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BACKGROUND: Immune mechanisms are associated with adverse outcomes in schizophrenia; however, the predictive value of various peripheral immune biomarkers has not been collectively investigated in a large cohort before. OBJECTIVE: To investigate how white blood cell (WBC) counts, ratios, and C-Reactive Protein (CRP) levels influence the long-term outcomes of individuals with schizophrenia spectrum disorder (SSD). METHODS: We identified all adults in the Central Denmark Region during 1994-2013 with a measurement of WBC counts and/or CRP at first diagnosis of SSD. WBC ratios were calculated, and both WBC counts and ratios were quartile-categorized (Q4 upper quartile). We followed these individuals from first diagnosis until outcome of interest (death, treatment resistance and psychiatric readmissions), emigration or December 31, 2016, using Cox regression analysis to estimate adjusted hazard ratios (aHRs). RESULTS: Among 6,845 participants, 375 (5.5 %) died, 477 (6.9 %) exhibited treatment resistance, and 1470 (21.5 %) were readmitted during follow-up. Elevated baseline levels of leukocytes, neutrophils, monocytes, LLR, NLR, MLR, and CRP increased the risk of death, whereas higher levels of lymphocytes, platelets, and PLR were associated with lower risk. ROC analysis identified CRP as the strongest predictor for mortality (AUC=0.84). Moreover, elevated levels of leukocytes, neutrophils, monocytes, LLR, NLR and MLR were associated with treatment resistance. Lastly, higher platelet counts decreased the risk of psychiatric readmissions, while elevated LLR increased this risk. CONCLUSIONS: Elevated levels of WBC counts, ratios, and CRP at the initial diagnosis of SSD are associated with mortality, with CRP demonstrating the highest predictive value. Additionally, certain WBC counts and ratios are associated with treatment resistance and psychiatric readmissions.
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Eating disorders (EDs) commonly co-occur with other psychiatric and neurodevelopmental disorders including attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD); however, the pattern of family history and genetic overlap among them requires clarification. This study investigated the diagnostic, familial, and genetic associations of EDs with ADHD and ASD. The nationwide population-based cohort study included all individuals born in Denmark, 1981-2008, linked to their siblings and cousins. Cox regression was used to estimate associations between EDs and ADHD or ASD, and mediation analysis was used to assess the effects of intermediate mood or anxiety disorders. Polygenic scores (PGSs) were used to investigate the genetic association between anorexia nervosa (AN) and ADHD or ASD. Significantly increased risk for any ED was observed following an ADHD [hazard ratio = 1.97, 95% confidence interval = 1.75-2.22] or ASD diagnosis [2.82, 2.48-3.19]. Mediation analysis suggested that intermediate mood or anxiety disorders could account for 44-100% of the association between ADHD or ASD and ED. Individuals with a full sibling or maternal halfsibling with ASD had increased risk of AN [1.54, 1.33-1.78; 1.45, 1.08-1.94] compared to those with siblings without ASD. A positive association was found between ASD-PGS and AN risk [1.06, 1.02-1.09]. In this study, positive phenotypic associations between EDs and ADHD or ASD, mediation by mood or anxiety disorder, and a genetic association between ASD-PGS and AN were observed. These findings could guide future research in the development of new treatments that can mitigate the development of EDs among individuals with ADHD or ASD.
