24 results on '"Bandstein, Marcus"'
Search Results
2. The Role of FTO and Vitamin D for the Weight Loss Effect of Roux-en-Y Gastric Bypass Surgery in Obese Patients
- Author
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Bandstein, Marcus, Schultes, Bernd, Ernst, Barbara, Thurnheer, Martin, Schiöth, Helgi B., and Benedict, Christian
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- 2015
- Full Text
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3. An obesity-associated risk allele within the FTO gene affects human brain activity for areas important for emotion, impulse control and reward in response to food images
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Wiemerslage, Lyle, Nilsson, Emil K., Solstrand Dahlberg, Linda, Ence-Eriksson, Fia, Castillo, Sandra, Larsen, Anna L., Bylund, Simon B. A., Hogenkamp, Pleunie S., Olivo, Gaia, Bandstein, Marcus, Titova, Olga E., Larsson, Elna-Marie, Benedict, Christian, Brooks, Samantha J., Schiöth, Helgi B., and Foxe, John
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- 2016
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4. A pharmacogenetic risk score for the evaluation of major depression severity under treatment with antidepressants
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Kanders, Sofia H., Pisanu, Claudia, Bandstein, Marcus, Jonsson, Jörgen, Castelao, Enrique, Pistis, Giorgio, Gholam-Rezaee, Mehdi, Eap, Chin B., Preisig, Martin, Schiöth, Helgi B., and Mwinyi, Jessica
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Adult ,Male ,Pharmacogenomic Variants ,Pharmacology and Toxicology ,genetic risk score ,treatment with antidepressants ,Polymorphism, Single Nucleotide ,Severity of Illness Index ,Humans ,Prospective Studies ,Research Articles ,pharmacogenetics ,Aged ,Depressive Disorder, Major ,Middle Aged ,Farmakologi och toxikologi ,Antidepressive Agents ,Cytochrome P-450 CYP2C19 ,Treatment Outcome ,depression ,random forest ,Receptor, Serotonin, 5-HT1A ,Female ,Switzerland ,Research Article - Abstract
The severity of symptoms as well as efficacy of antidepressants in major depressive disorder (MDD) is modified by single nucleotide polymorphisms (SNPs) in different genes, which may contribute in an additive or synergistic fashion. We aimed to investigate depression severity in participants with MDD under treatment with antidepressants in relation to the combinatory effect of selected genetic variants combined using a genetic risk score (GRS). The sample included 150 MDD patients on regular AD therapy from the population‐based Swiss PsyCoLaus cohort. We investigated 44 SNPs previously associated with antidepressant response by ranking them with regard to their association to the Center for Epidemiologic Studies Short Depression Scale (CES‐D) score using random forest. The three top scoring SNPs (rs12248560, rs878567, rs17710780) were subsequently combined into an unweighted GRS, which was included in linear and logistic regression models using the CES‐D score, occurrence of a major depressive episode (MDE) during follow‐up and regular antidepressant treatment during the 6 months preceding follow‐up assessment as outcomes. The GRS was associated with MDE occurrence (p = .02) and ln CES‐D score (p = .001). The HTR1A rs878567 variant was associated with ln CES‐D after adjustment for demographic and clinical variables [p = .02, lower scores for minor allele (G) carriers]. Additionally, rs12248560 (CYP2C19) CC homozygotes showed a six‐fold higher likelihood of regular AD therapy at follow‐up compared to minor allele homozygotes [TT; ultrarapid metabolizers (p = .03)]. Our study suggests that the cumulative consideration of pharmacogenetic risk variants more reliably reflects the impact of the genetic background on depression severity than individual SNPs.
