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Nordin Adolfsson, Annelie
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Publications (10 of 31) Show all publications
Musliner, K. L., Mortensen, P. B., McGrath, J. J., Suppli, N. P., Hougaard, D. M., Bybjerg-Grauholm, J., . . . Agerbo, E. (2019). Association of Polygenic Liabilities for Major Depression, Bipolar Disorder, and Schizophrenia With Risk for Depression in the Danish Population. JAMA psychiatry, 76(5), 516-525
Open this publication in new window or tab >>Association of Polygenic Liabilities for Major Depression, Bipolar Disorder, and Schizophrenia With Risk for Depression in the Danish Population
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2019 (English)In: JAMA psychiatry, ISSN 2168-6238, E-ISSN 2168-622X, Vol. 76, no 5, p. 516-525Article in journal (Refereed) Published
Abstract [en]

Importance: Although the usefulness of polygenic risk scores as a measure of genetic liability for major depression (MD) has been established, their association with depression in the general population remains relatively unexplored.

Objective: To evaluate whether polygenic risk scores for MD, bipolar disorder (BD), and schizophrenia (SZ) are associated with depression in the general population and explore whether these polygenic liabilities are associated with heterogeneity in terms of age at onset and severity at the initial depression diagnosis.

Design, Setting, and Participants: Participants were drawn from the Danish iPSYCH2012 case-cohort study, a representative sample drawn from the population of Denmark born between May 1, 1981, and December 31, 2005. The hazard of depression was estimated using Cox regressions modified to accommodate the case-cohort design. Case-only analyses were conducted using linear and multinomial regressions. The data analysis was conducted from February 2017 to June 2018.

Exposures: Polygenic risk scores for MD, BD, and SZ trained using the most recent genome-wide association study results from the Psychiatric Genomics Consortium.

Main Outcomes and Measures: The main outcome was first depressive episode (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] code F32) treated in hospital-based psychiatric care. Severity at the initial diagnosis was measured using the ICD-10 code severity specifications (mild, moderate, severe without psychosis, and severe with psychosis) and treatment setting (inpatient, outpatient, and emergency).

Results: Of 34 573 participants aged 10 to 31 years at censoring, 68% of those with depression were female compared with 48.9% of participants without depression. Each SD increase in polygenic liability for MD, BD, and SZ was associated with 30% (hazard ratio [HR], 1.30; 95% CI, 1.27-1.33), 5% (HR, 1.05; 95% CI, 1.02-1.07), and 12% (HR, 1.12; 95% CI, 1.09-1.15) increases in the hazard of depression, respectively. Among cases, a higher polygenic liability for BD was associated with earlier depression onset (β = -.07; SE = .02; P = .002).

Conclusions and Relevance: Polygenic liability for MD is associated with first depression in the general population, which supports the idea that these scores tap into an underlying liability for developing the disorder. The fact that polygenic risk for BD and polygenic risk for SZ also were associated with depression is consistent with prior evidence that these disorders share some common genetic overlap. Variations in polygenic liability may contribute slightly to heterogeneity in clinical presentation, but these associations appear minimal.

Place, publisher, year, edition, pages
Chicago: American Medical Association, 2019
National Category
Psychiatry
Identifiers
urn:nbn:se:umu:diva-160324 (URN)10.1001/jamapsychiatry.2018.4166 (DOI)000467491200013 ()30698613 (PubMedID)
Available from: 2019-06-17 Created: 2019-06-17 Last updated: 2019-09-05Bibliographically approved
Huckins, L. M., Dobbyn, A., Ruderfer, D. M., Hoffman, G., Wang, W., Pardinas, A. F., . . . Sullivan, P. F. (2019). Gene expression imputation across multiple brain regions provides insights into schizophrenia risk. Nature Genetics, 51(4), 659-+
Open this publication in new window or tab >>Gene expression imputation across multiple brain regions provides insights into schizophrenia risk
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2019 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 51, no 4, p. 659-+Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019
National Category
Medical Genetics Genetics
Identifiers
urn:nbn:se:umu:diva-158080 (URN)10.1038/s41588-019-0364-4 (DOI)000462767500013 ()30911161 (PubMedID)
Funder
NIH (National Institute of Health), R01MH085542NIH (National Institute of Health), R01MH093725NIH (National Institute of Health), P50MH066392NIH (National Institute of Health), P50MH080405NIH (National Institute of Health), R01MH097276NIH (National Institute of Health), RO1-MH-075916NIH (National Institute of Health), P50M096891NIH (National Institute of Health), P50MH084053S1NIH (National Institute of Health), R37MH057881NIH (National Institute of Health), R37MH057881S1NIH (National Institute of Health), HHSN271201300031CNIH (National Institute of Health), AG02219NIH (National Institute of Health), AG05138NIH (National Institute of Health), MH06692Novo Nordisk
Available from: 2019-04-15 Created: 2019-04-15 Last updated: 2019-04-15Bibliographically approved
Stahl, E. A., Breen, G., Forstner, A. J., McQuillin, A., Ripke, S., Trubetskoy, V., . . . Sklar, P. (2019). Genome-wide association study identifies 30 loci associated with bipolar disorder. Nature Genetics, 51(5), 793-803
Open this publication in new window or tab >>Genome-wide association study identifies 30 loci associated with bipolar disorder
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2019 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 51, no 5, p. 793-803Article in journal (Refereed) Published
Abstract [en]

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.

