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Article ; Online: Genetics and Epigenetics in Personalized Nutrition: Evidence, Expectations, and Experiences.

Holzapfel, Christina / Waldenberger, Melanie / Lorkowski, Stefan / Daniel, Hannelore

2022 Volume 66, Issue 17, Page(s) e2200077

Abstract: With the presentation of the blueprint of the first human genome in 2001 and the advent of technologies for high-throughput genetic analysis, personalized nutrition (PN) becomes a new scientific field and the first commercial offerings of genotype-based ... ...

Abstract	With the presentation of the blueprint of the first human genome in 2001 and the advent of technologies for high-throughput genetic analysis, personalized nutrition (PN) becomes a new scientific field and the first commercial offerings of genotype-based nutrition advice emerge at the same time. Here, the state of evidence for the effect of genetic and epigenetic factors in the development of obesity, the metabolic syndrome, and resulting illnesses such as non-insulin-dependent diabetes mellitus and cardiovascular diseases is summarized. This study also critically value the concepts of PN that are built around the new genetic avenue from both the academic and a commercial perspective and their effectiveness in causing sustained changes in diet, lifestyle, and for improving health. Despite almost 20 years of research and commercial direct-to-consumer offerings, evidence for the success of gene-based dietary recommendations is still generally lacking. This calls for new concepts of future PN solutions that incorporate more phenotypic measures and provide a panel of instruments (e.g., self- and bio-monitoring tools, feedback systems, algorithms based on artificial intelligence) that increases compliance based on the individual´s physical and social environment and value system.
MeSH term(s)	Artificial Intelligence ; Diet ; Epigenesis, Genetic ; Humans ; Motivation ; Nutritional Status
Language	English
Publishing date	2022-07-10
Publishing country	Germany
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2160372-8
ISSN	1613-4133 ; 1613-4125
ISSN (online)	1613-4133
ISSN	1613-4125
DOI	10.1002/mnfr.202200077
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Article: Genetics and Epigenetics in Personalized Nutrition: Evidence, Expectations, and Experiences

Holzapfel, Christina / Waldenberger, Melanie / Lorkowski, Stefan / Daniel, Hannelore

Molecular nutrition & food research. 2022 Sept., v. 66, no. 17

2022

Abstract: With the presentation of the blueprint of the first human genome in 2001 and the advent of technologies for high‐throughput genetic analysis, personalized nutrition (PN) becomes a new scientific field and the first commercial offerings of genotype‐based ... ...

Institution	the Working Group “Personalized Nutrition” of the German Nutrition SocietyInstitute for Nutritional Medicine, School of Medicine, Technical University of Munich, 81675, Munich, Germany
Abstract	With the presentation of the blueprint of the first human genome in 2001 and the advent of technologies for high‐throughput genetic analysis, personalized nutrition (PN) becomes a new scientific field and the first commercial offerings of genotype‐based nutrition advice emerge at the same time. Here, the state of evidence for the effect of genetic and epigenetic factors in the development of obesity, the metabolic syndrome, and resulting illnesses such as non‐insulin‐dependent diabetes mellitus and cardiovascular diseases is summarized. This study also critically value the concepts of PN that are built around the new genetic avenue from both the academic and a commercial perspective and their effectiveness in causing sustained changes in diet, lifestyle, and for improving health. Despite almost 20 years of research and commercial direct‐to‐consumer offerings, evidence for the success of gene‐based dietary recommendations is still generally lacking. This calls for new concepts of future PN solutions that incorporate more phenotypic measures and provide a panel of instruments (e.g., self‐ and bio‐monitoring tools, feedback systems, algorithms based on artificial intelligence) that increases compliance based on the individual´s physical and social environment and value system.
Keywords	artificial intelligence ; compliance ; diet ; environmental monitoring ; epigenetics ; food research ; genetic analysis ; genome ; humans ; lifestyle ; metabolic syndrome ; noninsulin-dependent diabetes mellitus ; obesity ; phenotype ; social environment
Language	English
Dates of publication	2022-09
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	REVIEW
ZDB-ID	2160372-8
ISSN	1613-4133 ; 1613-4125
ISSN (online)	1613-4133
ISSN	1613-4125
DOI	10.1002/mnfr.202200077
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Article: Cluster Analysis Statistical Spectroscopy for the Identification of Metabolites in