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- 2020
5. Hypermethylation-associated downregulation of microRNA-4456 in hypersexual disorder with putative influence on oxytocin signalling : A DNA methylation analysis of miRNA genes
- Author
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Chatzittofis, Andreas, Boström, Adrian E., Ciuculete, Diana-Maria, Flanagan, John N., Krattinger, Regina, Bandstein, Marcus, Mwinyi, Jessica, Kullak-Ublick, Gerd A., Öberg, Katarina Görts, Arver, Stefan, Schiöth, Helgi B., Jokinen, Jussi, University of Zurich, Boström, Adrian E, and Chatzittofis, Andreas [0000-0002-6635-9564]
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Male ,0301 basic medicine ,Cancer Research ,microRNA expression ,Methylome-wide ,Oxytocin ,MIR4456 ,0302 clinical medicine ,1306 Cancer Research ,DNA methylation ,Mental Disorders ,MicroRNA ,Middle Aged ,psychiatry ,030220 oncology & carcinogenesis ,Medical genetics ,Female ,epigenetic dysregulation ,Medical Genetics ,Research Paper ,Signal Transduction ,medicine.drug ,Adult ,medicine.medical_specialty ,hypersexual disorder ,Sexual Behavior ,Down-Regulation ,610 Medicine & health ,differential methylation ,Biology ,03 medical and health sciences ,Downregulation and upregulation ,gene target prediction ,microRNA ,oxytocin ,medicine ,1312 Molecular Biology ,Humans ,Epigenetics ,Gene ,Molecular Biology ,Aged ,Medicinsk genetik ,epigenetics ,MicroRNAs ,030104 developmental biology ,10199 Clinic for Clinical Pharmacology and Toxicology ,Cancer research ,Hypersexual disorder ,oxytocin signaling ,hsa-miR-4456 ,microRNA-4456 - Abstract
Hypersexual disorder (HD) was proposed as a diagnosis in the DSM-5 and the classification ?Compulsive Sexual Behavior Disorder? is now presented as an impulse-control disorder in ICD-11. HD incorporates several pathophysiological mechanisms; including impulsivity, compulsivity, sexual desire dysregulation and sexual addiction. No previous study investigated HD in a methylation analysis limited to microRNA (miRNA) associated CpG-sites. The genome wide methylation pattern was measured in whole blood from 60 subjects with HD and 33 healthy volunteers using the Illumina EPIC BeadChip. 8,852 miRNA associated CpG-sites were investigated in multiple linear regression analyses of methylation M-values to a binary independent variable of disease state (HD or healthy volunteer), adjusting for optimally determined covariates. Expression levels of candidate miRNAs were investigated in the same individuals for differential expression analysis. Candidate methylation loci were further studied for an association with alcohol dependence in an independent cohort of 107 subjects. Two CpG-sites were borderline significant in HD ? cg18222192 (MIR708)(p < 10E-05,p(FDR) = 5.81E-02) and cg01299774 (MIR4456)(p < 10E-06, p(FDR) = 5.81E-02). MIR4456 was significantly lower expressed in HD in both univariate (p < 0.0001) and multivariate (p < 0.05) analyses. Cg01299774 methylation levels were inversely correlated with expression levels of MIR4456 (p < 0.01) and were also differentially methylated in alcohol dependence (p = 0.026). Gene target prediction and pathway analysis revealed that MIR4456 putatively targets genes preferentially expressed in brain and that are involved in major neuronal molecular mechanisms thought to be relevant for HD, e.g., the oxytocin signalling pathway. In summary, our study implicates a potential contribution of MIR4456 in the pathophysiology of HD by putatively influencing oxytocin signalling.
- Published
- 2020
6. Hypermethylation-associated downregulation of microRNA-4456 in hypersexual disorder with putative influence on oxytocin signalling : A DNA methylation analysis of miRNA genes
- Author
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Boström, Adrian, Chatzittofis, Andreas, Ciuculete, Diana-Maria, Flanagan, John N., Krattinger, Regina, Bandstein, Marcus, Mwinyi, Jessica, Kullak-Ublick, Gerd A., Oberg, Katarina Gorts, Arver, Stefan, Schiöth, Helgi B., Jokinen, Jussi, Boström, Adrian, Chatzittofis, Andreas, Ciuculete, Diana-Maria, Flanagan, John N., Krattinger, Regina, Bandstein, Marcus, Mwinyi, Jessica, Kullak-Ublick, Gerd A., Oberg, Katarina Gorts, Arver, Stefan, Schiöth, Helgi B., and Jokinen, Jussi
- Abstract
Hypersexual disorder (HD) was proposed as a diagnosis in the DSM-5 and the classification ?Compulsive Sexual Behavior Disorder? is now presented as an impulse-control disorder in ICD-11. HD incorporates several pathophysiological mechanisms; including impulsivity, compulsivity, sexual desire dysregulation and sexual addiction. No previous study investigated HD in a methylation analysis limited to microRNA (miRNA) associated CpG-sites. The genome wide methylation pattern was measured in whole blood from 60 subjects with HD and 33 healthy volunteers using the Illumina EPIC BeadChip. 8,852 miRNA associated CpG-sites were investigated in multiple linear regression analyses of methylation M-values to a binary independent variable of disease state (HD or healthy volunteer), adjusting for optimally determined covariates. Expression levels of candidate miRNAs were investigated in the same individuals for differential expression analysis. Candidate methylation loci were further studied for an association with alcohol dependence in an independent cohort of 107 subjects. Two CpG-sites were borderline significant in HD ? cg18222192 (MIR708)(p < 10E-05,p(FDR) = 5.81E-02) and cg01299774 (MIR4456)(p < 10E-06, p(FDR) = 5.81E-02). MIR4456 was significantly lower expressed in HD in both univariate (p < 0.0001) and multivariate (p < 0.05) analyses. Cg01299774 methylation levels were inversely correlated with expression levels of MIR4456 (p < 0.01) and were also differentially methylated in alcohol dependence (p = 0.026). Gene target prediction and pathway analysis revealed that MIR4456 putatively targets genes preferentially expressed in brain and that are involved in major neuronal molecular mechanisms thought to be relevant for HD, e.g., the oxytocin signalling pathway. In summary, our study implicates a potential contribution of MIR4456 in the pathophysiology of HD by putatively influencing oxytocin signalling.