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BACKGROUND: Psychiatric disorders and type 2 diabetes mellitus (T2DM) are heritable, polygenic, and often comorbid conditions, yet knowledge about their potential shared familial risk is lacking. We used family designs and T2DM polygenic risk score (T2DM-PRS) to investigate the genetic associations between psychiatric disorders and T2DM. METHODS: We linked 659 906 individuals born in Denmark 1990-2000 to their parents, grandparents, and aunts/uncles using population-based registers. We compared rates of T2DM in relatives of children with and without a diagnosis of any or one of 11 specific psychiatric disorders, including neuropsychiatric and neurodevelopmental disorders, using Cox regression. In a genotyped sample (iPSYCH2015) of individuals born 1981-2008 (n = 134 403), we used logistic regression to estimate associations between a T2DM-PRS and these psychiatric disorders. RESULTS: Among 5 235 300 relative pairs, relatives of individuals with a psychiatric disorder had an increased risk for T2DM with stronger associations for closer relatives (parents:hazard ratio = 1.38, 95% confidence interval 1.35-1.42; grandparents: 1.14, 1.13-1.15; and aunts/uncles: 1.19, 1.16-1.22). In the genetic sample, one standard deviation increase in T2DM-PRS was associated with an increased risk for any psychiatric disorder (odds ratio = 1.11, 1.08-1.14). Both familial T2DM and T2DM-PRS were significantly associated with seven of 11 psychiatric disorders, most strongly with attention-deficit/hyperactivity disorder and conduct disorder, and inversely with anorexia nervosa. CONCLUSIONS: Our findings of familial co-aggregation and higher T2DM polygenic liability associated with psychiatric disorders point toward shared familial risk. This suggests that part of the comorbidity is explained by shared familial risks. The underlying mechanisms still remain largely unknown and the contributions of genetics and environment need further investigation.
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Eating disorders are a group of severe and potentially enduring psychiatric disorders associated with increased mortality. Compared to other severe mental illnesses, they have received relatively limited research attention. Epidemiological studies often only report relative measures despite these being difficult to interpret having limited practical use. The aims of this study were to evaluate the incidence and prevalence of diagnosed anorexia nervosa (AN), bulimia nervosa, and eating disorder not otherwise specified recorded in Danish hospital registers and estimate both relative and absolute measures of subsequent mortality - both all-cause and cause-specific in a general nationwide population of 1,667,374 individuals. In a smaller, genetically informed case-cohort sample, the prediction of polygenic scores for AN, body fat percentage, and body mass index on AN prevalence and severity was estimated. Despite males being less likely to be diagnosed with an eating disorder, those that do have significantly increased rates of mortality. AN prevalence was highest for individuals with high AN and low body fat percentage/body mass index polygenic scores.
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Transtornos da Alimentação e da Ingestão de Alimentos , Herança Multifatorial , Sistema de Registros , Humanos , Dinamarca/epidemiologia , Masculino , Feminino , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Transtornos da Alimentação e da Ingestão de Alimentos/mortalidade , Transtornos da Alimentação e da Ingestão de Alimentos/genética , Adulto , Prevalência , Incidência , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Índice de Massa Corporal , Anorexia Nervosa/epidemiologia , Anorexia Nervosa/mortalidade , Anorexia Nervosa/genéticaRESUMO
BACKGROUND: The age of onset (AOO), incidence and cumulative incidence of mental disorders are critical epidemiological measures, providing essential insights into the development and course of these disorders across the lifespan. This study aims to provide up-to-date estimates of the AOO, age-specific incidence, and cumulative incidence for a comprehensive range of mental disorders using data from Danish registers. METHODS: We conducted a follow-up study encompassing all Danish residents from January 1, 2004, to December 31, 2021, totaling 91,613,465 person-years. Data were sourced from the Danish Psychiatric Central Research Register, identifying individuals treated for various mental disorders in psychiatric hospitals, outpatient departments, and accident/emergency departments, that is, treated in secondary care settings. We investigated specific categories of mental disorders, including substance abuse disorders, schizophrenia, mood disorders, anxiety, eating disorders, borderline personality disorders, intellectual disabilities, pervasive developmental disorders, and behavioral and emotional disorders. Age-sex-specific incidence rates were estimated using Poisson generalized linear models, and cumulative incidence was calculated using Aalen-Johansen's competing risks model. The study provides estimates of AOO, incidence, and cumulative incidence for various mental disorders, including their age and sex distributions. RESULTS: The cumulative incidence by age 80 years for any mental disorder was 30.72% (95% confidence interval: 30.62%-30.83%) for males and 34.46% (34.35%-34.57%) for females. The most common types of mental disorders were anxiety-related disorders 16.27% (16.19%-16.36%) for males and 23.39% (23.29%-23.50%) for females, and followed by mood disorder 10.34% (10.27%-10.41%) for males and 16.67% (16.58%-16.77%) for females. For those who develop mental disorder, half will have developed their disorder by approximately age 22 years (median and interquartile range: males 21.37 (11.85-36.00); females 22.55 (16.31-36.08)). CONCLUSIONS: Approximately one in three individuals will seek treatment for at least one mental disorder in a secondary care setting by age 80. Given that half of these individuals develop mental disorders before age 22, it is crucial to tailor service planning to meet the specific needs of young individuals. Web-based interactive data-visualization tools are provided for clinical utility.
