| 1. |
- Hess, Timo, et al.
(författare)
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Dissecting the genetic heterogeneity of gastric cancer
- 2023
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 92
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture.Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO.Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level.Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO.
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| 2. |
- Angst, Jules, et al.
(författare)
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The HCL-32 : towards a self-assessment tool for hypomanic symptoms in outpatients
- 2005
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Ingår i: Journal of Affective Disorders. - Amsterdam : Elsevier. - 0165-0327 .- 1573-2517. ; 88:2, s. 217-233
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Tidskriftsartikel (refereegranskat)abstract
- Background: Bipolar disorders (BP) are frequently diagnosed and treated as pure depression initially; accurate diagnosis often being delayed by 8 to 10 years. In prospective studies, the presence of hypomanic symptoms in adolescence is strongly predictive of later bipolar disorders. As such, an instrument for self-assessment of hypomanic symptoms might increase the detection of suspected and of manifest, but under-treated, cases of bipolar disorders.Methods: The multi-lingual hypomania checklist (HCL-32) has been developed and is being tested internationally. This preliminary paper reports the performance of the scale in distinguishing individuals with BP (N=266) from those with major depressive disorder (MDD; N= 160). The samples were adult psychiatry patients recruited in Italy (N= 186) and Sweden (N=240).Results: The samples reported similar clinical profiles and the structure for the HCL-32 demonstrated two main factors identified as "active/elated" hypomania and "risk-taking/irritable" hypomania. The HCL-32 distinguished between BP and MDD with a sensitivity of 80% and a specificity of 51%.Limitations: Although the HCL-32 is a sensitive instrument for hypomanic symptoms, it does not distinguish between BP-1 and BP-11 disorders.Conclusions: Future studies should test if different combinations of items. possibly recording the consequences of hypomania, can distinguish between these BP subtypes.
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| 3. |
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| 4. |
- Hemmingsson, Eva-Stina, et al.
(författare)
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Antiviral treatment associated with reduced risk of clinical Alzheimer's disease : A nested case-control study
- 2021
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Ingår i: Alzheimer’s & Dementia. - : John Wiley & Sons. - 2352-8737. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: In this nested case-control study, we investigated if antiviral treatment given prior to onset of Alzheimer's disease (AD) could influence incident AD.Methods: From a large population-based cohort study in northern Sweden, 262 individuals that later developed AD were compared to a non-AD matched control group with respect to prescriptions of herpes antiviral treatment. All included subjects were herpes simplex virus 1 (HSV1) carriers and the matching criteria were age, sex, apolipoprotein E genotype (ε4 allele carriership), and study sample start year.Results: Among those who developed AD, 6 prescriptions of antivirals were found, compared to 20 among matched controls. Adjusted for length of follow-up, a conditional logistic regression indicated a difference in the risk for AD development between groups (odds ratio for AD with an antiviral prescription 0.287, P = .018).Discussion: Antiviral treatment might possibly reduce the risk for later development of HSV1-associated AD.
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| 5. |
- Lövheim, Hugo, 1981-, et al.
(författare)
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Herpes Simplex Virus, APOE ɛ4, and Cognitive Decline in Old Age : Results from the Betula Cohort Study
- 2019
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Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 67:1, s. 211-220
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Tidskriftsartikel (refereegranskat)abstract
- Background: Herpes simplex virus (HSV) has been suggested to play a role in Alzheimer’s disease (AD) development.Objective: The aim of the present study was to investigate the early AD-related symptom episodic memory decline in relation to HSV and carriage of allele 4 of the apolipoprotein E gene (APOE ɛ4) in a large population-based cohort with a long follow-up time.Methods: The study included 3,413 persons, with longitudinal data available for 1,293 persons with a mean follow-up time of 11.6 years. The associations between HSV carriage, APOE ɛ4 carriage, and episodic memory was investigated at baseline, as well as in longitudinal analyses where individuals with and without HSV antibodies (HSV1/2 non-specific) were matched and episodic memory decline compared.Results: Cross-sectional analyses revealed an age-dependent association of HSV carriage with lower episodic memory function, particularly among APOE ɛ4 carriers (p = 0.008). Longitudinal analyses showed an increased risk of episodic memory decline in HSV carriers (≥65 years: p < 0.001, all ages: non-significant), and a significant interaction between HSV and APOE ɛ4 for episodic memory decline (p < 0.001).Conclusion: In this large population-based cohort study, both cross-sectional and longitudinal results support an association between HSV carriage and declining episodic memory function, especially among APOE ɛ4 carriers. The results strengthen the hypothesis that HSV is associated with AD development.
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| 6. |
- Mousavi, Malahat, et al.
