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Article: The Human Brainome: changes in expression of VGF, SPECC1L, HLA-DRA and RANBP3L act with APOE E4 to alter risk for late onset Alzheimer's disease.

Branciamore, Sergio / Gogoshin, Grigoriy / Rodin, Andrei S / Myers, Amanda J

Research square

2023

Abstract: While there are currently over 40 replicated genes with mapped risk alleles for Late Onset Alzheimer's disease (LOAD), ... ...

Abstract	While there are currently over 40 replicated genes with mapped risk alleles for Late Onset Alzheimer's disease (LOAD), the
Language	English
Publishing date	2023-12-14
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-3678057/v1
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Article ; Online: AD gene 3-D: moving past single layer genetic information to map novel loci involved in Alzheimer's disease.

Myers, Amanda J

Journal of Alzheimer's disease : JAD

2012 Volume 33 Suppl 1, Page(s) S15–22

Abstract: Over the past 5 years, there has been considerable advancement in the genetics of Alzheimer's disease. This review will provide an overview of the current state of the field for analysis of genetic variation and Alzheimer's disease. Highlighted in this ... ...

Abstract	Over the past 5 years, there has been considerable advancement in the genetics of Alzheimer's disease. This review will provide an overview of the current state of the field for analysis of genetic variation and Alzheimer's disease. Highlighted in this review will be the results from some of the more conventional approaches, including linkage and association studies, as well as an overview of an alternate approach: eQTL analysis. The emphasis will be on taking genomics to the next level by applying additional datasets to truly create maps of a 3-dimensional Alzheimer's genome by including the downstream effects of risk variation.
MeSH term(s)	Alzheimer Disease/genetics ; Genetic Association Studies/methods ; Genetic Linkage ; Genetic Loci ; Genetic Predisposition to Disease ; Genetic Variation ; Humans
Language	English
Publishing date	2012-06-03
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-2012-129013
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Zs.A 6084: Show issues

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Article ; Online: The age of the "ome": genome, transcriptome and proteome data set collection and analysis.

Myers, Amanda J

Brain research bulletin

2011 Volume 88, Issue 4, Page(s) 294–301

Abstract: The current state of human genetic studies is both a marvel and a morass. A marvel in that with the completion of the human genome sequence, projects that used to take years now take months or weeks; however, this creates a wealth of data concomitant to ... ...

Abstract	The current state of human genetic studies is both a marvel and a morass. A marvel in that with the completion of the human genome sequence, projects that used to take years now take months or weeks; however, this creates a wealth of data concomitant to a black hole of meaning. In terms of the well used analogy: the human genome sequence is a library in an ancient language with no Rosetta stone. Researchers have readily exploited the human genome map and thousands of candidate gene studies for a multitude of diseases have been performed. However, many of those studies have found that the variants associated with disease risk are not obvious coding changes. The question now becomes: what do these associations mean? One approach to the downstream mapping of associations is to use additional information to map which variant might truly be causative of risk and what that risk variant is doing. This review will summarize the current state of both data set collection and analysis for the understanding of DNA variants and their downstream effects on transcripts and proteins. This article is part of a Special Issue entitled 'Transcriptome'.
MeSH term(s)	Brain ; Chromosome Mapping ; Gene Expression Profiling/methods ; Gene Expression Profiling/trends ; Genome ; Genomics/methods ; Genomics/trends ; Humans ; Proteome ; Quantitative Trait Loci/genetics ; Transcriptome
Chemical Substances	Proteome
Language	English
Publishing date	2011-11-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	197620-5
ISSN	1873-2747 ; 0361-9230
ISSN (online)	1873-2747
ISSN	0361-9230
DOI	10.1016/j.brainresbull.2011.11.015
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Zs.A 1243: Show issues

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Article ; Online: APOE: a risk factor for multiple disorders.

