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Ronat, L., Rönnlund, M., Adolfsson, R., Hanganu, A. & Pudas, S. (2024). Revised temperament and character inventory factors predict neuropsychiatric symptoms and aging-related cognitive decline across 25 years. Frontiers in Aging Neuroscience, 16, Article ID 1335336.
Open this publication in new window or tab >>Revised temperament and character inventory factors predict neuropsychiatric symptoms and aging-related cognitive decline across 25 years
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2024 (English)In: Frontiers in Aging Neuroscience, E-ISSN 1663-4365, Vol. 16, article id 1335336Article in journal (Refereed) Published
Abstract [en]

Introduction: Personality traits and neuropsychiatric symptoms such as neuroticism and depression share genetic overlap and have both been identified as risks factors for development of aging-related neurocognitive decline and Alzheimer’s disease (AD). This study aimed to examine revised personality factors derived from the Temperament and Character Inventory, previously shown to be associated with psychiatric disorders, as predictors of neuropsychiatric, cognitive, and brain trajectories of participants from a population-based aging study.

Methods: Mixed-effect linear regression analyses were conducted on data for the full sample (Nmax = 1,286), and a healthy subsample not converting to AD-dementia during 25-year follow-up (Nmax = 1,145), complemented with Cox proportional regression models to determine risk factors for conversion to clinical AD.

Results: Two personality factors, Closeness to Experience (CE: avoidance of new stimuli, high anxiety, pessimistic anticipation, low reward seeking) and Tendence to Liabilities (TL: inability to change, low autonomy, unaware of the value of their existence) were associated with higher levels of depressive symptoms, stress (CE), sleep disturbance (TL), as well as greater decline in memory, vocabulary and verbal fluency in the full sample. Higher CE was additionally associated with greater memory decline across 25 years in the healthy subsample, and faster right hippocampal volume reduction across 8 years in a neuroimaging subsample (N = 216). Most, but not all, personality-cognition associations persisted after controlling for diabetes, hypertension and cardiovascular disease. Concerning risks for conversion to AD, higher age, and APOE-ε4, but none of the personality measures, were significant predictors.

Conclusion: The results indicate that personality traits associated with psychiatric symptoms predict accelerated age-related neurocognitive declines even in the absence of neurodegenerative disease. The attenuation of some personality effects on cognition after adjustment for health indicators suggests that those effects may be partly mediated by somatic health. Taken together, the results further emphasize the importance of personality traits in neurocognitive aging and underscore the need for an integrative (biopsychosocial) perspective of normal and pathological age-related cognitive decline.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2024
Keywords
personality, cognitive decline, neuropsychiatric symptoms, Alzheimer’s dementia, MRI, longitudinal study
National Category
Psychology (excluding Applied Psychology) Neurosciences
Identifiers
urn:nbn:se:umu:diva-221338 (URN)10.3389/fnagi.2024.1335336 (DOI)2-s2.0-85186625892 (Scopus ID)
Funder
Riksbankens Jubileumsfond, 1988-0082:17Riksbankens Jubileumsfond, 2001-0682Swedish Research Council, D1988-0092Swedish Research Council, D1989-0115Swedish Research Council, D1990-0074Swedish Research Council, D1991-0258Swedish Research Council, D1992-0143Swedish Research Council, D1997-0756Swedish Research Council, D1997-1841Swedish Research Council, D1999-0739Swedish Research Council, B1999-474Swedish Research Council, F377/1988-2000Swedish Research Council, 1988-1990:88-0082Swedish Research Council, 311/1991-2000Swedish Research Council, 345-2003-3883Swedish Research Council, 315-2004-6977
Available from: 2024-02-21 Created: 2024-02-21 Last updated: 2024-04-08Bibliographically approved
Eriksson Sörman, D., Åström, E., Ahlström, M., Adolfsson, R. & Körning Ljungberg, J. (2024). The influence of personality traits on engagement in lifelong learning. International Journal of Lifelong Education
Open this publication in new window or tab >>The influence of personality traits on engagement in lifelong learning
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2024 (English)In: International Journal of Lifelong Education, ISSN 0260-1370, E-ISSN 1464-519XArticle in journal (Refereed) Epub ahead of print
Abstract [en]