Heinzmann, Silke S / Waldenberger, Melanie / Peters, Annette / Schmitt-Kopplin, Philippe

Metabolites

2022 Volume 12, Issue 10

Abstract: Metabolite identification in non-targeted NMR-based metabolomics remains a challenge. While many peaks of frequently occurring metabolites are assigned, there is a high number of unknowns in high-resolution NMR spectra, hampering biological conclusions ... ...

Abstract	Metabolite identification in non-targeted NMR-based metabolomics remains a challenge. While many peaks of frequently occurring metabolites are assigned, there is a high number of unknowns in high-resolution NMR spectra, hampering biological conclusions for biomarker analysis. Here, we use a cluster analysis approach to guide peak assignment via statistical correlations, which gives important information on possible structural and/or biological correlations from the NMR spectrum. Unknown peaks that cluster in close proximity to known peaks form hypotheses for their metabolite identities, thus, facilitating metabolite annotation. Subsequently, metabolite identification based on a database search, 2D NMR analysis and standard spiking is performed, whereas without a hypothesis, a full structural elucidation approach would be required. The approach allows a higher identification yield in NMR spectra, especially once pathway-related subclusters are identified.
Language	English
Publishing date	2022-10-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662251-8
ISSN	2218-1989
ISSN	2218-1989
DOI	10.3390/metabo12100992
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Article ; Online: DNA methylation in human lipid metabolism and related diseases.

Mittelstraß, Kirstin / Waldenberger, Melanie

Current opinion in lipidology

2018 Volume 29, Issue 2, Page(s) 116–124

Abstract: Purpose of review: It is becoming increasingly evident that epigenetic mechanisms, particularly DNA methylation, play a role in the regulation of blood lipid levels and lipid metabolism-linked phenotypes and diseases.: Recent findings: Recent genome- ... ...

Abstract	Purpose of review: It is becoming increasingly evident that epigenetic mechanisms, particularly DNA methylation, play a role in the regulation of blood lipid levels and lipid metabolism-linked phenotypes and diseases. Recent findings: Recent genome-wide methylation and candidate gene studies of blood lipids have highlighted several robustly replicated methylation markers across different ethnicities. Furthermore, many of these lipid-related CpG sites associated with blood lipids are also linked to lipid-related phenotypes and diseases. Integrating epigenome-wide association studies (EWAS) data with other layers of molecular data such as genetics or the transcriptome, accompanied by relevant statistical methods (e.g. Mendelian randomization), provides evidence for causal relationships. Recent data suggest that epigenetic changes can be consequences rather than causes of dyslipidemia. There is sparse information on many lipid classes and disorders of lipid metabolism, and also on the interplay of DNA methylation with other epigenetic layers such as histone modifications and regulatory RNAs. Summary: The current review provides a literature overview of epigenetic modifications in lipid metabolism and other lipid-related phenotypes and diseases focusing on EWAS of DNA methylation from January 2016 to September 2017. Recent studies strongly support the importance of epigenetic modifications, such as DNA methylation, in lipid metabolism and related diseases for relevant biological insights, reliable biomarkers, and even future therapeutics.
MeSH term(s)	Animals ; Computational Biology ; CpG Islands/genetics ; DNA Methylation ; Disease/genetics ; Humans ; Lipid Metabolism/genetics
Language	English
Publishing date	2018-03-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1045394-5
ISSN	1473-6535 ; 0957-9672
ISSN (online)	1473-6535
ISSN	0957-9672
DOI	10.1097/MOL.0000000000000491
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Article: Usual dietary intake and change in DNA methylation over years: EWAS in KORA FF4 and KORA fit.

