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Sökning: WFRF:(Nordin Adolfsson Annelie)

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1.
  • Stahl, Eli A, et al. (författare)
  • Genome-wide association study identifies 30 loci associated with bipolar disorder
  • 2019
  • Ingår i: Nature Genetics. - 1061-4036. ; 51:5, s. 793-803
  • Tidskriftsartikel (refereegranskat)abstract
    • Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P < 1 × 10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P < 5 × 10-8) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder.
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2.
  • Oudin, Anna, et al. (författare)
  • Traffic-Related Air Pollution and Dementia Incidence in Northern Sweden A Longitudinal Study
  • 2016
  • Ingår i: Journal of Environmental Health Perspectives. - 0091-6765. ; 124:3, s. 306-312
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Exposure to ambient air pollution is suspected to cause cognitive effects, but a prospective cohort is needed to study exposure to air pollution at the home address and the incidence of dementia.OBJECTIVES: We aimed to assess the association between long-term exposure to traffic-related air pollution and dementia incidence in a major city in northern Sweden.METHODS: Data on dementia incidence over a 15-year period were obtained from the longitudinal Betula study. Traffic air pollution exposure was assessed with a Land Use Regression Model with a spatial resolution of 50 m x 50 m. Annual mean nitrogen oxide levels at the residential address of the participants at baseline (the start of follow-up) was used as a marker for long-term exposure to air pollution.RESULTS: Out of 1806 participants at baseline, 191 were diagnosed with Alzheimer's disease during follow-up, and 111 were diagnosed with vascular dementia. Participants in the highest exposure group were more likely to be diagnosed with dementia (Alzheimer's disease or vascular dementia), with a Hazard Ratio (HR) of 1.43 (95% Confidence Interval (CI): 0.998, 2.05 for the highest versus lowest quartile). The estimates were similar for Alzheimer's disease (HR 1.38) and vascular dementia (HR 1.47). The HR for dementia associated for the third quartile versus the lowest quartile was 1.48 (95% CI: 1.03, 2.11). A sub-analysis that excluded a younger sample that had been re-tested after only 5 years of follow-up suggested stronger associations with exposure than in the full cohort (HR = 1.71; 95% CI: 1.08, 2.73 for the highest versus lowest quartile).CONCLUSIONS: If the associations we observed are causal, then air pollution from traffic might be an important risk factor for vascular dementia and Alzheimer's disease.
3.
4.
  • Stomby, Andreas, et al. (författare)
  • Higher diurnal salivary cortisol levels are related to smaller prefrontal cortex surface area in elderly men and women
  • 2016
  • Ingår i: European Journal of Endocrinology. - 0804-4643. ; 175:2, s. 117-126
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Elevated cortisol levels with aging have been associated with atrophy of the hippocampus and prefrontal cortex (PFC), as well as with impaired cognitive functions in men. However, coexisting diseases have confounded many studies examining these relationships. Studies in women are lacking. Our objective was to test whether salivary cortisol levels were related to morphology of the hippocampus and the PFC, and to cognitive performance. Design: A cross-sectional study including 200 elderly (55-80 years old) men and women. Method: We used magnetic resonance imaging, tests of episodic-, semantic-, and working memory, visuospatial ability, and cortisol levels in four saliva samples collected during 1 day. Results: Area under the curve (AUC) for cortisol levels was negatively related to cortical surface area of the left anterior cingulate gyrus (caudal P < 0.001; rostral P = 0.006), right lateral orbitofrontal cortex (P = 0.004), and right rostral middle frontal gyrus (P = 0.003). In women, there was also a negative relationship with cortical surface area in the left rostral middle frontal gyrus (P = 0.006). No relationship was found between cortisol levels and hippocampal volume. Conclusion: This study suggests that the structure of the medial PFC is related to cortisol levels in both elderly women and men.
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5.
  • Ekström, Ingrid, et al. (författare)
  • Smell Loss Predicts Mortality Risk Regardless of Dementia Conversion
  • 2017
  • Ingår i: Journal of The American Geriatrics Society. - 0002-8614. ; 65:6, s. 1238-1243
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectivesTo determine whether dementia could explain the association between poor olfactory performance and mortality risk within a decade-long follow-up period.DesignProspective cohort study.SettingBetula Study, Umeå, Sweden.ParticipantsA population-based sample of adult participants without dementia at baseline aged 40 to 90 (N = 1,774).MeasurementsOlfactory performance using the Scandinavian Odor-Identification Test (SOIT) and self-reported olfactory function; several social, cognitive, and medical risk factors at baseline; and incident dementia during the following decade.ResultsWithin the 10-year follow-up, 411 of 1,774 (23.2%) participants had died. In a Cox model, the association between higher SOIT score and lower mortality was significant (hazard ratio (HR) = 0.74 per point interval, 95% confidence interval (CI) = 0.71-0.77, P < .001). The effect was attenuated, but remained significant, after controlling for age, sex, education, and health-related and cognitive variables (HR = 0.92, 95% CI = 0.87-0.97, P = .001). The association between SOIT score and mortality was retained after controlling for dementia conversion before death (HR = 0.92, 95% CI = 0.87-0.97, P = .001). Similar results were obtained for self-reported olfactory dysfunction.ConclusionPoor odor identification and poor self-reported olfactory function are associated with greater likelihood of future mortality. Dementia does not attenuate the association between olfactory loss and mortality, suggesting that olfactory loss might mark deteriorating health, irrespective of dementia.
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6.