Myers, Amanda J / Nemeroff, Charles B

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry

2012 Volume 20, Issue 7, Page(s) 545–548

MeSH term(s)	Aging/genetics ; Aging/psychology ; Alzheimer Disease/genetics ; Alzheimer Disease/psychology ; Apolipoproteins E/genetics ; Cognition Disorders/genetics ; Cognition Disorders/psychology ; Humans ; Risk Factors
Chemical Substances	Apolipoproteins E
Language	English
Publishing date	2012-05-22
Publishing country	England
Document type	Editorial ; Introductory Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	1278145-9
ISSN	1545-7214 ; 1064-7481
ISSN (online)	1545-7214
ISSN	1064-7481
DOI	10.1097/JGP.0b013e318259b9a5
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Zs.A 4443: Show issues

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Article ; Online: What does heritability of Alzheimer's disease represent?

Baker, Emily / Leonenko, Ganna / Schmidt, Karl Michael / Hill, Matthew / Myers, Amanda J / Shoai, Maryam / de Rojas, Itziar / Tesi, Niccoló / Holstege, Henne / van der Flier, Wiesje M / Pijnenburg, Yolande A L / Ruiz, Agustin / Hardy, John / van der Lee, Sven / Escott-Price, Valentina

PloS one

2023 Volume 18, Issue 4, Page(s) e0281440

Abstract: Introduction: Both late-onset Alzheimer's disease (AD) and ageing have a strong genetic component. In each case, many associated variants have been discovered, but how much missing heritability remains to be discovered is debated. Variability in the ... ...

Abstract	Introduction: Both late-onset Alzheimer's disease (AD) and ageing have a strong genetic component. In each case, many associated variants have been discovered, but how much missing heritability remains to be discovered is debated. Variability in the estimation of SNP-based heritability could explain the differences in reported heritability. Methods: We compute heritability in five large independent cohorts (N = 7,396, 1,566, 803, 12,528 and 3,963) to determine whether a consensus for the AD heritability estimate can be reached. These cohorts vary by sample size, age of cases and controls and phenotype definition. We compute heritability a) for all SNPs, b) excluding APOE region, c) excluding both APOE and genome-wide association study hit regions, and d) SNPs overlapping a microglia gene-set. Results: SNP-based heritability of late onset Alzheimer's disease is between 38 and 66% when age and genetic disease architecture are correctly accounted for. The heritability estimates decrease by 12% [SD = 8%] on average when the APOE region is excluded and an additional 1% [SD = 3%] when genome-wide significant regions were removed. A microglia gene-set explains 69-84% of our estimates of SNP-based heritability using only 3% of total SNPs in all cohorts. Conclusion: The heritability of neurodegenerative disorders cannot be represented as a single number, because it is dependent on the ages of cases and controls. Genome-wide association studies pick up a large proportion of total AD heritability when age and genetic architecture are correctly accounted for. Around 13% of SNP-based heritability can be explained by known genetic loci and the remaining heritability likely resides around microglial related genes.
MeSH term(s)	Humans ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Alzheimer Disease/genetics ; Genetic Loci ; Polymorphism, Single Nucleotide ; Apolipoproteins E/genetics
Chemical Substances	Apolipoproteins E
Language	English
Publishing date	2023-04-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0281440
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Article ; Online: Polygenic risk score analysis of pathologically confirmed Alzheimer disease.

Escott-Price, Valentina / Myers, Amanda J / Huentelman, Matt / Hardy, John

Annals of neurology

2017 Volume 82, Issue 2, Page(s) 311–314

Abstract: Previous estimates of the utility of polygenic risk score analysis for the prediction of Alzheimer disease have given area under the curve (AUC) estimates of <80%. However, these have been based on the genetic analysis of clinical case-control series. ... ...