Hellbach, Fabian / Freuer, Dennis / Meisinger, Christa / Peters, Annette / Winkelmann, Juliane / Costeira, Ricardo / Hauner, Hans / Baumeister, Sebastian-Edgar / Bell, Jordana T / Waldenberger, Melanie / Linseisen, Jakob

Frontiers in nutrition

2024 Volume 10, Page(s) 1295078

Abstract: Introduction: Changes in DNA methylation can increase or suppress the expression of health-relevant genes. We investigated for the first time the relationship between habitual food consumption and changes in DNA methylation.: Methods: The German KORA ...

Abstract	Introduction: Changes in DNA methylation can increase or suppress the expression of health-relevant genes. We investigated for the first time the relationship between habitual food consumption and changes in DNA methylation. Methods: The German KORA FF4 and KORA Fit studies were used to study the change in methylation over a median follow-up of 4 years. Only subjects participating in both surveys and with available dietary and methylation data were included in the analysis (n = 465). DNA methylation was measured using the Infinium MethylationEPIC BeadChip (Illumina), resulting in 735,527 shared CpGs across both studies. Generalized estimating equation models with an interaction term of exposure and time point were used to analyze the association of 34 food groups, folic acid, and two dietary patterns with changes in DNA methylation over time. Results: The results were corrected for genomic inflation. Significant interaction terms indicate different effects between both time points. We observed only a few significant associations between food intake and change in DNA methylation, except for cream and spirit consumption. The annotated genes include CLN3, PROM1, DLEU7, TLL2, and UGT1A10. Discussion: We identified weak associations between food consumption and DNA methylation change. The differential results for cream and spirits, both consumed in low quantities, require replication in independent studies.
Language	English
Publishing date	2024-01-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2776676-7
ISSN	2296-861X
ISSN	2296-861X
DOI	10.3389/fnut.2023.1295078
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Article ; Online: Common electrocardiogram measures are not associated with telomere length.

von Falkenhausen, Aenne S / Freudling, Rebecca / Waldenberger, Melanie / Gieger, Christian / Peters, Annette / Müller-Nurasyid, Martina / Kääb, Stefan / Sinner, Moritz F

Aging

2022 Volume 14, Issue 14, Page(s) 5620–5627

Abstract: Aims: Aging is accompanied by telomere shortening. Increased telomere shortening is considered a marker of premature aging. Cardiac aging results in the development of cardiac pathologies. Electrocardiogram (ECG) measures reflect cardiac excitation, ... ...

Abstract	Aims: Aging is accompanied by telomere shortening. Increased telomere shortening is considered a marker of premature aging. Cardiac aging results in the development of cardiac pathologies. Electrocardiogram (ECG) measures reflect cardiac excitation, conduction, and repolarization. ECG measures also prolong with aging and are associated with cardiac pathologies including atrial fibrillation. As premature prolongation of ECG measures is observed, we hypothesized that such prolongation may be associated with telomere length. Methods and results: We studied the large, community-based KORA F4 Study. Of 3,080 participants enrolled between 2006 and 2007 with detailed information on demographic, anthropometric, clinical, and ECG characteristics, 2,575 presented with available data on leukocyte telomere length. Telomere length was determined by real-time quantitative PCR and expressed relative to a single copy gene. We fitted multivariable adjusted linear regression models to associate the ECG measures RR-interval, PR-interval, QRS-duration, and heart rate corrected QTc with telomere length. In our cohort, the mean age was 54.9±12.9 years and 46.6% were men. Increased age was associated with shorter telomere length (p<0.01), and men had shorter telomere length than women (p<0.05). In unadjusted models, heart rate (p=0.023), PR-interval (p<0.01), and QTc-interval (p<0.01) were significantly associated with shorter telomere length. However, no significant associations remained after accounting for age, sex, and covariates. Conclusions: ECG measures are age-dependent, but not associated with shortened telomere length as a marker of biological aging. Further research is warranted to clarify if shortened telomeres are associated with clinical cardiac pathologies including atrial fibrillation.
MeSH term(s)	Aged ; Aging/genetics ; Atrial Fibrillation/diagnosis ; Atrial Fibrillation/genetics ; Electrocardiography ; Female ; Humans ; Leukocytes ; Male ; Telomere/genetics ; Telomere Shortening
Language	English
Publishing date	2022-07-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1945-4589
ISSN (online)	1945-4589
DOI	10.18632/aging.204149
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Article ; Online: Derivation and validation of an epigenetic frailty risk score in population-based cohorts of older adults.

