Journal
AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
Volume 135B, Issue 1, Pages 24-32Publisher
WILEY
DOI: 10.1002/ajmg.b.30114
Keywords
Alzheimer's Disease; age at onset; rate of decline; genome screen; linkage
Categories
Funding
- NIA NIH HHS [U24 AG021886] Funding Source: Medline
- NIMH NIH HHS [U01 MH46281, U01 MH46290, U01 MH46373] Funding Source: Medline
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We performed an affected sib-pair (ASP) linkage analysis to test for the effects of age at onset (AAO), rate of decline (ROD), and Apolipoprotein E (APOE) genotype on linkage to late-onset Alzheimer's disease (AD) in a sample comprising 428 sib-pairs. We observed linkage of mean AAO to chromosome 21 in the whole sample (max LOD = 2.57). This came entirely from the NIMH sample (max LOD=3.62), and was strongest in pairs with high mean AAO (> 80). A similar effect was observed on chromosome 2q in the NIMH sample (max LOD=2.73); this region was not typed in the IADC/UK sample. Suggestive evidence was observed in the combined sample of linkage of AAO difference to chromosome 19q (max LOD=2.33) in the vicinity of APOE and 12p (max LOD=2.22), with linkage strongest in sib-pairs with similar AAO. Mean ROD showed suggestive evidence of linkage to chromosome 9q in the whole sample (max LOD=2.29), with the effect strongest in the NIMH sample (max LOD=3.58), and in pairs with high mean ROD. Additional suggestive evidence was also observed in the NIMH sample with AAO difference on chromosome 6p (max LOD=2.44) and 15p (max LOD=1.87), with linkage strongest in pairs with similar AAO, and in the UK sample with mean ROD on chromosome 1p (max LOD=2.73, linkage strongest in pairs with high mean ROD). We also observed suggestive evidence of increased identical by descent (IBD) in APOE EA homozygotes on chromosome 1 (max LOD=3.08) and chromosome 9 (max LOD=3.34). The previously reported genome-wide linkage of AD to chromosome 10 was not influenced by any of the covariates studied. (c) 2005 Wiley-Liss, Inc.
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