- Published
- 2020
- Full Text
- View/download PDF
7. Hypermethylation-associated downregulation of microRNA-4456 in hypersexual disorder with putative influence on oxytocin signalling: A DNA methylation analysis of miRNA genes
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Boström, Adrian E; https://orcid.org/0000-0001-8604-9638, Chatzittofis, Andreas; https://orcid.org/0000-0002-6635-9564, Ciuculete, Diana-Maria; https://orcid.org/0000-0001-6377-0270, Flanagan, John N; https://orcid.org/0000-0001-6957-756X, Krattinger, Regina, Bandstein, Marcus; https://orcid.org/0000-0002-7071-9067, Mwinyi, Jessica, Kullak-Ublick, Gerd A, Öberg, Katarina Görts, Arver, Stefan, Schiöth, Helgi B, Jokinen, Jussi, Boström, Adrian E; https://orcid.org/0000-0001-8604-9638, Chatzittofis, Andreas; https://orcid.org/0000-0002-6635-9564, Ciuculete, Diana-Maria; https://orcid.org/0000-0001-6377-0270, Flanagan, John N; https://orcid.org/0000-0001-6957-756X, Krattinger, Regina, Bandstein, Marcus; https://orcid.org/0000-0002-7071-9067, Mwinyi, Jessica, Kullak-Ublick, Gerd A, Öberg, Katarina Görts, Arver, Stefan, Schiöth, Helgi B, and Jokinen, Jussi
- Abstract
Hypersexual disorder (HD) was proposed as a diagnosis in the DSM-5 and the classification ‘Compulsive Sexual Behavior Disorder’ is now presented as an impulse-control disorder in ICD-11. HD incorporates several pathophysiological mechanisms; including impulsivity, compulsivity, sexual desire dysregulation and sexual addiction. No previous study investigated HD in a methylation analysis limited to microRNA (miRNA) associated CpG-sites. The genome wide methylation pattern was measured in whole blood from 60 subjects with HD and 33 healthy volunteers using the Illumina EPIC BeadChip. 8,852 miRNA associated CpG-sites were investigated in multiple linear regression analyses of methylation M-values to a binary independent variable of disease state (HD or healthy volunteer), adjusting for optimally determined covariates. Expression levels of candidate miRNAs were investigated in the same individuals for differential expression analysis. Candidate methylation loci were further studied for an association with alcohol dependence in an independent cohort of 107 subjects. Two CpG-sites were borderline significant in HD – cg18222192 (MIR708)(p < 10E-05,pFDR = 5.81E-02) and cg01299774 (MIR4456)(p < 10E-06, pFDR = 5.81E-02). MIR4456 was significantly lower expressed in HD in both univariate (p < 0.0001) and multivariate (p < 0.05) analyses. Cg01299774 methylation levels were inversely correlated with expression levels of MIR4456 (p < 0.01) and were also differentially methylated in alcohol dependence (p = 0.026). Gene target prediction and pathway analysis revealed that MIR4456 putatively targets genes preferentially expressed in brain and that are involved in major neuronal molecular mechanisms thought to be relevant for HD, e.g., the oxytocin signalling pathway. In summary, our study implicates a potential contribution of MIR4456 in the pathophysiology of HD by putatively influencing oxytocin signalling.
- Published
- 2020
8. A pharmacogenetic risk score for the evaluation of major depression severity under treatment with antidepressants
- Author
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Kanders, Sofia H., primary, Pisanu, Claudia, additional, Bandstein, Marcus, additional, Jonsson, Jörgen, additional, Castelao, Enrique, additional, Pistis, Giorgio, additional, Gholam‐Rezaee, Mehdi, additional, Eap, Chin B., additional, Preisig, Martin, additional, Schiöth, Helgi B., additional, and Mwinyi, Jessica, additional
- Published
- 2019
- Full Text
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9. Hypermethylation-associated downregulation of microRNA-4456 in hypersexual disorder with putative influence on oxytocin signalling: A DNA methylation analysis of miRNA genes
- Author
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Boström, Adrian E., primary, Chatzittofis, Andreas, additional, Ciuculete, Diana-Maria, additional, Flanagan, John N., additional, Krattinger, Regina, additional, Bandstein, Marcus, additional, Mwinyi, Jessica, additional, Kullak-Ublick, Gerd A., additional, Öberg, Katarina Görts, additional, Arver, Stefan, additional, Schiöth, Helgi B., additional, and Jokinen, Jussi, additional
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- 2019
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10. Hypermethylation-associated downregulation of microRNA-4456 in hypersexual disorder with putative influence on oxytocin signalling: A DNA methylation analysis of miRNA genes.