Abstract	Previous estimates of the utility of polygenic risk score analysis for the prediction of Alzheimer disease have given area under the curve (AUC) estimates of <80%. However, these have been based on the genetic analysis of clinical case-control series. Here, we apply the same analytic approaches to a pathological case-control series and show a predictive AUC of 84%. We suggest that this analysis has clinical utility and that there is limited room for further improvement using genetic data. Ann Neurol 2017;82:311-314.
MeSH term(s)	Alzheimer Disease/diagnosis ; Alzheimer Disease/genetics ; Alzheimer Disease/pathology ; Area Under Curve ; Genetic Predisposition to Disease/genetics ; Genome-Wide Association Study ; Humans ; Models, Genetic ; Multifactorial Inheritance ; Polymorphism, Single Nucleotide/genetics ; Risk Assessment/methods
Language	English
Publishing date	2017-08-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	80362-5
ISSN	1531-8249 ; 0364-5134
ISSN (online)	1531-8249
ISSN	0364-5134
DOI	10.1002/ana.24999
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Zs.A 1370: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 478: Show issues

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Article ; Online: Disposal of fetal tissue following elective abortion: what women think.

Myers, Amanda J / Lohr, Patricia A / Pfeffer, Naomi

The journal of family planning and reproductive health care

2015 Volume 41, Issue 2, Page(s) 84–89

Abstract: Background and methodology: UK regulations on managing fetal tissue after pregnancy loss, including abortion, are underscored by the concept of 'sensitive disposal'. This involves offering women burial or cremation and, when disposal is by the health ... ...

Abstract	Background and methodology: UK regulations on managing fetal tissue after pregnancy loss, including abortion, are underscored by the concept of 'sensitive disposal'. This involves offering women burial or cremation and, when disposal is by the health care provider, separating fetal tissue from other clinical waste before incineration. We interviewed 23 women who had undergone one or more abortions about their understanding, attitudes and experiences of fetal tissue disposal and 'sensitive disposal'. Transcripts were analysed for representative themes. Results: Prior to the abortion, most participants did not give consideration to disposal methods because their focus was on ending the pregnancy. Appropriate disposal by health professionals was assumed but some women undergoing early medical abortion reported anxiety about how to manage disposal at home. The term 'sensitive disposal' was unfamiliar to most respondents. Participants generally favoured separation of fetal tissue from other clinical waste and approved of incineration as a means of destruction. Ceremonial disposal was approved of following the loss of a wanted pregnancy but not following elective abortion. Most wanted the opportunity to access information about disposal but did not favour being asked or required to make decisions about disposal. Discussion and conclusions: Knowledge about the management of fetal tissue after abortion or the concept of 'sensitive disposal' was limited among the women we interviewed. Current guidelines appear discordant with the views of women terminating an unwanted pregnancy. Further research is needed to better inform policy on this issue.
MeSH term(s)	Adolescent ; Adult ; Ambulatory Care Facilities/ethics ; Attitude to Health ; Female ; Fetus ; Humans ; Medical Waste Disposal/methods ; Middle Aged ; Pregnancy ; Qualitative Research ; United Kingdom
Chemical Substances	Medical Waste Disposal
Language	English
Publishing date	2015-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2113221-5
ISSN	2045-2098 ; 1471-1893
ISSN (online)	2045-2098
ISSN	1471-1893
DOI	10.1136/jfprhc-2013-100849
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Article ; Online: Retraction: 24-Hour Rhythms of DNA Methylation and Their Relation with Rhythms of RNA Expression in the Human Dorsolateral Prefrontal Cortex.

Lim, Andrew S P / Srivastava, Gyan P / Yu, Lei / Chibnik, Lori B / Xu, Jishu / Buchman, Aron S / Schneider, Julie A / Myers, Amanda J / Bennett, David A / De Jager, Philip L

PLoS genetics

2021 Volume 17, Issue 11, Page(s) e1009895

Language	English
Publishing date	2021-11-04
Publishing country	United States
Document type	Retraction of Publication
ZDB-ID	2186725-2
ISSN	1553-7404 ; 1553-7390
ISSN (online)	1553-7404
ISSN	1553-7390
DOI	10.1371/journal.pgen.1009895
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Article ; Online: Genetic analysis suggests high misassignment rates in clinical Alzheimer's cases and controls.