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Idade de Início , Transtornos Mentais , Sistema de Registros , Humanos , Dinamarca/epidemiologia , Masculino , Feminino , Sistema de Registros/estatística & dados numéricos , Transtornos Mentais/epidemiologia , Adulto , Incidência , Pessoa de Meia-Idade , Adulto Jovem , Adolescente , Idoso , Criança , Seguimentos , Pré-Escolar , Idoso de 80 Anos ou mais , LactenteRESUMO
OBJECTIVE: Anorexia nervosa (AN) is associated with increased risk of mortality, but little is known about the risk of inpatient admissions and mortality outcomes in individuals with diagnoses of both AN and other psychiatric and somatic conditions. We aimed to investigate the inpatient admissions and mortality among people with AN and other diagnosed conditions using Danish national registers. METHOD: This retrospective cohort study included individuals diagnosed with AN in Denmark, born 1977-2010. We identified other mental and somatic conditions in this population. We used Cox proportional hazards regression to estimate the risk of inpatient admission and mortality, focusing on (i) the number of other diagnosed conditions, and (ii) specific combinations of conditions diagnosed prior to the AN diagnosis. Categories of inpatient admissions considered were due to: (i) AN, (ii) any psychiatric disorder, and (iii) any somatic disorder. Additionally, competing risks survival analysis was used to calculate the cumulative incidence of inpatient admission and all-cause mortality over the follow-up period. RESULTS: The study population included 11,489 individuals. The most common conditions individuals had prior to their AN diagnosis were other eating disorders (34.5%) and anxiety disorders (32.7%). During the follow-up, 3184 (27.7%), 4604 (40.1%), and 6636 (57.8%) individuals were admitted for AN, any psychiatric disorder, and any somatic disorder, respectively; and in total 106 (0.9%) died. The risk of all outcomes was highest among those who had received a higher number of other diagnoses. For most combinations, the risks of admission and mortality were increased. DISCUSSION: Our study presents the prevalence of other conditions in patients with AN in Denmark and elucidates their association with higher rates of inpatient admission and mortality. Our findings highlight the need for comprehensive, multidisciplinary care of patients with AN considering the spectrum of other diagnosed conditions to improve health outcomes.
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Anorexia Nervosa , Transtornos da Alimentação e da Ingestão de Alimentos , Humanos , Anorexia Nervosa/epidemiologia , Pacientes Internados , Estudos Retrospectivos , HospitalizaçãoRESUMO
BACKGROUND: Although several types of risk factors for anorexia nervosa (AN) have been identified, including birth-related factors, somatic, and psychosocial risk factors, their interplay with genetic susceptibility remains unclear. Genetic and epidemiological interplay in AN risk were examined using data from Danish nationwide registers. AN polygenic risk score (PRS) and risk factor associations, confounding from AN PRS and/or parental psychiatric history on the association between the risk factors and AN risk, and interactions between AN PRS and each level of target risk factor on AN risk were estimated. METHODS: Participants were individuals born in Denmark between 1981 and 2008 including nationwide-representative data from the iPSYCH2015, and Danish AN cases from the Anorexia Nervosa Genetics Initiative and Eating Disorder Genetics Initiative cohorts. A total of 7003 individuals with AN and 45 229 individuals without a registered AN diagnosis were included. We included 22 AN risk factors from Danish registers. RESULTS: Risk factors showing association with PRS for AN included urbanicity, parental ages, genitourinary tract infection, and parental socioeconomic factors. Risk factors showed the expected association to AN risk, and this association was only slightly attenuated when adjusted for parental history of psychiatric disorders or/and for the AN PRS. The interaction analyses revealed a differential effect of AN PRS according to the level of the following risk factors: sex, maternal age, genitourinary tract infection, C-section, parental socioeconomic factors and psychiatric history. CONCLUSIONS: Our findings provide evidence for interactions between AN PRS and certain risk-factors, illustrating potential diverse risk pathways to AN diagnosis.