- Author
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Boström, Adrian E., Chatzittofis, Andreas, Ciuculete, Diana-Maria, Flanagan, John N., Krattinger, Regina, Bandstein, Marcus, Mwinyi, Jessica, Kullak-Ublick, Gerd A., Öberg, Katarina Görts, Arver, Stefan, Schiöth, Helgi B., and Jokinen, Jussi
- Abstract
Hypersexual disorder (HD) was proposed as a diagnosis in the DSM-5 and the classification 'Compulsive Sexual Behavior Disorder' is now presented as an impulse-control disorder in ICD-11. HD incorporates several pathophysiological mechanisms; including impulsivity, compulsivity, sexual desire dysregulation and sexual addiction. No previous study investigated HD in a methylation analysis limited to microRNA (miRNA) associated CpG-sites. The genome wide methylation pattern was measured in whole blood from 60 subjects with HD and 33 healthy volunteers using the Illumina EPIC BeadChip. 8,852 miRNA associated CpG-sites were investigated in multiple linear regression analyses of methylation M-values to a binary independent variable of disease state (HD or healthy volunteer), adjusting for optimally determined covariates. Expression levels of candidate miRNAs were investigated in the same individuals for differential expression analysis. Candidate methylation loci were further studied for an association with alcohol dependence in an independent cohort of 107 subjects. Two CpG-sites were borderline significant in HD – cg18222192 (MIR708)(p < 10E-05,p
FDR = 5.81E-02) and cg01299774 (MIR4456)(p < 10E-06, pFDR = 5.81E-02). MIR4456 was significantly lower expressed in HD in both univariate (p < 0.0001) and multivariate (p < 0.05) analyses. Cg01299774 methylation levels were inversely correlated with expression levels of MIR4456 (p < 0.01) and were also differentially methylated in alcohol dependence (p = 0.026). Gene target prediction and pathway analysis revealed that MIR4456 putatively targets genes preferentially expressed in brain and that are involved in major neuronal molecular mechanisms thought to be relevant for HD, e.g., the oxytocin signalling pathway. In summary, our study implicates a potential contribution of MIR4456 in the pathophysiology of HD by putatively influencing oxytocin signalling. [ABSTRACT FROM AUTHOR]- Published
- 2020
- Full Text
- View/download PDF
11. A methylome-wide mQTL analysis reveals associations of methylation sites with GAD1 and HDAC3 SNPs and a general psychiatric risk score
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Ciuculete, Diana-Maria, Boström, Adrian E., Voisin, Sarah, Philipps, H., Titova, Olga E., Bandstein, Marcus, Nikontovic, Lamia, Williams, Michael J., Mwinyi, Jessica, Schiöth, Helgi B., Ciuculete, Diana-Maria, Boström, Adrian E., Voisin, Sarah, Philipps, H., Titova, Olga E., Bandstein, Marcus, Nikontovic, Lamia, Williams, Michael J., Mwinyi, Jessica, and Schiöth, Helgi B.
- Abstract
Genome-wide association studies have identified a number of single-nucleotide polymorphisms (SNPs) that are associated with psychiatric diseases. Increasing body of evidence suggests a complex connection of SNPs and the transcriptional and epigenetic regulation of gene expression, which is poorly understood. In the current study, we investigated the interplay between genetic risk variants, shifts in methylation and mRNA levels in whole blood from 223 adolescents distinguished by a risk for developing psychiatric disorders. We analyzed 37 SNPs previously associated with psychiatric diseases in relation to genome-wide DNA methylation levels using linear models, with Bonferroni correction and adjusting for cell-type composition. Associations between DNA methylation, mRNA levels and psychiatric disease risk evaluated by the Development and Well-Being Assessment (DAWBA) score were identified by robust linear models, Pearson's correlations and binary regression models. We detected five SNPs (in HCRTR1, GAD1, HADC3 and FKBP5) that were associated with eight CpG sites, validating five of these SNP-CpG pairs. Three of these CpG sites, that is, cg01089319 (GAD1), cg01089249 (GAD1) and cg24137543 (DIAPH1), manifest in significant gene expression changes and overlap with active regulatory regions in chromatin states of brain tissues. Importantly, methylation levels at cg01089319 were associated with the DAWBA score in the discovery group. These results show how distinct SNPs linked with psychiatric diseases are associated with epigenetic shifts with relevance for gene expression. Our findings give a novel insight on how genetic variants may modulate risks for the development of psychiatric diseases.
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- 2017
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12. A DNA methylation site within the KLF13 gene is associated with orexigenic processes based on neural responses and ghrelin levels
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Wiemerslage, Lyle, Islam, R., van der Kamp, C, Cao, Hao, Olivo, Gaia, Ence-Eriksson, F, Castillo, S, Larsen, A L, Bandstein, Marcus, Dahlberg, L S, Perland, E, Gustavsson, V, Nilsson, J, Vogel, H, Schürmann, A, Larsson, Elna-Marie, Rask-Andersen, Mathias, Benedict, Christian, Schiöth, Helgi B., Wiemerslage, Lyle, Islam, R., van der Kamp, C, Cao, Hao, Olivo, Gaia, Ence-Eriksson, F, Castillo, S, Larsen, A L, Bandstein, Marcus, Dahlberg, L S, Perland, E, Gustavsson, V, Nilsson, J, Vogel, H, Schürmann, A, Larsson, Elna-Marie, Rask-Andersen, Mathias, Benedict, Christian, and Schiöth, Helgi B.