Today, adult individuals must be able to continuously learn and adapt to the rapid changes occurring in society. However, little is known about the individual characteristics, particularly personality traits, that make adults more likely to engage in learning activities. Moreover, few studies have longitudinally and objectively investigated the influence of personality on engagement in lifelong learning throughout working age. This study therefore used longitudinal data (15 years) to examine which personality traits predicted level and long-term changes in learning activities among 1329 Swedish adults aged 30–60. The results from growth curve modelling showed that over the follow-up period, novelty seeking and self-transcendence were both positively related to overall level of engagement in learning activities, although not to rate of change. Regarding specific activities, novelty seeking was related to higher levels of engagement in attending courses, taking on new education, and making occupational changes, while harm avoidance was negatively related to the likelihood of changing occupation. The results of this study underscore the importance of considering personality in relation to engagement in lifelong learning activities. Insights from this study can potentially increase the likelihood of finding methods to promote lifelong learning, which can be beneficial for educators, policymakers, and companies.

Place, publisher, year, edition, pages
Routledge, 2024
Keywords
Lifelong learning, personality, working age
National Category
Psychology
Identifiers
urn:nbn:se:umu:diva-223775 (URN)10.1080/02601370.2024.2343013 (DOI)
Funder
Vinnova, 2021- 02361
Available from: 2024-04-25 Created: 2024-04-25 Last updated: 2024-04-25
Hess, T., Maj, C., Gehlen, J., Borisov, O., Haas, S. L., Gockel, I., . . . Schumacher, J. (2023). Dissecting the genetic heterogeneity of gastric cancer. EBioMedicine, 92, Article ID 104616.
Open this publication in new window or tab >>Dissecting the genetic heterogeneity of gastric cancer
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2023 (English)In: EBioMedicine, E-ISSN 2352-3964, Vol. 92, article id 104616Article in journal (Refereed) Published
Abstract [en]

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. 

Place, publisher, year, edition, pages
Elsevier, 2023
Keywords
Gastric cancer, Genome-wide association study (GWAS), Oesophageal adenocarcinoma, Transcriptome-wide association study (TWAS)
National Category
Medical Genetics
Identifiers
urn:nbn:se:umu:diva-210278 (URN)10.1016/j.ebiom.2023.104616 (DOI)37209533 (PubMedID)2-s2.0-85159845299 (Scopus ID)
Funder
German Research Foundation (DFG), KN 378/3–1German Research Foundation (DFG), LO 1147/1-1German Research Foundation (DFG), SCHU 1596/6–1German Research Foundation (DFG), VE 917/1-1
Note

Errata: Hess, T., Maj, C., Gehlen, J. et. al. Corrigendum to “Dissecting the genetic heterogeneity of gastric cancer”. eBioMedicine. 2023:94:104709. DOI: 10.1016/j.ebiom.2023.104709

Available from: 2023-06-21 Created: 2023-06-21 Last updated: 2024-04-08Bibliographically approved
Docherty, A. R., Mullins, N., Ashley-Koch, A. E., Qin, X., Coleman, J. R. .., Shabalin, A., . . . Ruderfer, D. M. (2023). GWAS meta-analysis of suicide attempt: identification of 12 genome-wide significant loci and implication of genetic risks for specific health factors. American Journal of Psychiatry, 180(10), 723-738
Open this publication in new window or tab >>GWAS meta-analysis of suicide attempt: identification of 12 genome-wide significant loci and implication of genetic risks for specific health factors
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2023 (English)In: American Journal of Psychiatry, ISSN 0002-953X, E-ISSN 1535-7228, Vol. 180, no 10, p. 723-738Article in journal (Refereed) Published
Abstract [en]

Objective: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and crossvalidated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS metaanalysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.

Methods: This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.

Results: Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.

Conclusions: This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.

Place, publisher, year, edition, pages
American Psychiatric Association Publishing, 2023
National Category
Medical Genetics
Identifiers
urn:nbn:se:umu:diva-219071 (URN)10.1176/appi.ajp.21121266 (DOI)37777856 (PubMedID)2-s2.0-85176353814 (Scopus ID)
Available from: 2024-01-11 Created: 2024-01-11 Last updated: 2024-04-08Bibliographically approved
Josefsson, M., Sundström, A., Pudas, S., Nordin Adolfsson, A., Nyberg, L. & Adolfsson, R. (2023). Memory profiles predict dementia over 23–28 years in normal but not successful aging. International psychogeriatrics, 35(7), 351-359
Open this publication in new window or tab >>Memory profiles predict dementia over 23–28 years in normal but not successful aging
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2023 (English)In: International psychogeriatrics, ISSN 1041-6102, E-ISSN 1741-203X, Vol. 35, no 7, p. 351-359Article in journal (Refereed) Published
Abstract [en]

Objectives: Prospective studies suggest that memory deficits are detectable decades before clinical symptoms of dementia emerge. However, individual differences in long-term memory trajectories prior to diagnosis need to be further elucidated. The aim of the current study was to investigate long-term dementia and mortality risk for individuals with different memory trajectory profiles in a well-characterized population-based sample.

