Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
21364883
TITLE
Deep sequencing of the Nicastrin gene in pooled DNA, the identification of genetic variants that affect risk of Alzheimer's disease.
ABSTRACT
Nicastrin is an obligatory component of the γ-secretase; the enzyme complex that leads to the production of Aβ fragments critically central to the pathogenesis of Alzheimer's disease (AD). Analyses of the effects of common variation in this gene on risk for late onset AD have been inconclusive. We investigated the effect of rare variation in the coding regions of the Nicastrin gene in a cohort of AD patients and matched controls using an innovative pooling approach and next generation sequencing. Five SNPs were identified and validated by individual genotyping from 311 cases and 360 controls. Association analysis identified a non-synonymous rare SNP (N417Y) with a statistically higher frequency in cases compared to controls in the Greek population (OR 3.994, CI 1.105-14.439, p = 0.035). This finding warrants further investigation in a larger cohort and adds weight to the hypothesis that rare variation explains some of genetic heritability still to be identified in Alzheimer's disease.
DATE PUBLISHED
2011
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2010/11/02
accepted 2011/01/27
epublish 2011/02/25
entrez 2011/03/03 06:00
pubmed 2011/03/03 06:00
medline 2011/09/02 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Lupton MK Lupton Michelle K MK MRC Centre for Neurodegeneration Research, Institute of Psychiatry, King's College London, London, United Kingdom.
Proitsi P Proitsi Petroula P
Danillidou M Danillidou Makrina M
Tsolaki M Tsolaki Magda M
Hamilton G Hamilton Gillian G
Wroe R Wroe Richard R
Pritchard M Pritchard Megan M
Lord K Lord Kathryn K
Martin BM Martin Belinda M BM
Kloszewska I Kloszewska Iwona I
Soininen H Soininen Hilkka H
Mecocci P Mecocci Patrizia P
Vellas B Vellas Bruno B
Harold D Harold Denise D
Hollingworth P Hollingworth Paul P
Lovestone S Lovestone Simon S
Powell JF Powell John F JF
INVESTIGATORS
JOURNAL
VOLUME: 6
ISSUE: 2
TITLE: PloS one
ISOABBREVIATION: PLoS ONE
YEAR: 2011
MONTH:
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1932-6203
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: PLoS One
COUNTRY: United States
ISSNLINKING: 1932-6203
NLMUNIQUEID: 101285081
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Aged
Aged, 80 and over
Alzheimer Disease genetics
Amyloid Precursor Protein Secretases genetics
Case-Control Studies genetics
DNA analysis
Gene Frequency analysis
Genetic Predisposition to Disease analysis
Genetic Variation physiology
High-Throughput Nucleotide Sequencing methods
Humans methods
Membrane Glycoproteins genetics
Meta-Analysis as Topic genetics
Middle Aged genetics
Polymorphism, Single Nucleotide physiology
Risk Factors physiology
Specimen Handling methods
Validation Studies as Topic methods
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Membrane Glycoproteins
0 nicastrin protein
9007-49-2 DNA
EC 3.4.- Amyloid Precursor Protein Secretases
OTHER ID's
OTHERID SOURCE
PMC3045431 NLM
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