scholarly journals Genetic factors underlying the bidirectional relationship between autoimmune and mental disorders – findings from a Danish population-based study

2019 ◽  
Author(s):  
Xueping Liu ◽  
Ron Nudel ◽  
Wesley K. Thompson ◽  
Vivek Appadurai ◽  
Andrew J. Schork ◽  
...  

AbstractBackgroundPrevious studies have indicated the bidirectionality between autoimmune and mental disorders. However, genetic studies underpinning the co-occurrence of the two disorders have been lacking. In this study, we examined the potential genetic contribution to the association between autoimmune and mental disorders.MethodsWe used diagnostic information for patients with seven autoimmune diseases and six mental disorders from the Danish population-based case-cohort sample (iPSYCH2012). We explored the epidemiological association using survival analysis and modelled the effect of polygenic risk scores (PRSs) on two diseases. The genetic factors were investigated using GWAS and HLA imputation data based on iPSYCH cohort.ResultsAmong 64,039 individuals, a total of 43,902 (68.6%) were diagnosed with mental disorders and 1,383 (2.2%) with autoimmune diseases. There was a significant comorbidity between the two diseases (P=2.67×10-7, OR=1.38, 95%CI=1.22-1.56), with an overall bidirectional association wherein individuals with autoimmune diseases had an increased risk of subsequent mental disorders (HR=1.13, 95%CI: 1.07-1.21, P=7.95×10-5) and vice versa (HR=1.27, 95%CI=1.16-1.39, P=8.77×10-15). Though PRSs were significantly correlated with both types of diagnosis, PRSs had little effect on the bidirectional relationship. Importantly, we for the first time observed 12 human leukocyte antigen (HLA) loci and 20 HLA alleles strongly associated with overall autoimmune diseases, but we did not find significant evidence of their associations with overall mental disorders.ConclusionsOur findings confirm the overall comorbidity and bidirectionality between autoimmune and mental disorders and discover HLA genes which are significantly associated with overall autoimmune diseases, but not with overall mental disorders.

Author(s):  
Jessica Samuelsson ◽  
Jenna Najar ◽  
Ola Wallengren ◽  
Silke Kern ◽  
Hanna Wetterberg ◽  
...  

Abstract Purpose To investigate potential interactions between dietary patterns and genetic factors modulating risk for Alzheimer’s disease (AD) in relation to incident dementia. Methods Data were derived from the population-based Gothenburg H70 Birth Cohort Studies in Sweden, including 602 dementia-free 70-year-olds (examined 1992–93, or 2000–02; 64% women) followed for incident dementia until 2016. Two factors from a reduced rank regression analysis were translated into dietary patterns, one healthy (e.g., vegetables, fruit, and fish) and one western (e.g., red meat, refined cereals, and full-fat dairy products). Genetic risk was determined by APOE ε4 status and non-APOE AD-polygenic risk scores (AD-PRSs). Gene–diet interactions in relation to incident dementia were analysed with Cox regression models. The interaction p value threshold was < 0.1. Results There were interactions between the dietary patterns and APOE ε4 status in relation to incident dementia (interaction p value threshold of < 0.1), while no evidence of interactions were found between the dietary patterns and the AD-PRSs. Those with higher adherence to a healthy dietary pattern had a reduced risk of dementia among ε4 non-carriers (HR: 0.77; 95% CI: 0.61; 0.98), but not among ε4 carriers (HR: 0.86; CI: 0.63; 1.18). Those with a higher adherence to the western dietary pattern had an increased risk of dementia among ε4 carriers (HR: 1.37; 95% CI: 1.05; 1.78), while no association was observed among ε4 non-carriers (HR: 0.99; CI: 0.81; 1.21). Conclusions The results of this study suggest that there is an interplay between dietary patterns and APOE ε4 status in relation to incident dementia.


Author(s):  
Khalaf Kridin ◽  
Jennifer E. Hundt ◽  
Ralf J. Ludwig ◽  
Kyle T. Amber ◽  
Dana Tzur Bitan ◽  
...  

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.