Methods: 1062 adults (aged 45–80 years) who were non-demented at baseline were followed over 23–28 years. Dementia and mortality risk were studied for three previously classified episodic memory trajectory groups: maintained high performance (Maintainers; 26%), average decline (Averages; 64%), and accelerated decline (Decliners; 12%), using multistate modeling to characterize individuals’ transitions from an initial non-demented state, possibly to a state of dementia and/or death.

Results: The memory groups showed considerable intergroup variability in memory profiles, starting 10–15 years prior to dementia diagnosis, and prior to death. A strong relationship between memory trajectory group and dementia risk was found. Specifically, Decliners had more than a fourfold risk of developing dementia compared to Averages. In contrast, Maintainers had a 2.6 times decreased dementia risk compared to Averages, and in addition showed no detectable memory decline prior to dementia diagnosis. A similar pattern of association was found for the memory groups and mortality risk, although only among non-demented.

Conclusion: There was a strong relationship between accelerated memory decline and dementia, further supporting the prognostic value of memory decline. The intergroup differences, however, suggest that mechanisms involved in successful memory aging may delay symptom onset.

Place, publisher, year, edition, pages
Cambridge University Press, 2023
Keywords
memory decline, episodic memory, death, competing risk, multistate model
National Category
Psychology (excluding Applied Psychology)
Identifiers
urn:nbn:se:umu:diva-165499 (URN)10.1017/S1041610219001844 (DOI)31762427 (PubMedID)2-s2.0-85163913454 (Scopus ID)
Available from: 2019-11-25 Created: 2019-11-25 Last updated: 2024-04-08Bibliographically approved
Andersson, J., Sundström, A., Nordin, M., Segersson, D., Forsberg, B., Adolfsson, R. & Oudin, A. (2023). Pm2.5 and dementia in a low exposure setting: the influence of odor identification ability and APOE. Journal of Alzheimer's Disease, 92(2), 679-689
Open this publication in new window or tab >>Pm2.5 and dementia in a low exposure setting: the influence of odor identification ability and APOE
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2023 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 92, no 2, p. 679-689Article in journal (Refereed) Published
Abstract [en]

Background: Growing evidence show that long term exposure to air pollution increases the risk of dementia.

Objective: The aim of this study was to investigate associations between PM2.5 exposure and dementia in a low exposure area, and to investigate the role of olfaction and the APOE ε4 allele in these associations.

Methods: Data were drawn from the Betula project, a longitudinal study on aging, memory, and dementia in Sweden. Odor identification ability was assessed using the Scandinavian Odor Identification Test (SOIT). Annual mean PM2.5 concentrations were obtained from a dispersion-model and matched at the participants’ residential address. Proportional hazard regression was used to calculate hazard ratios.

Results: Of 1,846 participants, 348 developed dementia during the 21-year follow-up period. The average annual mean PM2.5 exposure at baseline was 6.77 µg/m3, which is 1.77 µg/m3 above the WHO definition of clean air. In a fully adjusted model (adjusted for age, sex, APOE, SOIT, cardiovascular diseases and risk factors, and education) each 1 µg/m3 difference in annual mean PM2.5-concentration was associated with a hazard ratio of 1.23 for dementia (95% CI: 1.01–1.50). Analyses stratified by APOE status (ε4 carriers versus non-carriers), and odor identification ability (high versus low), showed associations only for ε4 carriers, and for low performance on odor identification ability.

Conclusion: PM2.5 was associated with an increased risk of dementia in this low pollution setting. The associations between PM2.5 and dementia seemed stronger in APOE carriers and those with below average odor identification ability.