Escott-Price, Valentina / Baker, Emily / Shoai, Maryam / Leonenko, Ganna / Myers, Amanda J / Huentelman, Matt / Hardy, John

Neurobiology of aging

2019 Volume 77, Page(s) 178–182

Abstract: Genetic case-control association studies are often based on clinically ascertained cases and population or convenience controls. It is known that some of the controls will contain cases, as they are usually not screened for the disease of interest. ... ...

Abstract	Genetic case-control association studies are often based on clinically ascertained cases and population or convenience controls. It is known that some of the controls will contain cases, as they are usually not screened for the disease of interest. However, even clinically assessed cases and controls can be misassigned. For Alzheimer's disease (AD), it is important to know the accuracy of the clinical assignment. The predictive accuracy of AD risk by polygenic risk score analysis has been reported in both clinical and pathologically confirmed cohorts. The genetic risk prediction can provide additional insights to inform classification of subjects to case and control sets at a preclinical stage. In this study, we take a mathematical approach and aim to assess the importance of a genetic component for the assignment of subjects to AD-positive and -negative groups, and provide an estimate of misassignment rates (MARs) in AD case/control cohorts accounting for genetic prediction modeling results. The derived formulae provide a tool to estimate MARs in any sample. This approach can also provide an estimate of the maximal and minimal MARs and therefore could be useful for statistical power estimation at the study design stage. We illustrate this approach in 2 independent clinical cohorts and estimate misdiagnosis rate up to 36% in controls unscreened for the APOE genotype, and up to 29% when E3 homozygous subjects are used as controls in clinical studies.
MeSH term(s)	Aged ; Aged, 80 and over ; Alzheimer Disease/diagnosis ; Alzheimer Disease/genetics ; Apolipoproteins E/genetics ; Case-Control Studies ; Cohort Studies ; Diagnostic Errors/statistics & numerical data ; Female ; Genetic Association Studies ; Genotype ; Humans ; Male ; Risk
Chemical Substances	Apolipoproteins E
Language	English
Publishing date	2019-01-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	604505-4
ISSN	1558-1497 ; 0197-4580
ISSN (online)	1558-1497
ISSN	0197-4580
DOI	10.1016/j.neurobiolaging.2018.12.002
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Zs.A 1685: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 10: Show issues

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Article ; Online: Natural antisense transcripts.

Khorkova, Olga / Myers, Amanda J / Hsiao, Jane / Wahlestedt, Claes

Human molecular genetics

2014 Volume 23, Issue R1, Page(s) R54–63

Abstract: Recent years have seen the increasing understanding of the crucial role of RNA in the functioning of the eukaryotic genome. These discoveries, fueled by the achievements of the FANTOM, and later GENCODE and ENCODE consortia, led to the recognition of the ...

Abstract	Recent years have seen the increasing understanding of the crucial role of RNA in the functioning of the eukaryotic genome. These discoveries, fueled by the achievements of the FANTOM, and later GENCODE and ENCODE consortia, led to the recognition of the important regulatory roles of natural antisense transcripts (NATs) arising from what was previously thought to be 'junk DNA'. Roughly defined as non-coding regulatory RNA transcribed from the opposite strand of a coding gene locus, NATs are proving to be a heterogeneous group with high potential for therapeutic application. Here, we attempt to summarize the rapidly growing knowledge about this important non-coding RNA subclass.
MeSH term(s)	Gene Expression ; Gene Targeting ; Genome ; Humans ; RNA, Antisense/genetics ; RNA, Antisense/therapeutic use ; RNA, Untranslated/genetics ; Transcription, Genetic
Chemical Substances	RNA, Antisense ; RNA, Untranslated
Language	English
Publishing date	2014-05-16
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	1108742-0
ISSN	1460-2083 ; 0964-6906
ISSN (online)	1460-2083
ISSN	0964-6906
DOI	10.1093/hmg/ddu207
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Zs.A 3469: Show issues

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