- Abstract
We investigated five methylation markers recently linked to body-mass index, for their role in the neuropathology of obesity. In neuroimaging experiments, our analysis involving 23 participants showed that methylation levels for the cg07814318 site, which lies within the KLF13 gene, correlated with brain activity in the claustrum, putamen, cingulate gyrus, and frontal gyri, some of which have been previously associated to food signaling, obesity, or reward. Methylation levels at cg07814318 also positively correlated with ghrelin levels. Moreover, expression of KLF13 was augmented in the brains of obese and starved mice. Our results suggest the cg07814318 site could be involved in orexigenic processes, and also implicate KLF13 in obesity. Our findings are the first to associate methylation levels in blood with brain activity in obesity-related regions, and further support previous findings between ghrelin, brain activity, and genetic differences.
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- 2017
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13. A genetic risk score is significantly associated with statin therapy response in the elderly population
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Ciuculete, Diana-Maria, Bandstein, Marcus, Benedict, Christian, Waeber, G., Vollenweider, P., Lind, Lars, Schiöth, Helgi B., Mwinyi, Jessica, Ciuculete, Diana-Maria, Bandstein, Marcus, Benedict, Christian, Waeber, G., Vollenweider, P., Lind, Lars, Schiöth, Helgi B., and Mwinyi, Jessica
- Abstract
The ability of statins to strongly reduce low-density lipoprotein cholesterol (LDL-C) varies interindividually and is partially influenced by genetic variants. Based on a comprehensive analysis of 23 single nucleotide polymorphisms (SNPs) known to be associated with pharmacokinetics and dynamics of statins, we developed a genetic risk score to study its impact on the therapy outcome in elderly individuals under at least 5 years statin therapy. The study was performed in a population-based cohort of 1016 elderly individuals, which comprised 168 statin users investigated at age 75 and 80. Using random forest models, the major variants influencing LDL-C levels were summarized in a weighted GRS (wGRS). The wGRS was tested with lipid and glucose outcomes and validated in an independent population-based cohort including 221 statin users. Four SNPs within the APOE cluster (rs7412, rs4420638), ABCC2 (rs2002042) and CELSR/SORT1/PSRC1 (rs646776), displayed a major impact on statin efficacy. The wGRS was significantly associated with lower LDL-C at age 75 and 80. This association was replicated displaying similar results. GRS analysis is a powerful tool to evaluate the additive effects of genetic variants on statin response and to estimate the magnitude of LDL-C reduction to a considerable extent in the older population.
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- 2017
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14. A genetic variant in proximity to the gene LYPLAL1 is associated with lower hunger feelings and increased weight loss following Roux-en Y gastric bypass surgery
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Bandstein, Marcus, Mwinyi, Jessica, Ernst, Barbara, Thurnheer, Martin, Schultes, Bernd, and Schiöth, Helgi
- Subjects
Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi ,nutritional and metabolic diseases ,Public Health, Global Health, Social Medicine and Epidemiology ,Medical Genetics ,Medicinsk genetik - Abstract
Objective: Bariatric surgery is the most efficient treatment of severe obesity. We investigated to what extent BMI- or waist-hip ratio (WHR)-related genetic variants are associated with excess BMI loss (EBMIL) two years after Roux-en-Y gastric bypass (RYGB) surgery, and elucidated the affected biological pathways. Methods: Two-hundred fifty-one obese patients (age: 4310.7, preoperative BMI: 45.16.1kg/m(2), 186 women) underwent RYGB surgery and were followed up after two years with regard to BMI. Patients were genotyped for 32 single-nucleotide polymorphisms (SNPs) that were investigated with regard to their impact on response to RYGB and preoperatively measured Three Factor Eating Questionnaire (TFEQ) scores. Results: Homozygous T carriers of the SNP rs4846567 in proximity to the Lysophospholipase-like 1 (LYPLAL1) gene showed a 7% higher EBMIL compared to wild-type and heterozygous carriers (p=0.031). TT-allele carriers showed furthermore lower scores for Hunger (74%, p
- Published
- 2016
15. The role of genetics in regulation of weight loss and food intake
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Bandstein, Marcus
- Subjects
LYPLAL1 ,food intake ,RYGB ,methylation ,FTO ,Medical Genetics ,TFEQ ,Genetic Risk Score ,Medicinsk genetik - Abstract
