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Publications (10 of 30) Show all publications
Karlsson, I. K., Lehto, K., Reynolds, C. A. & Dahl Aslan, A. K. (2019). Age-Dependent Effects Of Body Mass Index On The Risk Of Dementia. European Neuropsychopharmacology, 29(Suppl. 5), S180-S181, Article ID M26.
Open this publication in new window or tab >>Age-Dependent Effects Of Body Mass Index On The Risk Of Dementia
2019 (English)In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 29, no Suppl. 5, p. S180-S181, article id M26Article in journal, Meeting abstract (Refereed) Published
Place, publisher, year, edition, pages
Elsevier, 2019
National Category
Neurology
Identifiers
urn:nbn:se:hj:diva-46744 (URN)10.1016/j.euroneuro.2019.08.126 (DOI)000488216600326 ();HHJARNIS (Local ID);HHJARNIS (Archive number);HHJARNIS (OAI)
Note

27th World Congress of Psychiatric Genetics (WCPG), Los Angeles, CA, OCT 26-31, 2019

Available from: 2019-10-29 Created: 2019-10-29 Last updated: 2019-10-29Bibliographically approved
Wang, Y., Karlsson, R., Jylhävä, J., Hedman, Å. K., Almqvist, C., Karlsson, I. K., . . . Hägg, S. (2019). Comprehensive longitudinal study of epigenetic mutations in aging. Clinical Epigenetics, 11, Article ID 187.
Open this publication in new window or tab >>Comprehensive longitudinal study of epigenetic mutations in aging
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2019 (English)In: Clinical Epigenetics, E-ISSN 1868-7083, Vol. 11, article id 187Article in journal (Refereed) Published
Abstract [en]

Background: The role of DNA methylation in aging has been widely studied. However, epigenetic mutations, here defined as aberrant methylation levels compared to the distribution in a population, are less understood. Hence, we investigated longitudinal accumulation of epigenetic mutations, using 994 blood samples collected at up to five time points from 375 individuals in old ages.

Results: We verified earlier cross-sectional evidence on the increase of epigenetic mutations with age, and identified important contributing factors including sex, CD19+ B cells, genetic background, cancer diagnosis, and technical artifacts. We further classified epigenetic mutations into High/Low Methylation Outliers (HMO/LMO) according to their changes in methylation, and specifically studied methylation sites (CpGs) that were prone to mutate (frequently mutated CpGs). We validated four epigenetically mutated CpGs using pyrosequencing in 93 samples. Furthermore, by using twins, we concluded that the age-related accumulation of epigenetic mutations was not related to genetic factors, hence driven by stochastic or environmental effects.

Conclusions: Here we conducted a comprehensive study of epigenetic mutation and highlighted its important role in aging process and cancer development. 