(författare)
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Serum metabolomic biomarkers of dementia
- 2014
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Ingår i: Dementia and Geriatric Cognitive Disorders Extra. - : S. Karger AG. - 1664-5464. ; 4:2, s. 252-62
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Tidskriftsartikel (refereegranskat)abstract
- Aims: This study compared serum metabolites of demented patients (Alzheimer's disease and vascular dementia) and controls, and explored serum metabolite profiles of nondemented individuals 5 years preceding the diagnosis. Methods: Cognitively healthy participants were followed up for 5-20 years. Cognitive assessment, serum sampling, and diagnosis were completed every 5 years. Multivariate analyses were conducted on the metabolite profiles generated by gas chromatography/time-of-flight mass spectrometry. Results: A significant group separation was found between demented patients and controls, and between incident cases and controls. Metabolites that contributed in both analyses were 3,4-dihydroxybutanoic acid, docosapentaenoic acid, and uric acid. Conclusions: Serum metabolite profiles are altered in demented patients, and detectable up to 5 years preceding the diagnosis. Blood sampling can make an important contribution to the early prediction of conversion to dementia.
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| 7. |
- Olsson, Jan, et al.
(författare)
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Herpes virus seroepidemiology in the adult Swedish population
- 2017
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Ingår i: Immunity & Ageing. - : BioMed Central (BMC). - 1742-4933. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Herpes viruses establish a life-long latency and can cause symptoms during both first-time infection and later reactivation. The aim of the present study was to describe the seroepidemiology of Herpes simplex type 1 (HSV1), Herpes simplex type 2 (HSV2), Cytomegalovirus (CMV), Varicella Zoster virus (VZV) and Human herpes virus type 6 (HHV6) in an adult Swedish population (35-95 years of age). Methods: Presence of antibodies against the respective viruses in serum from individuals in the Betula study was determined with an enzyme-linked immunosorbent assay (ELISA). Singular samples from 535 persons (53.9% women, mean age at inclusion 62.7 +/- 14.4 years) collected 2003-2005 were analyzed for the five HHVs mentioned above. In addition, samples including follow-up samples collected 1988-2010 from 3,444 persons were analyzed for HSV. Results: Prevalence of HSV1 was 79.4%, HSV2 12.9%, CMV 83.2%, VZV 97.9%, and HHV6 97.5%. Herpes virus infections were more common among women (p = 0.010) and a lower age-adjusted HSV seroprevalence was found in later birth cohorts (p < 0.001). The yearly incidence of HSV infection was estimated at 14.0/1000. Conclusion: Women are more often seropositive for HHV, especially HSV2. Age-adjusted seroprevalence for HSV was lower in later birth cohorts indicating a decreasing childhood and adolescent risk of infection.
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| 8. |
- Van Schijndel, Jessica E., et al.
(författare)
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Dual association of a TRKA polymorphism with schizophrenia
- 2011
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Ingår i: Psychiatric Genetics. - : Lippincott Williams & Wilkins. - 0955-8829 .- 1473-5873. ; 21:3, s. 125-131
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: An interaction between predisposing genes and environmental stressors is thought to underlie the neurodevelopmental disorder schizophrenia. In a targeted gene screening, we previously found that the minor allele of the single nucleotide polymorphism (SNP) rs6336 in the neurotrophic tyrosine kinase receptor 1 (NTRK1/TRKA) gene is associated with schizophrenia as a risk factor.METHODS: We genotyped the TRKA SNP in a total of eight independent Caucasian schizophrenia case-control groups.RESULT: Remarkably, although in five of the groups a higher frequency of the risk allele was indeed found in the patients compared with the controls, in the three other groups the SNP acted as a protective factor.CONCLUSION: An intriguing possibility is that this dual character of the TRKA SNP is caused by its interaction with endophenotypic and/or epistatic factors.
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| 9. |
- Wikgren, Mikael, 1981-, et al.
(författare)
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Short Telomeres in Depression and the General Population Are Associated with a Hypocortisolemic State
- 2012
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Ingår i: Biological Psychiatry. - New York : Elsevier. - 0006-3223 .- 1873-2402. ; 71:4, s. 294-300
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Tidskriftsartikel (refereegranskat)abstract
- Background The hypothalamic-pituitary-adrenal (HPA) axis plays a central role in stress regulation, and leukocyte telomere length (TL) has been suggested to represent a cumulative measure of stress. Depression is intimately related with stress and frequently exhibits a dysregulated HPA axis. We aimed to study the relationships between TL and biological and psychological facets of stress in recurrent major depressive disorder and controls. Methods Leukocyte TL was measured in 91 subjects with recurrent major depressive disorder and 451 control subjects. Stress was assessed from both a biological perspective, by assessing HPA axis function with a weight-adjusted very-low-dose dexamethasone suppression test (DST), and a psychological perspective, with self-report questionnaires. Results TL was shorter among patients compared with control subjects (277 base pairs, p = .001). Overall, short TL was associated with a hypocortisolemic state (low post-DST cortisol and high percentage of cortisol reduction after the DST) among both patients and control subjects but more pronounced among patients. This state, which was overrepresented among patients, was characterized by high familial loading of affective disorders among patients (p = .001) and high C-reactive protein levels among control subjects (p = .040). TL was also inversely associated with stress measured with the Perceived Stress Questionnaire (rs = −.258, p = .003). Conclusions Short TL is associated with depression and hypocortisolism. Because hypocortisolism has been shown to develop from chronic stress exposure, our findings corroborate the concept of TL as a cumulative measure of stress and provide novel insights into the detrimental role of stress in depressive illness and the general population.
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