2012 ◽  
Vol 200 (5) ◽  
pp. 374-380 ◽  
Author(s):  
Shaw-Ji Chen ◽  
Yu-Lin Chao ◽  
Chuan-Yu Chen ◽  
Chia-Ming Chang ◽  
Erin Chia-Hsuan Wu ◽  
...  

BackgroundThe association between autoimmune diseases and schizophrenia has rarely been systematically investigated.AimsTo investigate the association between schizophrenia and a variety of autoimmune diseases and to explore possible gender variation in any such association.MethodTaiwan's National Health Insurance Research Database was used to identify 10 811 hospital in-patients with schizophrenia and 108 110 age-matched controls. Univariate and multiple logistic regression analyses were performed, separately, to evaluate the association between autoimmune diseases and schizophrenia. We applied the false discovery rate to correct for multiple testing.ResultsWhen compared with the control group, the in-patients with schizophrenia had an increased risk of Graves' disease (odds ratio (OR) = 1.32, 95% CI 1.04–1.67), psoriasis (OR = 1.48, 95% CI 1.07–2.04), pernicious anaemia (OR = 1.71, 95% CI 1.04–2.80), celiac disease (OR = 2.43, 95% CI 1.12–5.27) and hypersensitivity vasculitis (OR = 5.00, 95% CI 1.64–15.26), whereas a reverse association with rheumatoid arthritis (OR = 0.52, 95% CI 0.35–0.76) was also observed. Gender-specific variation was found for Sjögren syndrome, hereditary haemolytic anaemia, myasthenia gravis, polymyalgia rheumatica and dermatomyositis.ConclusionsSchizophrenia was associated with a greater variety of autoimmune diseases than was anticipated. Further investigation is needed to gain a better understanding of the aetiology of schizophrenia and autoimmune diseases.


2019 ◽  
Vol 8 (1) ◽  
pp. 115 ◽  
Author(s):  
Yu-Huei Huang ◽  
Chang-Fu Kuo ◽  
Lu-Hsiang Huang ◽  
Mei-Yun Hsieh

Psoriasis is considered to result from the interaction of genetic factors and environmental exposure. The evidence for familial aggregation in psoriasis has been reported but population-based studies related to the magnitude of genetic contribution to psoriasis are rare. This study aimed to evaluate the relative risks of psoriasis in individuals with affected relatives and to calculate the proportion of genetic, shared, and non-shared environmental factors contributing to psoriasis. The study cohort included 69,828 patients diagnosed with psoriasis enrolled in National health Insurance in 2010. The adjusted relative risks (RR) for individuals with an affected first-degree relative and affected second-degree relative were 5.50 (95% CI (Confidence Interval), 5.19–5.82) and 2.54 (95% CI, 2.08–3.12) respectively. For those who have affected first-degree relatives, their RR was 1.45 (95% CI, 1.17–1.79) for Sjogren’s syndrome and 1.94 (95% CI, 1.15–3.27) for systemic sclerosis. This nationwide study ascertains that family history of psoriasis is a risk factor for psoriasis. Individuals with relatives affected by psoriasis have higher risks of developing some autoimmune diseases.


Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2580
Author(s):  
Yu-Jin Kwon ◽  
Jung Oh Kim ◽  
Jae-Min Park ◽  
Ja-Eun Choi ◽  
Da-Hyun Park ◽  
...  