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BACKGROUND: Education is essential for socioeconomic security and long-term mental health; however, mental disorders are often detrimental to the educational trajectory. Genetic correlations between mental disorders and educational attainment do not always align with corresponding phenotypic associations, implying heterogeneity in the genetic overlap. METHODS: We unraveled this heterogeneity by investigating associations between polygenic risk scores for 6 mental disorders and fine-grained school outcomes: school grades in language and mathematics in ninth grade and high school, as well as educational attainment by age 25, using nationwide-representative data from established cohorts (N = 79,489). RESULTS: High polygenic liability of attention-deficit/hyperactivity disorder was associated with lower grades in language and mathematics, whereas high polygenic risk of anorexia nervosa or bipolar disorder was associated with higher grades in language and mathematics. Associations between polygenic risk and school grades were mixed for schizophrenia and major depressive disorder and neutral for autism spectrum disorder. CONCLUSIONS: Polygenic risk scores for mental disorders are differentially associated with language and mathematics school grades.
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Complement components have been linked to schizophrenia and autoimmune disorders. We examined the association between neonatal circulating C3 and C4 protein concentrations in 68,768 neonates and the risk of six mental disorders. We completed genome-wide association studies (GWASs) for C3 and C4 and applied the summary statistics in Mendelian randomization and phenome-wide association studies related to mental and autoimmune disorders. The GWASs for C3 and C4 protein concentrations identified 15 and 36 independent loci, respectively. We found no associations between neonatal C3 and C4 concentrations and mental disorders in the total sample (both sexes combined); however, post-hoc analyses found that a higher C3 concentration was associated with a reduced risk of schizophrenia in females. Mendelian randomization based on C4 summary statistics found an altered risk of five types of autoimmune disorders. Our study adds to our understanding of the associations between C3 and C4 concentrations and subsequent mental and autoimmune disorders.
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INTRODUCTION: Prenatal antidepressant exposure has been associated with lower gestational age and birthweight. Yet, unmeasured residual confounding may inflate this association. We explored if maternal genetic liability for major depression explains part of the association of antidepressant use in pregnancy with lower gestational age and birthweight. MATERIAL AND METHODS: We employed the maternal polygenic score (PGS) for major depression as a measure of genetic liability. We used generalised linear models to estimate the differences in gestational age and birthweight at each PGS quintile between children whose mothers continued antidepressant use during pregnancy (continuation group), children whose mothers discontinued antidepressant use during pregnancy (discontinuation group) and unexposed children. RESULTS: After adjusting for confounders, we found significant differences in birthweight between PGS quintiles in the continuation and unexposed group. Yet, this relationship was not linear. Furthermore, at the lowest and highest PGS quintiles, the continuation group had significantly reduced mean gestational ages (adjusted ß ranges: 1.7-4.5 days, p < 0.001-0.008) and lower mean birthweights (adjusted ß ranges: 58.6-165.4 g, p = 0.001-0.008) than the discontinuation and unexposed groups. CONCLUSION: We confirmed that antidepressant use in pregnancy was associated with small reductions in gestational age and birthweight but found that genetic liability for depression was not linearly associated with this risk. The causality of the observed associations could not be established due to the observational nature of the study. Residual confounding linked to the underlying disease was likely still present.