Place, publisher, year, edition, pages
IOS Press, 2023
Keywords
Alzheimer’s disease, Apolipoprotein E, olfaction, particulate matter, vascular dementia
National Category
Occupational Health and Environmental Health
Research subject
Psychology; Occupational and Environmental Medicine
Identifiers
urn:nbn:se:umu:diva-205123 (URN)10.3233/jad-220469 (DOI)000952023800024 ()36776047 (PubMedID)2-s2.0-85151044242 (Scopus ID)
Funder
EU, Horizon 2020, 814978-2Swedish Research Council Formas, 942-2015-1099
Available from: 2023-02-23 Created: 2023-02-23 Last updated: 2024-04-08Bibliographically approved
Schäfer Hackenhaar, F., Josefsson, M., Nordin Adolfsson, A., Landfors, M., Kauppi, K., Porter, T., . . . the Australian Imaging Biomarkers and Lifestyle Study, . (2023). Sixteen-year longitudinal evaluation of blood-based DNA methylation biomarkers for early prediction of Alzheimer’s disease. Journal of Alzheimer's Disease, 94(4), 1443-1464
Open this publication in new window or tab >>Sixteen-year longitudinal evaluation of blood-based DNA methylation biomarkers for early prediction of Alzheimer’s disease
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2023 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 94, no 4, p. 1443-1464Article in journal (Refereed) Published
Abstract [en]

Background: DNA methylation (DNAm), an epigenetic mark reflecting both inherited and environmental influences, hasshown promise for Alzheimer’s disease (AD) prediction.Objective: Testing long-term predictive ability (>15 years) of existing DNAm-based epigenetic age acceleration (EAA)measures and identifying novel early blood-based DNAm AD-prediction biomarkers.

Methods: EAA measures calculated from Illumina EPIC data from blood were tested with linear mixed-effects models(LMMs) in a longitudinal case-control sample (50 late-onset AD cases; 51 matched controls) with prospective data up to 16years before clinical onset, and post-onset follow-up. NovelDNAmbiomarkers were generated with epigenome-wide LMMs,and Sparse Partial Least Squares Discriminant Analysis applied at pre- (10–16 years), and post-AD-onset time-points.

Results: EAA did not differentiate cases from controls during the follow-up time (p > 0.05). Three new DNA biomarkersshowed in-sample predictive ability on average 8 years pre-onset, after adjustment for age, sex, and white blood cell proportions(p-values: 0.022-<0.00001). Our longitudinally-derived panel replicated nominally (p = 0.012) in an external cohort (n = 146cases, 324 controls). However, its effect size and discriminatory accuracy were limited compared to APOE 4-carriership(OR = 1.38 per 1 SD DNAmscore increase versus OR= 13.58 for 4-allele carriage; AUCs = 77.2% versus 87.0%). Literaturereview showed low overlap (n = 4) across 3275 AD-associated CpGs from 8 published studies, and no overlap with ouridentified CpGs.

Conclusion: The limited predictive value of EAA for AD extends prior findings by considering a longer follow-up time, andwith appropriate control for age, sex, APOE, and blood-cell proportions. Results also highlight challenges with replicatingdiscriminatory or predictive CpGs across studies.

Place, publisher, year, edition, pages
IOS Press, 2023
Keywords
Alzheimer’s disease, biomarkers, DNA methylation, epigenomics, longitudinal studies
National Category
Other Basic Medicine
Identifiers
urn:nbn:se:umu:diva-214007 (URN)10.3233/jad-230039 (DOI)37393498 (PubMedID)2-s2.0-85168428453 (Scopus ID)
Funder
Swedish Research Council, 2018-01729The Kempe Foundations, JCK-1922.1
Available from: 2023-09-02 Created: 2023-09-02 Last updated: 2024-04-08Bibliographically approved
Salami, A., Adolfsson, R., Andersson, M., Blennow, K., Lundquist, A., Nordin Adolfsson, A., . . . Nyberg, L. (2022). Association of APOE ɛ4 and Plasma p-tau181 with Preclinical Alzheimer's Disease and Longitudinal Change in Hippocampus Function. Journal of Alzheimer's Disease, 85(3), 1309-1320
Open this publication in new window or tab >>Association of APOE ɛ4 and Plasma p-tau181 with Preclinical Alzheimer's Disease and Longitudinal Change in Hippocampus Function
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2022 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 85, no 3, p. 1309-1320Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The Apolipoprotein E (APOE) ɛ4 allele has been linked to increased tau phosphorylation and tangle formation. APOE ɛ4 carriers with elevated tau might be at the higher risk for Alzheimer's disease (AD) progression. Previous studies showed that tau pathology begins early in areas of the medial temporal lobe. Similarly, APOE ɛ4 carriers showed altered hippocampal functional integrity. However, it remains unknown whether the influence of elevated tau accumulation on hippocampal functional changes would be more pronounced for APOE ɛ4 carriers.

OBJECTIVE: We related ɛ4 carriage to levels of plasma phosphorylated tau (p-tau181) up to 15 years prior to AD onset. Furthermore, elevated p-tau181 was explored in relation to longitudinal changes in hippocampal function and connectivity.