National Category
Medical Genetics
Identifiers
urn:nbn:se:umu:diva-159921 (URN)10.1038/s41588-019-0397-8 (DOI)000466842000007 ()31043756 (PubMedID)
Available from: 2019-06-10 Created: 2019-06-10 Last updated: 2019-06-10Bibliographically approved
Figueira, J., Adolfsson, R., Nordin Adolfsson, A., Nyberg, L. & Öhman, A. (2019). Serum Metabolite Markers of Dementia Through Quantitative NMR Analysis: The Importance of Threonine-Linked Metabolic Pathways. Journal of Alzheimer's Disease, 69(3), 763-774
Open this publication in new window or tab >>Serum Metabolite Markers of Dementia Through Quantitative NMR Analysis: The Importance of Threonine-Linked Metabolic Pathways
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2019 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 69, no 3, p. 763-774Article in journal (Refereed) Published
Abstract [en]

There is a great need for diagnostic biomarkers of impending dementia. Metabolite markers in blood have been investigated in several studies, but inconclusive findings encourage further investigation, particularly in the pre-diagnostic phase. In the present study, the serum metabolomes of 110 dementia or pre-diagnostic dementia individuals and 201 healthy individuals matched for age, gender, and education were analyzed by nuclear magnetic resonance spectroscopy in combination with multivariate data analysis. 58 metabolites were quantified in each of the 311 samples. Individuals with dementia were discriminated from controls using a panel of seven metabolites, while the pre-diagnostic dementia subjects were distinguished from controls using a separate set of seven metabolites, where threonine was a common significant metabolite in both panels. Metabolite and pathway alterations specific for dementia and pre-diagnostic dementia were identified, in particular a disturbed threonine catabolism at the pre-diagnostic stage that extends to several threonine-linked pathways at the dementia stage.

Place, publisher, year, edition, pages
IOS Press, 2019
Keywords
Alzheimer's disease, biomarker, dementia, metabolomics/metabonomics, NMR, serum, vascular dementia
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:umu:diva-161551 (URN)10.3233/JAD-181189 (DOI)000471781600013 ()31127768 (PubMedID)
Funder
Knut and Alice Wallenberg FoundationThe Kempe Foundations
Available from: 2019-07-10 Created: 2019-07-10 Last updated: 2019-07-10Bibliographically approved
Crowley, J., Mudgal, P., Nordin Adolfsson, A., Åberg, K., Alaerts, M., Genovese, G., . . . Sullivan, P. (2019). The genomics of bipolar and schizophrenic disorders in a large pedigree from a northern Swedish isolate. Paper presented at 25th World Congress of Psychiatric Genetics (WCPG), OCT 13-17, 2017, Orlando, FL. European Neuropsychopharmacology, 29, S902-S903
Open this publication in new window or tab >>The genomics of bipolar and schizophrenic disorders in a large pedigree from a northern Swedish isolate
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2019 (English)In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 29, p. S902-S903Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Elsevier, 2019
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:umu:diva-158123 (URN)10.1016/j.euroneuro.2017.08.217 (DOI)000462156400346 ()
Conference
25th World Congress of Psychiatric Genetics (WCPG), OCT 13-17, 2017, Orlando, FL
Note

Supplement: 3

Meeting Abstract: SU28

Available from: 2019-04-12 Created: 2019-04-12 Last updated: 2019-04-12Bibliographically approved
Szatkiewicz, J., Crowley, J. J., Nordin Adolfsson, A., Åberg, K. A., Alaerts, M., Genovese, G., . . . Sullivan, P. F. (2019). The genomics of major psychiatric disorders in a large pedigree from Northern Sweden. Translational Psychiatry, 9, Article ID 60.
Open this publication in new window or tab >>The genomics of major psychiatric disorders in a large pedigree from Northern Sweden
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2019 (English)In: Translational Psychiatry, ISSN 2158-3188, E-ISSN 2158-3188, Vol. 9, article id 60Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019
National Category
Psychiatry
Identifiers
urn:nbn:se:umu:diva-157590 (URN)10.1038/s41398-019-0414-9 (DOI)000459834400001 ()30718465 (PubMedID)
Available from: 2019-03-29 Created: 2019-03-29 Last updated: 2019-03-29Bibliographically approved
Oudin, A., Andersson, J., Sundström, A., Nordin Adolfsson, A., Oudin Åström, D., Adolfsson, R., . . . Nordin, M. (2019). Traffic-Related Air Pollution as a Risk Factor for Dementia: No Clear Modifying Effects of APOEɛ4 in the Betula Cohort. Journal of Alzheimer's Disease
Open this publication in new window or tab >>Traffic-Related Air Pollution as a Risk Factor for Dementia: No Clear Modifying Effects of APOEɛ4 in the Betula Cohort
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2019 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908Article in journal (Refereed) Epub ahead of print
Abstract [en]