Place, publisher, year, edition, pages
BioMed Central, 2019
Keywords
Aging, Cancer, Epigenetic mutation, Twin study, adult, article, artifact, B lymphocyte, cancer diagnosis, epigenetics, female, genetic background, human, human cell, human experiment, human tissue, longitudinal study, major clinical study, male, methylation, pyrosequencing, stochastic model
National Category
Cancer and Oncology Medical Genetics
Identifiers
urn:nbn:se:hj:diva-47209 (URN)10.1186/s13148-019-0788-9 (DOI)000510643900001 ()31818313 (PubMedID)2-s2.0-85076285980 (Scopus ID)GOA HHJ 2019 (Local ID)GOA HHJ 2019 (Archive number)GOA HHJ 2019 (OAI)
Funder
EU, Horizon 2020, 634821Forte, Swedish Research Council for Health, Working Life and Welfare, 97:0147:1B, 2009-0795, 2013-2292Swedish Research Council, 825-2007-7460, 825-2009-6141, 521-2013-8689, 2015-03255, 2015-06796The Karolinska Institutet's Research Foundation
Available from: 2020-01-02 Created: 2020-01-02 Last updated: 2020-02-13Bibliographically approved
Karlsson, I. K., Ericsson, M., Wang, Y., Jylhävä, J., Hägg, S., Pedersen, N. L., . . . Dahl Aslan, A. K. (2019). DNA methylation and body mass index during late-life - a longitudinal twin study. In: : . Paper presented at International Association of Gerontology and Geriatrics European Region Congress 2019, 23rd – 25th May 2019, Gothenburg, Sweden.
Open this publication in new window or tab >>DNA methylation and body mass index during late-life - a longitudinal twin study
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2019 (English)Conference paper, Poster (with or without abstract) (Refereed)
National Category
Gerontology, specialising in Medical and Health Sciences
Identifiers
urn:nbn:se:hj:diva-43780 (URN)
Conference
International Association of Gerontology and Geriatrics European Region Congress 2019, 23rd – 25th May 2019, Gothenburg, Sweden
Available from: 2019-05-27 Created: 2019-05-27 Last updated: 2019-05-27Bibliographically approved
Karlsson, I. K., Ericsson, M., Wang, Y., Jylhava, J., Hagg, S., Dahl Aslan, A. K., . . . Pedersen, N. L. (2019). DNA methylation and change in late-life cognitive abilities. Paper presented at 49th Annual Meeting of the Behavior-Genetics-Association (BGA), June 26-29, 2019, Karolinska Institute, Stockholm, Sweden. Behavior Genetics, 49(6), 503-503
Open this publication in new window or tab >>DNA methylation and change in late-life cognitive abilities
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2019 (English)In: Behavior Genetics, ISSN 0001-8244, E-ISSN 1573-3297, Vol. 49, no 6, p. 503-503Article in journal, Meeting abstract (Refereed) Published
Place, publisher, year, edition, pages
Springer, 2019
National Category
Medical Genetics Gerontology, specialising in Medical and Health Sciences
Identifiers
urn:nbn:se:hj:diva-47171 (URN)000494050500064 ()
Conference
49th Annual Meeting of the Behavior-Genetics-Association (BGA), June 26-29, 2019, Karolinska Institute, Stockholm, Sweden
Available from: 2019-12-18 Created: 2019-12-18 Last updated: 2019-12-18Bibliographically approved
Lehto, K., Karlsson, I. K., Gatz, M. & Pedersen, N. L. (2019). Does depression in old age reflect prodromal dementia? A polygenic risk score approach. Paper presented at 49th Annual Meeting of the Behavior-Genetics-Association (BGA), June 26-29, 2019, Karolinska Institute, Stockholm, SWEDEN. Behavior Genetics, 49(6), 512-512
Open this publication in new window or tab >>Does depression in old age reflect prodromal dementia? A polygenic risk score approach
2019 (English)In: Behavior Genetics, ISSN 0001-8244, E-ISSN 1573-3297, Vol. 49, no 6, p. 512-512Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Springer, 2019
National Category
Gerontology, specialising in Medical and Health Sciences
Identifiers
urn:nbn:se:hj:diva-47170 (URN)000494050500093 ()
Conference
49th Annual Meeting of the Behavior-Genetics-Association (BGA), June 26-29, 2019, Karolinska Institute, Stockholm, SWEDEN
Available from: 2019-12-18 Created: 2019-12-18 Last updated: 2019-12-18Bibliographically approved
Lehto, K., Karlsson, I. K., Gatz, M. & Pedersen, N. L. (2019). Does depression in old age reflect prodromal dementia? A polygenic risk score approach in two longitudinal studies. European Neuropsychopharmacology, 29(5 Suppl.), S181-S182
Open this publication in new window or tab >>Does depression in old age reflect prodromal dementia? A polygenic risk score approach in two longitudinal studies
2019 (English)In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 29, no 5 Suppl., p. S181-S182Article in journal, Meeting abstract (Refereed) Published
Place, publisher, year, edition, pages
Elsevier, 2019
National Category
Neurology
Identifiers
urn:nbn:se:hj:diva-46745 (URN)10.1016/j.euroneuro.2019.08.128 (DOI)000488216600328 ();HHJARNIS (Local ID);HHJARNIS (Archive number);HHJARNIS (OAI)
Note

27th World Congress of Psychiatric Genetics (WCPG), Los Angeles, CA, USA, October 26-31, 2019

Available from: 2019-10-29 Created: 2019-10-29 Last updated: 2019-12-18Bibliographically approved
Kodesh, A., Sandin, S., Reichenberg, A., Rotstein, A., Pedersen, N. L., Ericsson, M., . . . Levine, S. Z. (2019). Exposure to antidepressant medication and the risk of incident dementia. The American journal of geriatric psychiatry, 27(11), 1177-1188
Open this publication in new window or tab >>Exposure to antidepressant medication and the risk of incident dementia
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2019 (English)In: The American journal of geriatric psychiatry, ISSN 1064-7481, E-ISSN 1545-7214, Vol. 27, no 11, p. 1177-1188Article in journal (Refereed) Published
Abstract [en]

Objective: To test competing hypotheses that monotherapeutic antidepressant exposure is associated with an increased versus a decreased risk of dementia.