Li, Xiangwei / Delerue, Thomas / Schöttker, Ben / Holleczek, Bernd / Grill, Eva / Peters, Annette / Waldenberger, Melanie / Thorand, Barbara / Brenner, Hermann

Nature communications

2022 Volume 13, Issue 1, Page(s) 5269

Abstract: DNA methylation (DNAm) patterns in peripheral blood have been shown to be associated with aging related health outcomes. We perform an epigenome-wide screening to identify CpGs related to frailty, defined by a frailty index (FI), in a large population- ... ...

Abstract	DNA methylation (DNAm) patterns in peripheral blood have been shown to be associated with aging related health outcomes. We perform an epigenome-wide screening to identify CpGs related to frailty, defined by a frailty index (FI), in a large population-based cohort of older adults from Germany, the ESTHER study. Sixty-five CpGs are identified as frailty related methylation loci. Using LASSO regression, 20 CpGs are selected to derive a DNAm based algorithm for predicting frailty, the epigenetic frailty risk score (eFRS). The eFRS exhibits strong associations with frailty at baseline and after up to five-years of follow-up independently of established frailty risk factors. These associations are confirmed in another independent population-based cohort study, the KORA-Age study, conducted in older adults. In conclusion, we identify 65 CpGs as frailty-related loci, of which 20 CpGs are used to calculate the eFRS with predictive performance for frailty over long-term follow-up.
MeSH term(s)	Aged ; Cohort Studies ; Epigenesis, Genetic ; Epigenomics ; Frailty/genetics ; Humans ; Risk Factors
Language	English
Publishing date	2022-09-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-32893-x
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Article ; Online: Epigenome-wide association study of dietary fatty acid intake.

Lange de Luna, Julia / Nounu, Aayah / Neumeyer, Sonja / Sinke, Lucy / Wilson, Rory / Hellbach, Fabian / Matías-García, Pamela R / Delerue, Thomas / Winkelmann, Juliane / Peters, Annette / Thorand, Barbara / Beekman, Marian / Heijmans, Bastiaan T / Slagboom, Eline / Gieger, Christian / Linseisen, Jakob / Waldenberger, Melanie

Clinical epigenetics

2024 Volume 16, Issue 1, Page(s) 29

Abstract: Background: Dietary intake of n-3 polyunsaturated fatty acids (PUFA) may have a protective effect on the development of cardiovascular diseases, diabetes, depression and cancer, while a high intake of n-6 PUFA was often reported to be associated with ... ...

