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01-07-2009 | Original Article

Extended tracts of homozygosity identify novel candidate genes associated with late-onset Alzheimer’s disease

Authors: M. A. Nalls, R. J. Guerreiro, J. Simon-Sanchez, J. T. Bras, B. J. Traynor, J. R. Gibbs, L. Launer, J. Hardy, A. B. Singleton

Published in: Neurogenetics | Issue 3/2009

Abstract

Large tracts of extended homozygosity are more prevalent in outbred populations than previously thought. With the advent of high-density genotyping platforms, regions of extended homozygosity can be accurately located allowing for the identification of rare recessive risk variants contributing to disease. We compared measures of extended homozygosity (greater than 1 Mb in length) in a population of 837 late-onset Alzheimer’s disease (LOAD) cases and 550 controls. In our analyses, we identify one homozygous region on chromosome 8 that is significantly associated with LOAD after adjusting for multiple testing. This region contains seven genes from which the most biologically plausible candidates are STAR, EIF4EBP1, and ADRB3. We also compared the total numbers of homozygous runs and the total length of these runs between cases and controls, showing a suggestive difference in these measures (p-values 0.052–0.062). This research suggests a recessive component to the etiology of LOAD.

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Title: Extended tracts of homozygosity identify novel candidate genes associated with late-onset Alzheimer’s disease
Authors: M. A. Nalls
R. J. Guerreiro
J. Simon-Sanchez
J. T. Bras
B. J. Traynor
J. R. Gibbs
L. Launer
J. Hardy
A. B. Singleton
Publication date: 01-07-2009
Publisher: Springer-Verlag
Published in: Neurogenetics / Issue 3/2009
Print ISSN: 1364-6745
Electronic ISSN: 1364-6753
DOI: https://doi.org/10.1007/s10048-009-0182-4

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Extended tracts of homozygosity identify novel candidate genes associated with late-onset Alzheimer’s disease

Abstract

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Abstract

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