Methods: A prospective national matched cohort study from Israel (N = 71,515) without dementia (2002–2012) aged 60 and over were followed up for incident dementia from May 2013 to October 2017. Exposure to antidepressant monotherapy was classified with Anatomical Therapeutic Chemical Codes (N06A) from January 1, 2013 to December 31, 2016. The association between antidepressant monotherapy and the risk of incident dementia was quantified with hazard ratios (HR) and their 95% confidence intervals (CI) obtained from Cox regression models unadjusted and adjusted for 42 covariates. The robustness of the results was tested with 24 sensitivity analyses: 19 analyses restricted to subsamples with plausible differential dementia risks (e.g., anxiety and depression), and 5 analyses across and within antidepressant drug classes.

Results: In the primary analysis, the risk of incident dementia for the group exposed to antidepressant monotherapy compared to the group unexposed to antidepressants was estimated with an unadjusted HR = 4.09 (df = 1, 95% Wald CI = 3.64, 4.60) and an adjusted HR = 3.43 (df = 1, 95% Wald CI = 3.04, 3.88). Across the 24 sensitivity analyses the estimated adjusted HR values ranged from 1.99 to 5.47.

Conclusion: In this study, monotherapeutic antidepressant exposure in old age was associated with increased incident dementia. Clinicians, caregivers, and patients may wish to consider this potentially negative consequence of antidepressant exposure and aim to balance the costs and benefits of treatment. 

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
antidepressant medication, Dementia, depression, epidemiology
National Category
Gerontology, specialising in Medical and Health Sciences
Identifiers
urn:nbn:se:hj:diva-45327 (URN)10.1016/j.jagp.2019.05.019 (DOI)000488523100003 ()31235427 (PubMedID)2-s2.0-85067435646 (Scopus ID);HHJARNIS (Local ID);HHJARNIS (Archive number);HHJARNIS (OAI)
Available from: 2019-07-11 Created: 2019-07-11 Last updated: 2019-10-29Bibliographically approved
Jansen, I. E., Savage, J. E., Watanabe, K., Bryois, J., Williams, D. M., Steinberg, S., . . . Posthuma, D. (2019). Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer’s disease risk. Nature Genetics, 51(3), 404-413
Open this publication in new window or tab >>Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer’s disease risk
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2019 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 51, no 3, p. 404-413Article in journal (Refereed) Published
Abstract [en]

Alzheimer’s disease (AD) is highly heritable and recent studies have identified over 20 disease-associated genomic loci. Yet these only explain a small proportion of the genetic variance, indicating that undiscovered loci remain. Here, we performed a large genome-wide association study of clinically diagnosed AD and AD-by-proxy (71,880 cases, 383,378 controls). AD-by-proxy, based on parental diagnoses, showed strong genetic correlation with AD (rg = 0.81). Meta-analysis identified 29 risk loci, implicating 215 potential causative genes. Associated genes are strongly expressed in immune-related tissues and cell types (spleen, liver, and microglia). Gene-set analyses indicate biological mechanisms involved in lipid-related processes and degradation of amyloid precursor proteins. We show strong genetic correlations with multiple health-related outcomes, and Mendelian randomization results suggest a protective effect of cognitive ability on AD risk. These results are a step forward in identifying the genetic factors that contribute to AD risk and add novel insights into the neurobiology of AD. 