  • Huckins, Laura M., et al. (författare)
  • Gene expression imputation across multiple brain regions provides insights into schizophrenia risk
  • 2019
  • Ingår i: Nature genetics. - 1546-1718. ; 51:4, s. 659-
  • Tidskriftsartikel (refereegranskat)abstract
    • Transcriptomic imputation approaches combine eQTL reference panels with large-scale genotype data in order to test associations between disease and gene expression. These genic associations could elucidate signals in complex genome-wide association study (GWAS) loci and may disentangle the role of different tissues in disease development. We used the largest eQTL reference panel for the dorso-lateral prefrontal cortex (DLPFC) to create a set of gene expression predictors and demonstrate their utility. We applied DLPFC and 12 GTEx-brain predictors to 40,299 schizophrenia cases and 65,264 matched controls for a large transcriptomic imputation study of schizophrenia. We identified 413 genic associations across 13 brain regions. Stepwise conditioning identified 67 non-MHC genes, of which 14 did not fall within previous GWAS loci. We identified 36 significantly enriched pathways, including hexosaminidase-A deficiency, and multiple porphyric disorder pathways. We investigated developmental expression patterns among the 67 non-MHC genes and identified specific groups of pre- and postnatal expression.
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7.
  • Larsson, Maria, et al. (författare)
  • Loss of Olfactory Function Predicts Mortality Irrespective of Dementia Conversion : 10-year follow-up of an age-varied sample
  • 2016
  • Ingår i: Chemical Senses. - 0379-864X. ; 41:9, s. e111-e288
  • Tidskriftsartikel (refereegranskat)abstract
    • The objective of this study was to examine the association between performance in odor identification and future mortality in a community cohort of adults aged between 40 and 90 years. We assessed olfactory performance with a 13-item-version of the Scandinavian Odor Identification Test (SOIT). The results showed that during follow-up (mean=9.4 years, standard deviation=2.23), 411 of 1774 (23.2%) participants died. In a Cox model, the association between higher SOIT score and mortality was highly significant (hazard ratio [HR]=0.74, per point interval, 95% confidence interval [CI]=0.71–0.77, p<0.001). The effect was attenuated, but remained significant after controlling for age, sex, education, and health and cognitive variables that were also associated with an increased risk of mortality (HR=0.92, 95% CI=0.87–0.97, p=0.001). Controlling for dementia conversion prior to death did not attenuate the association between SOIT score and mortality (HR=0.92, 95% CI=0.87–0.97, p=0.001). Similar results were obtained for olfactory sensitivity as assessed by self-report. Overall, the present findings show that poor odor identification performance is associated with an increased likelihood of future mortality in middle-aged and older adults, after controlling for social, cognitive, and medical risk factors. Most importantly, controlling for the development of dementia did not attenuate the association between odor identification and mortality, suggesting that olfactory decline might mark deteriorating health also irrespective of dementia.
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8.
  • Olofsson, Jonas K., et al. (författare)
  • Long-term episodic memory decline is associated with olfactory deficits only in carriers of ApoE-є4
  • 2016
  • Ingår i: Neuropsychologia. - Elsevier. - 0028-3932. ; 85, s. 1-9
  • Tidskriftsartikel (refereegranskat)abstract
    • The ɛ4 allele of the Apolipoprotein E gene is a genetic risk factor for late-onset dementia of the Alzheimers' type (DAT), which is characterized by loss of both episodic memory and olfactory functions. Little is known about the possible role of ɛ4 in the association between ongoing episodic memory decline and olfactory deficits in the general population, but such information is relevant in determining the relevance of olfaction as a marker of DAT risk. The present study was based on a large, population-based sample (n=1087, aged 45-90 years, of which 324 were ɛ4-carriers). Episodic memory change rates were established using data collected every 5 years for a 10-20 year interval leading up to an olfactory assessment using the Scandinavian Odor Identification Test at the last wave of data collection. Participants were classified according to whether or not their episodic memory ability declined more rapidly than the age-typical norm (by > 1SD). Our main result is that only in ɛ4-carriers was episodic memory decline associated with odor identification impairment. In individuals without ɛ4, odor identification was unrelated to episodic memory decline status. Follow-up analyses indicated that this moderation by ɛ4 was due to the olfactory nature of the identification test, and that the effect was not caused by 63 individuals with dementia. Our results suggest that the ɛ4 determines the functional association between ongoing episodic memory decline and olfaction. These findings are consistent with the notion that ɛ4-carriers with DAT, compared to non-carriers, display a cortical atrophy pattern that is more focused on mediotemporal lobe regions supporting olfactory and episodic memory functions. Olfactory and memory assessments might provide complementary information on mediotemporal atrophy prior to clinical dementia onset, but the ɛ4 should be considered when using olfactory assessment as an early-stage indicator.
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9.
  • Szatkiewicz, Jin, et al. (författare)
  • The genomics of major psychiatric disorders in a large pedigree from Northern Sweden
  • 2019
  • Ingår i: Translational Psychiatry. - Nature Publishing Group. - 2158-3188. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • We searched for genetic causes of major psychiatric disorders (bipolar disorder, schizoaffective disorder, and schizophrenia) in a large, densely affected pedigree from Northern Sweden that originated with three pairs of founders born around 1650. We applied a systematic genomic approach to the pedigree via karyotyping (N = 9), genome-wide SNP arrays (N = 418), whole-exome sequencing (N = 26), and whole-genome sequencing (N = 10). Comprehensive analysis did not identify plausible variants of strong effect. Rather, pedigree cases had significantly higher genetic risk scores compared to pedigree and community controls.
10.
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