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BACKGROUND: We quantified relative and absolute risks of postpartum psychiatric episodes (PPE) following risk factors: Young age, past personal or family history of psychiatric disorders, and genetic liability. METHODS: We conducted a register-based study using the iPSYCH2012 case-cohort sample. Exposures were personal history of psychiatric episodes prior to childbirth, being a young mother (giving birth before the age of 21.5 years), having a family history of psychiatric disorders, and a high (highest quartile) polygenic score (PGS) for major depression. PPE was defined within 12 months postpartum by prescription of psychotropic medication or in- and outpatient contact to a psychiatric facility. We included primiparous women born 1981-1999, giving birth before January 1st, 2016. We conducted Cox regression to calculate hazard ratios (HRs) of PPE, absolute risks were calculated using cumulative incidence functions. RESULTS: We included 8174 primiparous women, and the estimated baseline PPE risk was 6.9% (95% CI 6.0%-7.8%, number of PPE cases: 2169). For young mothers with a personal and family history of psychiatric disorders, the absolute risk of PPE was 21.6% (95% CI 15.9%-27.8%). Adding information on high genetic liability to depression, the risk increased to 29.2% (95% CI 21.3%-38.4%) for PPE. CONCLUSIONS: Information on prior personal and family psychiatric episodes as well as age may assist in estimating a personalized risk of PPE. Furthermore, additional information on genetic liability could add even further to this risk assessment.
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The predictive performance of polygenic scores (PGS) is largely dependent on the number of samples available to train the PGS. Increasing the sample size for a specific phenotype is expensive and takes time, but this sample size can be effectively increased by using genetically correlated phenotypes. We propose a framework to generate multi-PGS from thousands of publicly available genome-wide association studies (GWAS) with no need to individually select the most relevant ones. In this study, the multi-PGS framework increases prediction accuracy over single PGS for all included psychiatric disorders and other available outcomes, with prediction R2 increases of up to 9-fold for attention-deficit/hyperactivity disorder compared to a single PGS. We also generate multi-PGS for phenotypes without an existing GWAS and for case-case predictions. We benchmark the multi-PGS framework against other methods and highlight its potential application to new emerging biobanks.
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Transtorno do Deficit de Atenção com Hiperatividade , Estudo de Associação Genômica Ampla , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/genética , Fenótipo , Herança Multifatorial/genéticaRESUMO
The association between antidepressant continuation during pregnancy and postpartum mental health in women with obsessive-compulsive disorder (OCD) is uncertain. We identified 1317 women with live-birth singleton pregnancies and having outpatient/inpatient visits for OCD in the 4 years pre-pregnancy from the Danish registries. We defined three groups based on antidepressant prescriptions filled in the 2 years before pregnancy to delivery: (i) unexposed (n = 449); (ii) discontinuers (n = 346), i.e., with pre-pregnancy antidepressant fills only; (iii) continuers (n = 522), i.e., with antidepressant fills before and during pregnancy. We estimated crude and propensity score weighted hazard ratio (HRs) of postpartum visit for OCD and mood/anxiety disorders using Cox proportional hazard models. In weighted analyses, we found no difference in the probability of a postpartum visit for OCD or MADs with antidepressant continuation compared to unexposed and discontinuers. The likelihood of a postpartum OCD visit was higher in pregnancies having only one prescription fill during pregnancy compared to unexposed (HR = 3.44, 95% CI: 1.24, 9.54) or discontinuers (HR = 2.49, 95% CI: 0.91, 6.83). Continuers in pregnancy without antidepressant fill in the first three months postpartum had higher probability for postpartum visit for mood/anxiety disorders compared to discontinuers (HR = 3.84, 95% CI: 1.49, 9.92). Among pregnant women with pre-existing OCD, we found similar probabilities of a postpartum visit for OCD or mood/anxiety disorders in antidepressant continuers compared to unexposed and discontinuers. Continuers with a single prescription fill during pregnancy or no fill postpartum may have higher risks for these outcomes. Our findings highlight the importance of continuity of treatment throughout the perinatal period.