Place, publisher, year, edition, pages
Nature Publishing Group, 2019
National Category
Neurology
Identifiers
urn:nbn:se:hj:diva-43026 (URN)10.1038/s41588-018-0311-9 (DOI)000459947200010 ()30617256 (PubMedID)2-s2.0-85059641255 (Scopus ID);HHJARNIS (Local ID);HHJARNIS (Archive number);HHJARNIS (OAI)
Available from: 2019-02-18 Created: 2019-02-18 Last updated: 2019-03-14
Karlsson, I. K., Reynolds, C. A., Escott-Price, V., Hardy, J., Gatz, M. & Pedersen, N. L. (2019). Heritability of Alzheimer's disease – Comparison of twin and polygenic methods. European Neuropsychopharmacology, 29(Suppl. 4), S1208-S1209
Open this publication in new window or tab >>Heritability of Alzheimer's disease – Comparison of twin and polygenic methods
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2019 (English)In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 29, no Suppl. 4, p. S1208-S1209Article in journal, Meeting abstract (Refereed) Published
Place, publisher, year, edition, pages
Elsevier, 2019
National Category
Neurology
Identifiers
urn:nbn:se:hj:diva-45568 (URN)10.1016/j.euroneuro.2018.08.259 (DOI)000477708400341 ()
Available from: 2019-08-15 Created: 2019-08-15 Last updated: 2019-08-15Bibliographically approved
Konki, M., Malonzo, M., Karlsson, I. K., Lindgren, N., Ghimire, B., Smolander, J., . . . Lund, R. J. (2019). Peripheral blood DNA methylation differences in twin pairs discordant for Alzheimer's disease.. Clinical Epigenetics, 11(1), Article ID 130.
Open this publication in new window or tab >>Peripheral blood DNA methylation differences in twin pairs discordant for Alzheimer's disease.
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2019 (English)In: Clinical Epigenetics, E-ISSN 1868-7083, Vol. 11, no 1, article id 130Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Alzheimer's disease results from a neurodegenerative process that starts well before the diagnosis can be made. New prognostic or diagnostic markers enabling early intervention into the disease process would be highly valuable. Environmental and lifestyle factors largely modulate the disease risk and may influence the pathogenesis through epigenetic mechanisms, such as DNA methylation. As environmental and lifestyle factors may affect multiple tissues of the body, we hypothesized that the disease-associated DNA methylation signatures are detectable in the peripheral blood of discordant twin pairs.

RESULTS: Comparison of 23 disease discordant Finnish twin pairs with reduced representation bisulfite sequencing revealed peripheral blood DNA methylation differences in 11 genomic regions with at least 15.0% median methylation difference and FDR adjusted p value ≤ 0.05. Several of the affected genes are primarily associated with neuronal functions and pathologies and do not display disease-associated differences in gene expression in blood. The DNA methylation mark in ADARB2 gene was found to be differentially methylated also in the anterior hippocampus, including entorhinal cortex, of non-twin cases and controls. Targeted bisulfite pyrosequencing of the DNA methylation mark in ADARB2 gene in 62 Finnish and Swedish twin pairs revealed that, in addition to the disease status, DNA methylation of this region is influenced by gender, age, zygosity, APOE genotype, and smoking. Further analysis of 120 Swedish twin pairs indicated that this specific DNA methylation mark is not predictive for Alzheimer's disease and becomes differentially methylated after disease onset.

CONCLUSIONS: DNA methylation differences can be detected in the peripheral blood of twin pairs discordant for Alzheimer's disease. These DNA methylation signatures may have value as disease markers and provide insights into the molecular mechanisms of pathogenesis. We found no evidence that the DNA methylation marks would be associated with gene expression in blood. Further studies are needed to elucidate the potential importance of the associated genes in neuronal functions and to validate the prognostic or diagnostic value of the individual marks or marker panels.

Place, publisher, year, edition, pages
BMC, 2019
Keywords
Alzheimer’s disease, DNA methylome, Hippocampus, Peripheral blood, Twin pair
National Category
Medical Genetics
Identifiers
urn:nbn:se:hj:diva-46223 (URN)10.1186/s13148-019-0729-7 (DOI)000483656100001 ()31477183 (PubMedID)2-s2.0-85071753909 (Scopus ID)GOA HHJ 2019;HHJARNIS (Local ID)GOA HHJ 2019;HHJARNIS (Archive number)GOA HHJ 2019;HHJARNIS (OAI)
Available from: 2019-09-17 Created: 2019-09-17 Last updated: 2019-09-17Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-3605-7829

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