Social trust is a heritable trait that has been linked with physical health and longevity. In this study, we performed genome-wide association studies of self-reported social trust in n = 33,882 ...Danish blood donors. We observed genome-wide and local evidence of genetic similarity with other brain-related phenotypes and estimated the single nucleotide polymorphism-based heritability of trust to be 6% (95% confidence interval = (2.1, 9.9)). In our discovery cohort (n = 25,819), we identified one significantly associated locus (lead variant: rs12776883) in an intronic enhancer region of PLPP4, a gene highly expressed in brain, kidneys, and testes. However, we could not replicate the signal in an independent set of donors who were phenotyped a year later (n = 8063). In the subsequent meta-analysis, we found a second significantly associated variant (rs71543507) in an intergenic enhancer region. Overall, our work confirms that social trust is heritable, and provides an initial look into the genetic factors that influence it.
Transfusion‐Related Acute Lung Injury (TRALI) has been associated with neutrophil reacting antibodies in transfused blood products. We report a case of life‐threatening TRALI in an obstetric patient ...triggered by transfusion from a non‐transfused male blood donor. A residual risk of TRALI exist, even in a male‐only plasma setting.
Transfusion‐Related Acute Lung Injury (TRALI) has been associated with neutrophil reacting antibodies in transfused blood products. We report a case of life‐threatening TRALI in an obstetric patient triggered by transfusion from a non‐transfused male blood donor. A residual risk of TRALI exist, even in a male‐only plasma setting.
Autoimmune neutropenia (AIN) of early childhood is caused by autoantibodies against antigens on the neutrophil membrane. Human leukocyte antigens (HLA) have previously been associated with AIN. This ...study investigated HLA-DRB1 and HLA-DQB1 alleles in 160 antibody positive patients and compared with 1000 controls. Increased risk was observed for DRB1*10, DRB1*14, DRB1*16 and DQB1*05, and lower risk for DRB1*04, DRB1*13 and DQB1*03. Haplotypes with higher risk included: DRB1*10/DQB1*05, DRB1*14/DQB1*05 and DRB1*16/DQB1*05, while DRB1*04/DQB1*03, DRB1*07/DQB1*02, and DRB1*13/DQB1*06 were associated with lower risk. Associated HLA-DRB1 and –DQB1 differed between patients positive for anti-HNA-1a-specific antibodies and patients positive for broad reactive anti-FcγRIIIb antibodies. DRB1*01, DRB1*04 and DQB1*03 was only associated for anti-HNA-1a positive, and DRB1*10 was restricted to broad reactive anti-FcγRIIIb positive. Strong association between AIN and HLA-DRB1 and -DQB1 alleles and haplotypes suggested that they play a role in susceptibility or protection. Different associations regarding FcγRIIIb antibody specificities could indicate disease heterogeneity.
This case suggests a mechanistic rationale for the clinical efficacy of intravenous immunoglobulins (IVIG) in treating CD40 ligand (CD40L) deficiency associated neutropenia as it is the first ...reported instance of free and cell‐bound antineutrophil antibodies in a case of CD40L deficiency, accompanied by a prolonged and clinically severe neutropenia.
This case suggests a mechanistic rationale for the clinical efficacy of intravenous immunoglobulins (IVIG) in treating CD40 ligand (CD40L) deficiency associated neutropenia as it is the first reported instance of free and cell‐bound antineutrophil antibodies in a case of CD40L deficiency, accompanied by a prolonged and clinically severe neutropenia.
•HSV-1 infection could be a contributing factor for suicidal behavior.•HSV-1 infection could be a causal contributing factor for psychiatric disorders.•HSV-1 infection occurred prior first registered ...psychiatric diagnosis.
Increasing evidence shows that latent infections and inflammation is associated with cognitive and behavioral changes in humans. This case-control study investigates the association between Herpes Simplex Virus Type 1 (HSV-1) infection and C-reactive Protein (CRP) levels, and psychiatric disorders and suicidal behavior. Public health register data from 81,912 participants in the Danish Blood Donor Study, were reviewed to identify individuals registered with an ICD-10 code of any psychiatric diagnosis, or who had attempted or committed suicide. We found 1,504 psychiatric cases and 353 suicidal cases; for all cases, controls were frequency-matched by age and sex, resulting in 5,336 participants. Plasma samples were analyzed for IgG-class antibodies against HSV-1 and CRP. HSV-1 infection was associated with suicidal behavior (odds-ratio, 1.40; 95% confidence interval CI 1.11–1.77). Accounting for temporality, HSV-1 infection was associated with having first psychiatric disorder after the date of blood collection (incidence rate ration, 1.44; 95% CI, 1.05–1.95). No association between CRP and psychiatric disorders or suicidal behavior was found. The finding that HSV-1 was associated with suicidal behavior and first psychiatric disorder indicates that infection may play a role in the etiology and pathogenesis of suicidal behavior and development of psychiatric disorders.
The clinical presentation of CD21 deficiency in 2 siblings caused by a novel mutation in the CD21 gene is reported, and the frequency of this mutation in the Danish population is explored. Successful ...treatment with IgG replacement in both patients with CD21 deficiency is also reported.
Blood transfusion is an essential component of a modern healthcare system. Because knowledge about blood donor demography may inform the design of strategies for donor recruitment and retention, we ...used nationwide registers to characterize the entire population of blood donors in Denmark in 2010.