While obesity is a world leading health problem, the most efficient treatment option for severely obese patients is Roux-Y gastric bypass (RYGB) surgery. However, there are large inter-individual differences in weight loss after RYGB surgery. The reasons for this are not yet elucidated and the role of genetics in weight loss-regulation is still not fully understood. The main aim for this thesis was to investigate the effects of common obesity-associated genetic variants and their effect on weight loss and food intake. We examined if the weight loss two years following RYGB surgery depends on the FTO genotype, as well as pre-surgery vitamin D status. For FTO AA-carriers, the surgery resulted in a 3% per-allele increased excess BMI loss (EBMIL; P=0.02). When split by vitamin D baseline status, the EBMIL of vitamin D deficient patients carrying AA exceeded that of vitamin D deficient patients carrying TT by 14% (P=0.03). No such genotypic differences were found in patients without pre-surgery vitamin D deficiency. As the influence of individual single nucleotide polymorphisms may be small, we identified a novel method to combine SNPs into a genetic risk score (GRS). Using the random forest model, SNPs with high impact on weight loss after RYGB surgery were filtered out. An up to 11% lower EBMIL with higher risk score was estimated for the GRS model (p=0.026) composed of seven BMI-associated SNPs (closest genes: MC4R, TMEM160, PTBP2, NUDT3, TFAP2B, ZNF608 and MAP2K5). Pre-surgical hunger feelings were found to be associated with EBMIL and the SNP rs4846567. Before surgery, patients filled out the Three Factor Eating Questionnaire and were genotyped for known BMI and waist-hip ratio (WHR) associated SNPs. Patients with the lowest hunger scores had up to 32% greater EBMIL compared to the highest scoring patients (P=0.002). TT-allele carriers of rs4846567 showed a 58% lower hunger feelings. TT- carriers also showed a 51% decrease in disinhibition, but no significant impact on cognitive restraint was observed. Due to the association of eating behaviour and weight loss, acute effects on DNA methylation in response to a food intake intervention of a standardized meal were also investigated. After food intake, 1832 CpG sites were differentially methylated compared to the baseline after multiple testing correction. When adjusted for white blood cell fractions, 541 CpG sites remained. This may be interpreted as that the immune system is playing an active role in the response to food intake and highlights the dynamic nature of DNA-methylation. These findings will contribute to a better care for morbidly obese patients. Post-surgical treatment may be optimized so that patients with a less favourable genetic profile may receive additional support for weight loss and weight management. This may be considered as a step in the transition towards personalized medicine.
- Published
- 2016
16. Resting-State Bra in and the FTO Obesity Risk Allele : Default Mode, Sensorimotor, and Salience Network Connectivity Underlying Different Somatosensory Integration and Reward Processing between Genotypes
- Author
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Olivo, Gaia, Wiemerslage, Lyle, Nilsson, Emil K., Dahlberg, Linda Solstrand, Larsen, Anna L., Bucaro, Marcela Olaya, Gustafsson, Veronica P., Titova, Olga E., Bandstein, Marcus, Larsson, Elna-Marie, Benedict, Christian, Brooks, Samantha J., Schioth, Helgi B., Olivo, Gaia, Wiemerslage, Lyle, Nilsson, Emil K., Dahlberg, Linda Solstrand, Larsen, Anna L., Bucaro, Marcela Olaya, Gustafsson, Veronica P., Titova, Olga E., Bandstein, Marcus, Larsson, Elna-Marie, Benedict, Christian, Brooks, Samantha J., and Schioth, Helgi B.
- Abstract
Single-nucleotide polymorphisms (SNPs) of the fat mass and obesity associated (FTO) gene are linked to obesity, but how these SNPs influence resting-state neural activation is unknown. Few brain-imaging studies have investigated the influence of obesity-related SNPs on neural activity, and no study has investigated resting-state connectivity patterns. We tested connectivity within three, main resting-state networks: default mode (DMN), sensorimotor (SMN), and salience network (SN) in 30 male participants, grouped based on genotype for the rs9939609 FTO SNP, as well as punishment and reward sensitivity measured by the Behavioral Inhibition (BIS) and Behavioral Activation System (BAS) questionnaires. Because obesity is associated with anomalies in both systems, we calculated a BIS/BAS ratio (BBr) accounting for features of both scores. A prominence of BIS over BAS (higher BBr) resulted in increased connectivity in frontal and paralimbic regions. These alterations were more evident in the obesity-associated AA genotype, where a high BBr was also associated with increased SN connectivity in dopaminergic circuitries, and in a subnetwork involved in somatosensory integration regarding food. Participants with AA genotype and high BBr, compared to corresponding participants in the TT genotype, also showed greater DMN connectivity in regions involved in the processing of food cues, and in the SMN for regions involved in visceral perception and reward-based learning. These findings suggest that neural connectivity patterns influence the sensitivity toward punishment and reward more closely in the AA carriers, predisposing them to developing obesity. Our work explains a complex interaction between genetics, neural patterns, and behavioral measures in determining the risk for obesity and may help develop individually-tailored strategies for obesity prevention., De två första författarna delar förstaförfattarskapet.