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Transtorno Obsessivo-Compulsivo , Gestantes , Gravidez , Humanos , Feminino , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Transtorno Obsessivo-Compulsivo/epidemiologia , Transtorno Obsessivo-Compulsivo/psicologia , Antidepressivos/uso terapêutico , Sistema de Registros , Dinamarca/epidemiologiaRESUMO
BACKGROUND: A subgroup of patients with anorexia nervosa (AN) undergoing involuntary treatment (IT) seems to account for most of the IT events. Little is known about these patients and their treatment including the temporal distribution of IT events and factors associated with subsequent utilization of IT. Hence, this study explores (1) utilization patterns of IT events, and (2) factors associated with subsequent utilization of IT in patients with AN. METHODS: In this nationwide Danish register-based retrospective exploratory cohort study patients were identified from their first (index) hospital admission with an AN diagnosis and followed up for 5 years. We explored data on IT events including estimated yearly and total 5-year rates, and factors associated with subsequent increased IT rates and restraint, using regression analyses and descriptive statistics. RESULTS: IT utilization peaked in the initial few years starting at or following the index admission. A small percentage (1.0%) of patients accounted for 67% of all IT events. The most frequent measures reported were mechanical and physical restraint. Factors associated with subsequent increased IT utilization were female sex, lower age, previous admissions with psychiatric disorders before index admission, and IT related to those admissions. Factors associated with subsequent restraint were lower age, previous admissions with psychiatric disorders, and IT related to these. CONCLUSIONS: High IT utilization in a small percentage of individuals with AN is concerning and can lead to adverse treatment experiences. Exploring alternative approaches to treatment that reduce the need for IT is an important focus for future research.
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Anorexia Nervosa , Tratamento Involuntário , Humanos , Feminino , Masculino , Anorexia Nervosa/terapia , Estudos de Coortes , Estudos Retrospectivos , HospitalizaçãoRESUMO
OBJECTIVE: To examine sex differences in risk factors for anorexia nervosa (AN). METHOD: This population-based study involved 44,743 individuals (6,239 AN cases including 5,818 females and 421 males, and 38,504 controls including 18,818 females and 19,686 males) born in Denmark between May 1981 and December 2009. Follow-up began on the individual's sixth birthday and ended at AN diagnosis, emigration, death, or December 31, 2016, whichever occurred first. Exposures included socioeconomic status (SES), pregnancy, birth, and early childhood factors based on data from Danish registers, and psychiatric and metabolic polygenic risk scores (PRS) based on genetic data. Hazard ratios were estimated using weighted Cox proportional hazards models stratified by sex (assigned at birth), with AN diagnosis as the outcome. RESULTS: The effects of early life exposures and PRS on AN risk were comparable between females and males. Although we observed some differences in the magnitude and direction of effects, there were no significant interactions between sex and SES, pregnancy, birth, or early childhood exposures. The effects of most PRS on AN risk were highly similar between the sexes. We observed significant sex-specific effects of parental psychiatric history and body mass index PRS, though these effects did not survive corrections for multiple comparisons. CONCLUSIONS: Risk factors for AN are comparable between females and males. Collaboration across countries with large registers is needed to further investigate sex-specific effects of genetic, biological, and environmental exposures on AN risk, including exposures in later childhood and adolescence as well as the additive effects of exposures. PUBLIC SIGNIFICANCE: Sex differences in the prevalence and clinical presentation of AN warrant examination of sex-specific risk factors. This population-based study indicates that the effects of polygenic risk and early life exposures on AN risk are comparable between females and males. Collaboration between countries with large registers is needed to further investigate sex-specific AN risk factors and improve early identification of AN.