The study population comprised all Danes in the age range eligible for blood donation (N = 3,236,753) at the end of 2010. From the Scandinavian Donations and Transfusions (SCANDAT) register, we identified 174,523 persons who donated blood in Danish blood banks at least once in 2010. The association between sociodemographic characteristics and blood donor prevalence was examined using regression models.
The overall prevalence of blood donation was 5.4% among both women and men. The age-specific prevalence of blood donation peaked at 25 years of age (6.8%) for women and 30 years of age (5.7%) for men. Children of any age were associated with lower prevalence of blood donation among women, while the opposite was seen for men. Middle to high income groups, but not the highest income group, had fourfold higher donor prevalence than the lowest income group (6.7% compared to 1.7%). The prevalence of blood donation was considerably lower among men living with their parents (2.9%) or alone (3.9%) than among men cohabitating with a woman (6.2%).
Social marginalization, as indicated by low income and being a male living without a woman, was associated with lower prevalence of blood donation. However, individuals with very high incomes and women with children were underrepresented in the Danish blood donor population.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•T. gondii infection might be a contributing causal factor for schizophrenia.•CMV infection might be a contributing causal factor for any psychiatric disorder.•CMV infection was associated with ...attempting or committing suicide.
Common infectious pathogens have been associated with psychiatric disorders, self-violence and risk-taking behavior.
This case-control study reviews register data on 81,912 individuals from the Danish Blood Donor Study to identify individuals who have a psychiatric diagnosis (N = 2591), have attempted or committed suicide (N = 655), or have had traffic accidents (N = 2724). For all cases, controls were frequency matched by age and sex, resulting in 11,546 participants.
Plasma samples were analyzed for immunoglobulin G (IgG) antibodies against Toxoplasma gondii and cytomegalovirus (CMV).
T. gondii was detected in 25·9% of the population and was associated with schizophrenia (odds ratio OR, 1·47; 95% confidence interval CI, 1·03–2·09). Accounting for temporality, with pathogen exposure preceding outcome, the association was even stronger (IRR, 2·78; 95% CI, 1·27–6·09). A very weak association between traffic accident and toxoplasmosis (OR, 1·11; 95% CI, 1·00–1·23, p = 0.054) was found.
CMV was detected in 60·8% of the studied population and was associated with any psychiatric disorder (OR, 1·17; 95% CI, 1·06–1·29), but also with a smaller group of neurotic, stress-related, and somatoform disorders (OR, 1·27; 95% CI, 1·12–1·44), and with attempting or committing suicide (OR, 1·31; 95% CI, 1·10–1·56). Accounting for temporality, any psychiatric disorder (IRR, 1·37; 95% CI, 1·08–1·74) and mood disorders (IRR, 1·43; 95% CI, 1·01–2·04) were associated with exposure to CMV. No association between traffic accident and CMV (OR, 1·06; 95% CI, 0·97–1·17) was found.
This large-scale serological study is the first study to examine temporality of pathogen exposure and to provide evidence of a causal relationship between T. gondii and schizophrenia, and between CMV and any psychiatric disorder.
The emerging use of biomarkers in research and tailored care introduces a need for information about the association between biomarkers and basic demographics and lifestyle factors revealing ...expectable concentrations in healthy individuals while considering general demographic differences.
A selection of 47 biomarkers, including markers of inflammation and vascular stress, were measured in plasma samples from 9876 Danish Blood Donor Study participants. Using regression models, we examined the association between biomarkers and sex, age, Body Mass Index (BMI), and smoking.
Here we show that concentrations of inflammation and vascular stress biomarkers generally increase with higher age, BMI, and smoking. Sex-specific effects are observed for multiple biomarkers.
This study provides comprehensive information on concentrations of 47 plasma biomarkers in healthy individuals. The study emphasizes that knowledge about biomarker concentrations in healthy individuals is critical for improved understanding of disease pathology and for tailored care and decision support tools.
Osteoarthritis is a common and severe, multifactorial disease with a well-established genetic component. However, little is known about how genetics affect disease progression, and thereby the need ...for joint placement. Therefore, we aimed to investigate whether the genetic associations of knee and hip osteoarthritis differ between patients treated with joint replacement and patients without joint replacement.
We included knee and hip osteoarthritis cases along with healthy controls, altogether counting >700 000 individuals. The cases were divided into two groups based on joint replacement status (surgical vs non-surgical) and included in four genome-wide association meta-analyses: surgical knee osteoarthritis (N = 22 525), non-surgical knee osteoarthritis (N = 38 626), surgical hip osteoarthritis (N = 20 221) and non-surgical hip osteoarthritis (N = 17 847). In addition, we tested for genetic correlation between the osteoarthritis groups and the pain phenotypes intervertebral disc disorder, dorsalgia, fibromyalgia, migraine and joint pain.
We identified 52 sequence variants associated with knee osteoarthritis (surgical: 17, non-surgical: 3) or hip osteoarthritis (surgical: 34, non-surgical: 1). For the surgical phenotypes, we identified 10 novel variants, including genes involved in autophagy (rs2447606 in
) and mechanotransduction (rs202127176 in
). One variant, rs13107325 in
, associated more strongly with non-surgical knee osteoarthritis than surgical knee osteoarthritis. For all other variants, significance and effect sizes were higher for the surgical phenotypes. In contrast, genetic correlations with pain phenotypes tended to be stronger in the non-surgical groups.
Our results indicate differences in genetic associations between knee and hip osteoarthritis depending on joint replacement status.
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