiome substudy. Results 178120 neutrophil counts were obtained from 7220 people (mean follow up 9 years) during stable disease periods. Median BNC was 5200cells/µL (IQR 4000-7000cells/µL). Mortality rates among those 34% with elevated BNCs (defined as 6000-15000cells/µL) at the study start were 80% higher (14.0/100 person years v 7.8/100py, P<0.001) than those with BNC in the normal range (2000-6000cells/µL). People with elevated BNC were more likely to be classified as GOLD D (46% v 33% P<0.001), have more exacerbations (mean 2.3 v 1.3/year, P<0.001), and were more likely to have severe exacerbations (13% vs. 5%, P<0.001) in the following year. Eosinophil counts were much less predictive of these outcomes. In a sub-cohort (N=276), patients with elevated BNC had increased relative abundance of Proteobacteria and reduced microbiome diversity. Conclusion High BNC may provide a useful indicator of risk of exacerbations and mortality in COPD patients.

scholarly journals Hypermethylation of the VTRNA2-1 promoter in maternal blood is associated with preterm birth

2020 ◽  
Author(s):  
Young-Ah You ◽  
Eun Jin Kwon ◽  
Han-Sung Hwang ◽  
Suk-Joo Choi ◽  
Sae Kyung Choi ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Large Population ◽  
Underlying Mechanism ◽  
Maternal Blood ◽  
Blood Cell Count ◽  
Genome Wide ◽  
Increased Risk ◽  
Health And Disease ◽  
Whole Blood Cells ◽  
Dna Methylation Analysis

Abstract Background: Preterm birth is associated with an increased risk of neonatal complications and death, as well as poor health and disease later in life. Epigenetics could contribute to the mechanism underlying preterm birth. Results: Genome-wide DNA methylation analysis of whole blood cells from ten women was performed using an Illumina Infinium HumanMethylation450 BeadChips array. We identified 1,581 differentially methylated CpG sites in promotor regions between term and preterm birth. Although the differences were not significant after correcting for multiple tests, seven CpGs on the genomically imprinted VTRNA2-1 showed the largest differences (range: 26–39%). Pyrosequencing verification was performed with blood samples from pregnant women recruited additionally (n = 82). In total, 28 (34.1%) cases showed hypomethylation of the VTRNA2-1 promoter (< 13% methylation), while 54 cases (65.9%) showed a methylation level of 30–60%. Hypermethylation of VTRNA2-1 was associated with an increased risk of preterm birth after adjusting for maternal age, season of delivery, parity and white blood cell count. The mRNA expression of VTRNA2-1 was 0.51-fold lower in women with preterm deliveries (n = 20) compared with women with term deliveries (n = 20). Conclusions: Our results suggest that changes in VTRNA2-1 methylation in maternal blood are related to preterm birth. Further studies are needed to confirm the association of VTRNA2-1 methylation with preterm birth in a large population, and to elucidate the underlying mechanism.

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