Full genome screen for Alzheimer disease: Stage II analysis

Myers, Amanda, Wavrant De-Vrieze, Fabienne, Holmans, Peter Alan ORCID: https://orcid.org/0000-0003-0870-9412, Hamshere, Marian Lindsay ORCID: https://orcid.org/0000-0002-8990-0958, Crook, Richard, Compton, Danielle, Marshall, Helen, Meyer, David, Shears, Shantia, Booth, Jeremy, Ramic, Dzanan, Knowles, Heather, Morris, John C., Williams, Nigel Melville ORCID: https://orcid.org/0000-0003-1177-6931, Norton, Nadine, Abraham, Richard, Kehoe, Pat, Williams, Hywel, Rudrasingham, Varuni, Rice, Frances ORCID: https://orcid.org/0000-0002-9484-1729, Giles, Peter ORCID: https://orcid.org/0000-0003-3143-6854, Tunstall, Nigel, Jones, Lesley ORCID: https://orcid.org/0000-0002-3007-4612, Lovestone, Simon, Williams, Julie ORCID: https://orcid.org/0000-0002-4069-0259, Owen, Michael John ORCID: https://orcid.org/0000-0003-4798-0862, Hardy, John and Goate, Alison 2002. Full genome screen for Alzheimer disease: Stage II analysis. American Journal Of Medical Genetics Part A 114 (2) , pp. 235-244. 10.1002/ajmg.10183

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Abstract

We performed a two-stage genome screen to search for novel risk factors for late-onset Alzheimer disease (AD). The first stage involved genotyping 292 affected sibling pairs using 237 markers spaced at approximately 20 cM intervals throughout the genome. In the second stage, we genotyped 451 affected sibling pairs (ASPs) with an additional 91 markers, in the 16 regions where the multipoint LOD score was greater than 1 in stage I. Ten regions maintained LOD scores in excess of 1 in stage II, on chromosomes 1 (peak B), 5, 6, 9 (peaks A and B), 10, 12, 19, 21, and X. Our strongest evidence for linkage was on chromosome 10, where we obtained a peak multipoint LOD score (MLS) of 3.9. The linked region on chromosome 10 spans approximately 44 cM from D10S1426 (59 cM) to D10S2327 (103 cM). To narrow this region, we tested for linkage disequilibrium with several of the stage II microsatellite markers. Of the seven markers we tested in family-based and case control samples, the only nominally positive association we found was with the 167 bp allele of marker D10S1217 (chi-square=7.11, P=0.045, df=1).

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Neuroscience and Mental Health Research Institute (NMHRI) Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects:	R Medicine > R Medicine (General)
ISSN:	0148-7299
Last Modified:	04 Mar 2023 03:02
URI:	https://orca.cardiff.ac.uk/id/eprint/82502

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