Abstract	Background: Dietary intake of n-3 polyunsaturated fatty acids (PUFA) may have a protective effect on the development of cardiovascular diseases, diabetes, depression and cancer, while a high intake of n-6 PUFA was often reported to be associated with inflammation-related traits. The effect of PUFAs on health outcomes might be mediated by DNA methylation (DNAm). The aim of our study is to identify the impact of PUFA intake on DNAm in the Cooperative Health Research in the Region of Augsburg (KORA) FF4 cohort and the Leiden Longevity Study (LLS). Results: DNA methylation levels were measured in whole blood from the population-based KORA FF4 study (N = 1354) and LLS (N = 448), using the Illumina MethylationEPIC BeadChip and Illumina HumanMethylation450 array, respectively. We assessed associations between DNAm and intake of eight and four PUFAs in KORA and LLS, respectively. Where possible, results were meta-analyzed. Below the Bonferroni correction threshold (p < 7.17 × 10 Conclusions: Our study identified three CpG sites associated with PUFA intake. The mechanisms of these sites remain largely unexplored, highlighting the novelty of our findings. Further research is essential to understand the links between CpG site methylation and PUFA outcomes.
MeSH term(s)	Humans ; Epigenome ; DNA Methylation ; Fatty Acids, Omega-3 ; Fatty Acids ; Docosahexaenoic Acids ; Repressor Proteins
Chemical Substances	Fatty Acids, Omega-3 ; Fatty Acids ; Docosahexaenoic Acids (25167-62-8) ; CDCA7L protein, human ; Repressor Proteins
Language	English
Publishing date	2024-02-16
Publishing country	Germany
Document type	Meta-Analysis ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553921-8
ISSN	1868-7083 ; 1868-7075
ISSN (online)	1868-7083
ISSN	1868-7075
DOI	10.1186/s13148-024-01643-9
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Article ; Online: Associations between medium- and long-term exposure to air temperature and epigenetic age acceleration.

Ni, Wenli / Nikolaou, Nikolaos / Ward-Caviness, Cavin K / Breitner, Susanne / Wolf, Kathrin / Zhang, Siqi / Wilson, Rory / Waldenberger, Melanie / Peters, Annette / Schneider, Alexandra

Environment international

2023 Volume 178, Page(s) 108109

Abstract: Climate change poses a serious threat to human health worldwide, while aging populations increase. However, no study has ever investigated the effects of air temperature on epigenetic age acceleration. This study involved 1,725 and 1,877 participants ... ...

Abstract	Climate change poses a serious threat to human health worldwide, while aging populations increase. However, no study has ever investigated the effects of air temperature on epigenetic age acceleration. This study involved 1,725 and 1,877 participants from the population-based KORA F4 (2006-2008) and follow-up FF4 (2013-2014) studies, respectively, conducted in Augsburg, Germany. The difference between epigenetic age and chronological age was referred to as epigenetic age acceleration and reflected by Horvath's epigenetic age acceleration (HorvathAA), Hannum's epigenetic age acceleration (HannumAA), PhenoAge acceleration (PhenoAA), GrimAge acceleration (GrimAA), and Epigenetic Skin and Blood Age acceleration (SkinBloodAA). Daily air temperature was estimated using hybrid spatiotemporal regression-based models. To explore the medium- and long-term effects of air temperature modeled in time and space on epigenetic age acceleration, we applied generalized estimating equations (GEE) with distributed lag non-linear models, and GEE, respectively. We found that high temperature exposure based on the 8-week moving average air temperature (97.5th percentile of temperature compared to median temperature) was associated with increased HorvathAA, HannumAA, GrimAA, and SkinBloodAA: 1.83 (95% CI: 0.29-3.37), 11.71 (95% CI: 8.91-14.50), 2.26 (95% CI: 1.03-3.50), and 5.02 (95% CI: 3.42-6.63) years, respectively. Additionally, we found consistent results with high temperature exposure based on the 4-week moving average air temperature was associated with increased HannumAA, GrimAA, and SkinBloodAA: 9.18 (95% CI: 6.60-11.76), 1.78 (95% CI: 0.66-2.90), and 4.07 (95% CI: 2.56-5.57) years, respectively. For the spatial variation in annual average temperature, a 1 °C increase was associated with an increase in all five measures of epigenetic age acceleration (HorvathAA: 0.41 [95% CI: 0.24-0.57], HannumAA: 2.24 [95% CI: 1.95-2.53], PhenoAA: 0.32 [95% CI: 0.05-0.60], GrimAA: 0.24 [95%: 0.11-0.37], and SkinBloodAA: 1.17 [95% CI: 1.00-1.35] years). In conclusion, our results provide first evidence that medium- and long-term exposures to high air temperature affect increases in epigenetic age acceleration.
MeSH term(s)	Humans ; Infant ; Air Pollution/analysis ; Temperature ; Particulate Matter/analysis ; Aging/genetics ; Epigenesis, Genetic ; DNA Methylation
Chemical Substances	Particulate Matter
Language	English
Publishing date	2023-07-23
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	554791-x
ISSN	1873-6750 ; 0160-4120
ISSN (online)	1873-6750
ISSN	0160-4120
DOI	10.1016/j.envint.2023.108109
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Article ; Online: Epigenetic Association Analyses and Risk Prediction of RLS.