The role of sodium in hypertension remains unresolved. Although genetic factors have a significant impact on high blood pressure, studies comparing genetic susceptibility between people with low and high sodium diets are lacking. We aimed to investigate the genetic variations related to hypertension according to sodium intake habits in a large Korean population-based study. Data for a total of 57,363 participants in the Korean Genome and Epidemiology Study Health Examination were analyzed. Sodium intake was measured by a semi-quantitative food frequency questionnaire. We classified participants according to sodium intake being less than or greater than 2 g/day. We used logistic regression to test single-marker variants for genetic association with a diagnosis of hypertension, adjusting for age, sex, body mass index, exercise, alcohol, smoking, potassium intake, principal components 1, and principal components 2. Significant associations were defined as p < 5 × 10−8. In participants whose sodium intake was greater than 2 g/day, chromosome 6 open reading frame 10 (C6orf10)-human leukocyte antigen (HLA)-DQB1 rs6913309, ring finger protein (RNF)213 rs112735431, glycosylphosphatidylinositol anchored molecule-like (GML)- cytochrome P450 family 11 subfamily B member 1(CYP11B1) rs3819496, myosin light chain 2 (MYL2)-cut like homeobox 2 (CUX2) rs12229654, and jagged1 (JAG1) rs1887320 were significantly associated with hypertension. In participants whose intake was less than 2 g/day, echinoderm microtubule-associated protein-like 6(EML6) rs67617923 was significantly associated with hypertension. Genetic susceptibility associated with hypertension differed according to sodium intake. Identifying gene variants that contribute to the dependence of hypertension on sodium intake status could make possible more individualized nutritional recommendations for preventing cardiovascular diseases.


2012 ◽  
Vol 38 (2-3) ◽  
pp. J120-J128 ◽  
Author(s):  
Kristian Tore Jørgensen ◽  
Nete Munk Nielsen ◽  
Bo Vestergaard Pedersen ◽  
Søren Jacobsen ◽  
Morten Frisch

2007 ◽  
Vol 22 (3) ◽  
pp. 142-145 ◽  
Author(s):  
Christine Kuehner ◽  
Peter Gass ◽  
Harald Dressing

AbstractPurposePopulation-based studies on the relationship between stalking and mental health outcomes in victims are scarce. The aim of the present study was to assess associations between stalking victimization and specific DSM-IV mental disorders in a community sample.MethodA postal survey was conducted in a middle-sized German city (sample size = 675). Lifetime stalking victims and non-victims were compared regarding rates of any mental disorder, comorbid mental disorders, and specific disorders assessed by the Patient Health Questionnaire (PHQ).ResultsVictims had a higher incidence of mental disorders and comorbid mental disorders. Sex- and age-adjusted rates of specific disorders were increased, with the most robust associations identified for major depression (OR 4.8, 95% CI 1.8–12.8) and panic disorder (OR 4.1, 95% CI 1.1–14.9). Victims also reported higher current use of psychotropic medication (20.8% versus 5.6%).ConclusionsOur study indicates substantial associations between stalking victimization and impaired mental health that can be quantified at diagnostic levels in the general population. To confirm these findings, larger community studies are needed, which also include an assessment of lifetime psychopathology and of factors potentially mediating the associations between stalking victimization and mental health.


2017 ◽  
Vol 48 (3) ◽  
pp. 416-425 ◽  
Author(s):  
J. Nyberg ◽  
M. Henriksson ◽  
M. A. I. Åberg ◽  
A. Rosengren ◽  
M. Söderberg ◽  
...  

BackgroundCardiovascular fitness in late adolescence is associated with future risk of depression. Relationships with other mental disorders need elucidation. This study investigated whether fitness in late adolescence is associated with future risk of serious non-affective mental disorders. Further, we examined how having an affected brother might impact the relationship.MethodProspective, population-based cohort study of 1 109 786 Swedish male conscripts with no history of mental illness, who underwent conscription examinations at age 18 between 1968 and 2005. Cardiovascular fitness was objectively measured at conscription using a bicycle ergometer test. During the follow-up (3–42 years), incident cases of serious non-affective mental disorders (schizophrenia and schizophrenia-like disorders, other psychotic disorders and neurotic, stress-related and somatoform disorders) were identified through the Swedish National Hospital Discharge Register. Cox proportional hazards models were used to assess the influence of cardiovascular fitness at conscription and risk of serious non-affective mental disorders later in life.ResultsLow fitness was associated with increased risk for schizophrenia and schizophrenia-like disorders [hazard ratio (HR) 1.44, 95% confidence interval (CI) 1.29–1.61], other psychotic disorders (HR 1.41, 95% CI 1.27–1.56), and neurotic or stress-related and somatoform disorders (HR 1.45, 95% CI 1.37–1.54). Relationships persisted in models that included illness in brothers.ConclusionsLower fitness in late adolescent males is associated with increased risk of serious non-affective mental disorders in adulthood.


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