No association or linkage between an intronic polymorphism of presenilin-1 and sporadic or late-onset familial Alzheimer disease

• Published in: Genetic epidemiology Vol. 14; no. 3; pp. 307 - 315
• Main Authors: Scott, W.K., Yamaoka, L.H., Locke, P.A., Rosi, B.L., Gaskell, P.C., Saunders, A.M., Conneally, P.M., Small, G.W., Farrer, L.A., Growdon, J.H., Roses, A.D., Pericak-Vance, M.A., Haines, J.L.
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 1997; Wiley-Liss
• Subjects: Age of Onset; Aged; Alzheimer Disease - epidemiology; Alzheimer Disease - genetics; APOE; Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; dementia; Female; Gene Frequency; genetics; Genotype; Humans; Introns; linkage analysis; Lod Score; Male; Medical sciences; Membrane Proteins - genetics; Middle Aged; Neurology; Polymorphism, Genetic; Presenilin-1; PSEN1; Regression Analysis; Software; Human; Nervous system diseases; Linkage; Alzheimer disease; Family study; Presenilin; Cerebral disorder; Association; Gene frequency; Gene; Central nervous system disease; Risk factor; Degenerative disease; Polymorphism
• ISSN: 0741-0395; 1098-2272
• DOI: 10.1002/(SICI)1098-2272(1997)14:3<307::AID-GEPI8>3.0.CO;2-1

Recent reports have shown an association between an intronic polymorphism of the presenilin‐1 (PSEN1) gene and late‐onset (age at onset > 65) familial and sporadic (no family history) Alzheimer disease (AD). The reported association was independent of the effect of the only previously identified gene associated with late‐onset AD, APOE. Blood samples were obtained from members of 122 multiplex AD families, 42 unrelated cases of AD with positive family histories of dementia, 456 sporadic cases of AD, and 317 controls of similar ages at examination to the cases. These samples were genotyped for an intronic polymorphism of the PSEN1 gene, located 3′ to exon 8, and the data analyzed for evidence of association or linkage. The samples were also genotyped for APOE and the data analyzed to see if the association or linkage changed when controlling for APOE genotype. There was no statistically significant increase (at α = .01) in allele 1 (199 bp) or genotype 1/1 in the sporadic AD cases, or in a random sample of one affected from each multiplex family, compared to controls. When examining the effect of the PSEN1 polymorphism while controlling for APOE genotype, APOE genotype was strongly associated with AD, but the PSEN1 polymorphism genotype was not. Model‐trait dependent (lod score) and independent (SimIBD) methods detected no evidence of linkage between PSEN1 and AD. In this independent dataset, the previously reported association between the intronic PSEN1 polymorphism and AD cannot be confirmed, and the conclusion that PSEN1 is a major susceptibility gene for late‐onset AD is not supported. Genet. Epidemiol. 14:307–315,1997. © 1997 Wiley‐Liss, Inc.