It is widely known that the apolipoprotein E (APOE) ɛ4 allele imposes a higher risk for Alzheimer’s disease (AD). Recent evidence suggests that exposure to air pollution is also a risk factor for AD, and results from a few studies indicate that the effect of air pollution on cognitive function and dementia is stronger in APOE ɛ4 carriers than in non-carriers. Air pollution and interaction with APOE ɛ4 on AD risk thus merits further attention. We studied dementia incidence over a 15-year period from the longitudinal Betula study in Northern Sweden. As a marker for long-term exposure to traffic-related air pollution, we used modelled annual mean nitrogen oxide levels at the residential address of the participants at start of follow-up. Nitrogen oxide correlate well with fine particulate air pollution levels in the study area. We had full data on air pollution, incidence of AD and vascular dementia (VaD), APOE ɛ4 carrier status, and relevant confounding factors for 1,567 participants. As expected, air pollution was rather clearly associated with dementia incidence. However, there was no evidence for a modifying effect by APOE ɛ4 on the association (p-value for interaction > 0.30 for both total dementia (AD+VaD) and AD). The results from this study do not imply that adverse effects of air pollution on dementia incidence is limited to, or stronger in, APOE ɛ4 carriers than in the total population.

Place, publisher, year, edition, pages
IOS Press, 2019
Keywords
Air pollution, Alzheimer’s disease, apolipoprotein E, dementia
National Category
Occupational Health and Environmental Health
Identifiers
urn:nbn:se:umu:diva-163266 (URN)10.3233/JAD-181037 (DOI)31450491 (PubMedID)
Available from: 2019-09-12 Created: 2019-09-12 Last updated: 2019-09-13
de Jong, S., Abdalla Diniz, M. J., Saloma, A., Gadelha, A., Santoro, M. L., Ota, V. K., . . . Shi, J. (2018). Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder. Communications Biology, 1, Article ID 163.
Open this publication in new window or tab >>Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder
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2018 (English)In: Communications Biology, ISSN 2399-3642, Vol. 1, article id 163Article in journal (Refereed) Published
Abstract [en]

Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.

Place, publisher, year, edition, pages
Nature Publishing Group, 2018
National Category
Psychiatry
Identifiers
urn:nbn:se:umu:diva-157800 (URN)10.1038/s42003-018-0155-y (DOI)000461126500163 ()30320231 (PubMedID)
Available from: 2019-04-02 Created: 2019-04-02 Last updated: 2019-04-02Bibliographically approved
Marshall, C. R., Howrigan, D. P., Merico, D., Thiruvahindrapuram, B., Wu, W., Greer, D. S., . . . Sebat, J. (2017). Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects. Nature Genetics, 49(1), 27-35
Open this publication in new window or tab >>Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects
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2017 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 49, no 1, p. 27-35Article in journal (Refereed) Published
Abstract [en]

Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (odds ratio (OR) = 1.11, P = 5.7 x 10(-15)), which persisted after excluding loci implicated in previous studies (OR = 1.07, P = 1.7 x 10(-6)). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 x 10(-11)) and neurobehavioral phenotypes in mouse (OR = 1.18, P = 7.3 x 10(-5)). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by nonallelic homologous recombination.

National Category
Psychiatry Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-131884 (URN)10.1038/ng.3725 (DOI)000390976600008 ()
Available from: 2017-02-24 Created: 2017-02-24 Last updated: 2018-06-09Bibliographically approved
Degerman, S., Josefsson, M., Nordin Adolfsson, A., Wennstedt, S., Landfors, M., Haider, Z., . . . Adolfsson, R. (2017). Maintained memory in aging is associated with young epigenetic age. Neurobiology of Aging, 55, 167-171
Open this publication in new window or tab >>Maintained memory in aging is associated with young epigenetic age
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2017 (English)In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 55, p. 167-171Article in journal (Refereed) Published
Abstract [en]

Epigenetic alterations during aging have been proposed to contribute to decline in physical and cognitive functions, and accelerated epigenetic aging has been associated with disease and all-cause mortality later in life. In this study, we estimated epigenetic age dynamics in groups with different memory trajectories (maintained high performance, average decline, and accelerated decline) over a 15-year period. Epigenetic (DNA-methylation [DNAm]) age was assessed, and delta age (DNAm age - chronological age) was calculated in blood samples at baseline (age: 55-65 years) and 15 years later in 52 age- and gender-matched individuals from the Betula study in Sweden. A lower delta DNAm age was observed for those with maintained memory functions compared with those with average (p = 0.035) or accelerated decline (p = 0.037). Moreover, separate analyses revealed that DNAm age at follow-up, but not chronologic age, was a significant predictor of dementia (p = 0.019). Our findings suggest that young epigenetic age contributes to maintained memory in aging.

Place, publisher, year, edition, pages
Elsevier, 2017
National Category
Other Basic Medicine
Identifiers
urn:nbn:se:umu:diva-132221 (URN)10.1016/j.neurobiolaging.2017.02.009 (DOI)000405068100018 ()28292535 (PubMedID)
Available from: 2017-03-07 Created: 2017-03-07 Last updated: 2019-05-10Bibliographically approved
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