- Published
- 2016
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17. A genetic risk score is associated with weight loss following Roux-Y gastric bypass surgery
- Author
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Bandstein, Marcus, Voisin, Sarah, Nilsson, Emil, Schultes, Bernd, Ernst, Barbara, Benedict, Christian, Mwinyi, Jessica, Schiöth, Helgi, Bandstein, Marcus, Voisin, Sarah, Nilsson, Emil, Schultes, Bernd, Ernst, Barbara, Benedict, Christian, Mwinyi, Jessica, and Schiöth, Helgi
- Abstract
Currently, Roux-en Y gastric bypass (RYGB) is the most efficient therapy for severe obesity. Weight loss after surgery is, however, highly variable and genetically influenced. Genome-wide association studies have identified several single nucleotide polymorphisms (SNP) associated with body mass index (BMI) and waist-hip ratio (WHR). We aimed to identify two genetic risk scores (GRS) composed of weighted BMI and WHR-associated SNPs to estimate their impact on excess BMI loss (EBMIL) after RYGB surgery. Two hundred and thirty-eight obese patients (BMI 45.1 +/- 6.2 kg/m(2), 74 % women), who underwent RYGB, were genotyped for 35 BMI and WHR-associated SNPs and were followed up after 2 years. SNPs with high impact on post-surgical weight loss were filtered out using a random forest model. The filtered SNPs were combined into a GRS and analyzed in a linear regression model. An up to 11 % lower EBMIL with higher risk score was estimated for two GRS models (P = 0.026 resp. P = 0.021) composed of seven BMI-associated SNPs (closest genes: MC4R, TMEM160, PTBP2, NUDT3, TFAP2B, ZNF608, MAP2K5, GNPDA2, and MTCH2) and of three WHR-associated SNPs (closest genes: HOXC13, LYPLAL1, and DNM3-PIGC). Patients within the lowest GRS quartile had higher EBMIL compared to patients within the other three quartiles in both models. We identified two GRSs composed of BMI and WHR-associated SNPs with significant impact on weight loss after RYGB surgery using random forest analysis as a SNP selection tool. The GRS may be useful to pre-surgically evaluate the risks for patients undergoing RYGB surgery.
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- 2016
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18. Postprandial alterations in whole-blood DNA methylation are mediated by changes in white blood cell composition
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Rask-Andersen, Mathias, Bringeland, Nathalie, Nilsson, Emil K., Bandstein, Marcus, Búcaro, Marcela Olaya, Vogel, Heike, Schuermann, Annette, Hogenkamp, Pleunie S., Benedict, Christian, Schiöth, Helgi B., Rask-Andersen, Mathias, Bringeland, Nathalie, Nilsson, Emil K., Bandstein, Marcus, Búcaro, Marcela Olaya, Vogel, Heike, Schuermann, Annette, Hogenkamp, Pleunie S., Benedict, Christian, and Schiöth, Helgi B.
- Abstract
Background: DNA methylation is an essential nuclear process associated with genomic functions such as transcription factor binding and the regulation of gene expression. DNA methylation patterns can also serve as potential biomarkers for disease progression and response to therapy. However, the full dynamics of DNA methylation across daily physiologic events have not been fully elucidated. Objective: We sought to study how ingesting a standardized meal acutely affects peripheral blood DNA methylation. Design: We performed an observational study in healthy men (n = 26) on DNA methylation and gene expression in whole blood before and 160 min after the ingestion of a standardized meal. Cytosine-phosphate-guanine (CpG) methylation was assayed on the HumanMethylation450k microarray, and gene expression was measured with the Human Gene 2.1 ST Array. Results: Differential methylation after food intake was detected in 13% of the analyzed probes (63,207 CpG probes) at a 5% false discovery rate (FDR). This effect was driven by changes in leukocyte fractions as estimated from comparisons against methylation datasets generated from sorted leukocytes. When methylation values were adjusted for estimated leukocyte fractions, 541 probes were observed to be altered in the postprandial state (5% FDR). Conclusions: Apparent alterations in DNA methylation 160 min after meal ingestion mainly reflect changes in the estimated leukocyte population in whole blood. These results have major methodologic implications for genome-wide methylation studies because they highlight the strong underlying effects of changes in leukocyte fractions on CpG methylation patterns as well as the potential importance of meal-standardized sampling procedures for future investigations when alterations in white blood cell fractions are unavailable.