METHODS: Plasma p-tau181 was analyzed in 142 clinically defined AD cases and 126 matched controls. The longitudinal analysis involved 87 non-demented individuals (from population-based study) with two waves of plasma samples and three waves of functional magnetic resonance imaging during rest and memory encoding.

RESULTS: Increased p-tau181 was observed for both ɛ4 carriers and non-carriers close to AD onset, but exclusively for ɛ4 carriers in the early preclinical groups (7- and 13-years pre-AD). In ɛ4 carriers, longitudinal p-tau181 increase was paralleled by elevated local hippocampal connectivity at rest and subsequent reduction of hippocampus encoding-related activity.

CONCLUSION: Our findings support an association of APOE ɛ4 and p-tau181 with preclinical AD and hippocampus functioning.

Place, publisher, year, edition, pages
IOS Press, 2022
Keywords
Alzheimer’s disease, APOE, fMRI, hippocampus, longitudinal, magnetic resonance imaging, p-tau181, phosphorylated tau, population-based
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-192513 (URN)10.3233/JAD-210673 (DOI)000752449800030 ()34924376 (PubMedID)2-s2.0-85124174700 (Scopus ID)
Available from: 2022-02-22 Created: 2022-02-22 Last updated: 2024-04-08Bibliographically approved
Lassas, A., Norrbäck, K.-F., Adolfsson, R. & Maripuu, M. (2022). Bipolar disorder and bone mineral density z-scores in relation to clinical characteristics and lithium medication. Journal of Clinical Medicine, 11(23), Article ID 7158.
Open this publication in new window or tab >>Bipolar disorder and bone mineral density z-scores in relation to clinical characteristics and lithium medication
2022 (English)In: Journal of Clinical Medicine, E-ISSN 2077-0383, Vol. 11, no 23, article id 7158Article in journal (Refereed) Published
Abstract [en]

Bipolar disorder is associated with a long range of medical comorbidities, including migraine, diabetes, and cardiovascular disease. Bipolar disorder has also been associated with an increased risk of bone fractures. Osteoporosis is a reduction in bone mineral density, which leads to an increased risk for fragility fractures. Currently there is limited research on the association between bipolar disorder and osteoporosis. We aimed to study the association between high and low bone mineral density in relation to disease and treatment history in a sample of bipolar patients. We found that bipolar patients with high bone mineral density were more often on lithium medication, had a more active lifestyle and expressed lower current disease burden. Low mineral density was not associated with any of the addressed aspects of disease and treatment history. In conclusion our results support that patients on lithium treatment have higher bone mineral density; further studies are needed to address if lithium medication causes an increase in bone mineral density, and lowers the risk of bone fractures in bipolar disorder.

Place, publisher, year, edition, pages
MDPI, 2022
Keywords
bipolar disorder, disease burden, lithium, osteoporosis
National Category
Endocrinology and Diabetes Orthopaedics
Identifiers
urn:nbn:se:umu:diva-203327 (URN)10.3390/jcm11237158 (DOI)000896269700001 ()36498732 (PubMedID)2-s2.0-85143629611 (Scopus ID)
Funder
Swedish Research Council, 2006-4472Swedish Research Council, 2009-5269Region Jämtland HärjedalenRegion VästerbottenNorrbotten County Council
Available from: 2023-01-18 Created: 2023-01-18 Last updated: 2024-04-08Bibliographically approved
Mullins, N., Kang, J., Campos, A. I., Coleman, J. R. I., Edwards, A. C., Galfalvy, H., . . . Ruderfer, D. M. (2022). Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors. Biological Psychiatry, 91(3), 313-327
Open this publication in new window or tab >>Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
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2022 (English)In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 91, no 3, p. 313-327Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.

METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.

RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.

CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.

Place, publisher, year, edition, pages
Elsevier, 2022
Keywords
Genetic correlation, Genome-wide association study, Pleiotropy, Polygenicity, Suicide, Suicide attempt
National Category
Psychiatry
Identifiers
urn:nbn:se:umu:diva-197707 (URN)10.1016/j.biopsych.2021.05.029 (DOI)000746060000012 ()34861974 (PubMedID)2-s2.0-85119273569 (Scopus ID)
Available from: 2022-07-04 Created: 2022-07-04 Last updated: 2024-04-08Bibliographically approved
Projects
Molecular genetics/genomics of affective and schizophrenic disorders in the isolated Northern Swedish population [2009-05269_VR]; Umeå University
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-9785-8473

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