Harrer, Philip / Mirza-Schreiber, Nazanin / Mandel, Vanessa / Roeber, Sigrun / Stefani, Ambra / Naher, Shamsun / Wagner, Matias / Gieger, Christian / Waldenberger, Melanie / Peters, Annette / Högl, Birgit / Herms, Jochen / Schormair, Barbara / Zhao, Chen / Winkelmann, Juliane / Oexle, Konrad

Movement disorders : official journal of the Movement Disorder Society

2023 Volume 38, Issue 8, Page(s) 1410–1418

Abstract: Background: As opposed to other neurobehavioral disorders, epigenetic analyses and biomarkers are largely missing in the case of idiopathic restless legs syndrome (RLS).: Objectives: Our aims were to develop a biomarker for RLS based on DNA ... ...

Abstract	Background: As opposed to other neurobehavioral disorders, epigenetic analyses and biomarkers are largely missing in the case of idiopathic restless legs syndrome (RLS). Objectives: Our aims were to develop a biomarker for RLS based on DNA methylation in blood and to examine DNA methylation in brain tissues for dissecting RLS pathophysiology. Methods: Methylation of blood DNA from three independent cohorts (n = 2283) and post-mortem brain DNA from two cohorts (n = 61) was assessed by Infinium EPIC 850 K BeadChip. Epigenome-wide association study (EWAS) results of individual cohorts were combined by random-effect meta-analysis. A three-stage selection procedure (discovery, n = 884; testing, n = 520; validation, n = 879) established an epigenetic risk score including 30 CpG sites. Epigenetic age was assessed by Horvath's multi-tissue clock and Shireby's cortical clock. Results: EWAS meta-analysis revealed 149 CpG sites linked to 136 genes (P < 0.05 after Bonferroni correction) in blood and 23 CpG linked to 18 genes in brain (false discovery rate [FDR] < 5%). Gene-set analyses of blood EWAS results suggested enrichments in brain tissue types and in subunits of the kainate-selective glutamate receptor complex. Individual candidate genes of the brain EWAS could be assigned to neurodevelopmental or metabolic traits. The blood epigenetic risk score achieved an area under the curve (AUC) of 0.70 (0.67-0.73) in the validation set, comparable to analogous scores in other neurobehavioral disorders. A significant difference in biological age in blood or brain of RLS patients was not detectable. Conclusions: DNA methylation supports the notion of altered neurodevelopment in RLS. Epigenetic risk scores are reliably associated with RLS but require even higher accuracy to be useful as biomarkers. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
MeSH term(s)	Humans ; Epigenesis, Genetic/genetics ; Restless Legs Syndrome/genetics ; DNA Methylation/genetics ; DNA ; Genome-Wide Association Study/methods ; Biomarkers ; CpG Islands/genetics
Chemical Substances	DNA (9007-49-2) ; Biomarkers
Language	English
Publishing date	2023-05-22
Publishing country	United States
Document type	Meta-Analysis ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	607633-6
ISSN	1531-8257 ; 0885-3185
ISSN (online)	1531-8257
ISSN	0885-3185
DOI	10.1002/mds.29440
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