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- 2016
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19. Major difference in DNA methylation in blood between fasted and postprandial state; before and 160 min after meal
- Author
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Rask-Andersen, Mathias, Bringeland, Nathalie, Nilsson, Emil, Bandstein, Marcus, Olaya Búcaro, Marcela, Vogel, Heike, Schürmann, Annette, Hogenkamp, Pleunie, Benedict, Christian, Schiöth, Helgi, Rask-Andersen, Mathias, Bringeland, Nathalie, Nilsson, Emil, Bandstein, Marcus, Olaya Búcaro, Marcela, Vogel, Heike, Schürmann, Annette, Hogenkamp, Pleunie, Benedict, Christian, and Schiöth, Helgi
- Published
- 2016
20. Postprandial alterations in whole-blood DNA methylation are mediated by changes in white blood cell composition ,
- Author
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Rask-Andersen, Mathias, primary, Bringeland, Nathalie, additional, Nilsson, Emil K, additional, Bandstein, Marcus, additional, Olaya Búcaro, Marcela, additional, Vogel, Heike, additional, Schürmann, Annette, additional, Hogenkamp, Pleunie S, additional, Benedict, Christian, additional, and Schiöth, Helgi B, additional
- Published
- 2016
- Full Text
- View/download PDF
21. A genetic variant in proximity to the gene LYPLAL1 is associated with lower hunger feelings and increased weight loss following Roux-en-Y gastric bypass surgery
- Author
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Bandstein, Marcus, primary, Mwinyi, Jessica, additional, Ernst, Barbara, additional, Thurnheer, Martin, additional, Schultes, Bernd, additional, and Schiöth, Helgi B., additional
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- 2016
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- View/download PDF
22. An obesity-associated risk allele within theFTOgene affects human brain activity for areas important for emotion, impulse control and reward in response to food images
- Author
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Wiemerslage, Lyle, primary, Nilsson, Emil K., additional, Solstrand Dahlberg, Linda, additional, Ence-Eriksson, Fia, additional, Castillo, Sandra, additional, Larsen, Anna L., additional, Bylund, Simon B. A., additional, Hogenkamp, Pleunie S., additional, Olivo, Gaia, additional, Bandstein, Marcus, additional, Titova, Olga E., additional, Larsson, Elna-Marie, additional, Benedict, Christian, additional, Brooks, Samantha J., additional, and Schiöth, Helgi B., additional
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- 2016
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23. Resting-State Brain and the FTO Obesity Risk Allele: Default Mode, Sensorimotor, and Salience Network Connectivity Underlying Different Somatosensory Integration and Reward Processing between Genotypes
- Author
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Olivo, Gaia, primary, Wiemerslage, Lyle, additional, Nilsson, Emil K., additional, Solstrand Dahlberg, Linda, additional, Larsen, Anna L., additional, Olaya Búcaro, Marcela, additional, Gustafsson, Veronica P., additional, Titova, Olga E., additional, Bandstein, Marcus, additional, Larsson, Elna-Marie, additional, Benedict, Christian, additional, Brooks, Samantha J., additional, and Schiöth, Helgi B., additional
- Published
- 2016
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24. A pharmacogenetic risk score for the evaluation of major depression severity under treatment with antidepressants.
- Author
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Kanders SH, Pisanu C, Bandstein M, Jonsson J, Castelao E, Pistis G, Gholam-Rezaee M, Eap CB, Preisig M, Schiöth HB, and Mwinyi J
- Subjects
- Adult, Aged, Depressive Disorder, Major genetics, Female, Humans, Male, Middle Aged, Pharmacogenomic Variants, Prospective Studies, Severity of Illness Index, Switzerland, Treatment Outcome, Antidepressive Agents therapeutic use, Cytochrome P-450 CYP2C19 genetics, Depressive Disorder, Major drug therapy, Polymorphism, Single Nucleotide, Receptor, Serotonin, 5-HT1A genetics
- Abstract
The severity of symptoms as well as efficacy of antidepressants in major depressive disorder (MDD) is modified by single nucleotide polymorphisms (SNPs) in different genes, which may contribute in an additive or synergistic fashion. We aimed to investigate depression severity in participants with MDD under treatment with antidepressants in relation to the combinatory effect of selected genetic variants combined using a genetic risk score (GRS). The sample included 150 MDD patients on regular AD therapy from the population-based Swiss PsyCoLaus cohort. We investigated 44 SNPs previously associated with antidepressant response by ranking them with regard to their association to the Center for Epidemiologic Studies Short Depression Scale (CES-D) score using random forest. The three top scoring SNPs (rs12248560, rs878567, rs17710780) were subsequently combined into an unweighted GRS, which was included in linear and logistic regression models using the CES-D score, occurrence of a major depressive episode (MDE) during follow-up and regular antidepressant treatment during the 6 months preceding follow-up assessment as outcomes. The GRS was associated with MDE occurrence (p = .02) and ln CES-D score (p = .001). The HTR1A rs878567 variant was associated with ln CES-D after adjustment for demographic and clinical variables [p = .02, lower scores for minor allele (G) carriers]. Additionally, rs12248560 (CYP2C19) CC homozygotes showed a six-fold higher likelihood of regular AD therapy at follow-up compared to minor allele homozygotes [TT; ultrarapid metabolizers (p = .03)]. Our study suggests that the cumulative consideration of pharmacogenetic risk variants more reliably reflects the impact of the genetic background on depression severity than individual SNPs., (© 2019 The Authors. Drug Development Research published by Wiley Periodicals, Inc.)
- Published
- 2020
- Full Text
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