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Anorexia Nervosa , Gravidez , Recém-Nascido , Adolescente , Humanos , Masculino , Feminino , Pré-Escolar , Anorexia Nervosa/epidemiologia , Anorexia Nervosa/genética , Anorexia Nervosa/diagnóstico , Caracteres Sexuais , Fatores de Risco , Pais , Medição de RiscoRESUMO
OBJECTIVE: Anxiety and depression symptoms are common in individuals with eating disorders. To study these co-occurrences, we need high-quality self-report questionnaires. The 19-item self-rated Comprehensive Psychopathological Rating Scale for Affective Syndromes (CPRS-S-A) is not validated in patients with eating disorders. We tested its factor structure, invariance, and differences in its latent dimensions. METHOD: Patients were registered by 45 treatment units in the Swedish nationwide Stepwise quality assurance database for specialised eating disorder care (n = 9509). Patients self-reported their anxiety and depression symptoms on the CPRS-S-A. Analyses included exploratory and confirmatory factor analyses (CFA) in split samples, and testing of invariance and differences in subscales across eating disorder types. RESULTS: Results suggested a four-factor solution: Depression, Somatic and fear symptoms, Disinterest, and Worry. Multigroup CFA indicated an invariant factor structure. We detected the following differences: Patients with anorexia nervosa binge-eating/purging subtype scored the highest and patients with unspecified feeding and eating disorders the lowest on all subscales. Patients with anorexia nervosa or purging disorder show more somatic and fear symptoms than individuals with either bulimia nervosa or binge-eating disorder. CONCLUSION: Our four-factor solution of the CPRS-S-A is suitable for patients with eating disorders and may help to identify differences in anxiety and depression dimensions amongst patients with eating disorders.
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Anorexia Nervosa , Transtorno da Compulsão Alimentar , Transtornos da Alimentação e da Ingestão de Alimentos , Humanos , Depressão/epidemiologia , Depressão/psicologia , Suécia/epidemiologia , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Transtorno da Compulsão Alimentar/diagnóstico , Transtorno da Compulsão Alimentar/psicologia , Anorexia Nervosa/epidemiologia , Anorexia Nervosa/diagnóstico , Ansiedade/epidemiologiaRESUMO
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. Mendelian randomization analyses identify a unidirectional effect of higher DBP concentration and (a) higher 25-hydroxyvitamin D concentration, and (b) a reduced risk of multiple sclerosis and rheumatoid arthritis. A phenome-wide association study confirms that higher DBP concentration is associated with a reduced risk of vitamin D deficiency. Our findings provide valuable insights into the influence of DBP on vitamin D status and a range of health outcomes.
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Estudo de Associação Genômica Ampla , Proteína de Ligação a Vitamina D , Recém-Nascido , Humanos , Proteína de Ligação a Vitamina D/genética , Vitamina D/genética , Calcifediol , Vitaminas , Polimorfismo de Nucleotídeo Único , Proteínas Citotóxicas Formadoras de Poros/genéticaRESUMO
OBJECTIVE: Increasing rates of caesarean sections has led to concerns about long-term effects on the offspring's health, and it has been hypothesised that caesarean section induced differences in the child's microbiota could potentially increase the risk of mental disorders. METHODS: Nationwide Danish cohort study of 2,196,687 births was conducted between 1980 and 2015, with 38.5 million observation-years. Exposure was 'Caesarean Section' and outcome was the child's risk of any mental disorder. Absolute and relative risks (RRs) were estimated using inverse probability weighting to adjust for age, calendar time and confounding variables while accounting for the competing risk of death. RESULTS: Caesarean section (n = 364,908, 16.6%), compared to vaginal birth, was associated with a small RR increase of 8% (RR, 1.08; 95% CI, 1.04-1.13; n = 44,352) for the development of any in-patient psychiatric admission at age 36 for the offspring and with a small absolute risk difference of 0.47% (95% CI, 0.23-0.76). When looking at all in-patient, out-patient and emergency room psychiatric contacts among people born after 1995, the effect was diminished (RR, 1.04; 95% CI, 0.99-1.09; n = 15,211). The risk was comparable when comparing prelabour versus intrapartum caesarean section (RR, 0.98; 95% CI, 0.90-1.08) and acute versus planned caesarean section (RR, 1.00; 95% CI, 0.80-1.29). CONCLUSION: Birth by caesarean section was associated with only a very slightly increased risk of any in-patient psychiatric admission for the offspring and diminished even further when including all psychiatric contacts. The very small associations observed may be explained by unmeasured confounding and is unlikely to be of substantial clinical relevance.