Covariate analysis of late-onset Alzheimer disease refines the chromosome 12 locus

X. Liang, N. Schnetz-Boutaud, S. J. Kenealy, L. Jiang, J. Bartlett, B. Lynch, P. C. Gaskell, H. Gwirtsman, L. McFarland, M. L. Bembe, P. Bronson, John Gilbert, Eden R Martin, Margaret A Pericak-Vance, J. L. Haines

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Alzheimer disease (AD) is a progressive neurodegenerative disorder of later life with a complex etiology and a strong genetic component. Several genomic screens have suggested that a region between chromosome 12p13 and 12q22 contains at least one additional locus underlying the susceptibility of AD. However, localization of this locus has been difficult. We performed a 5 cM microsatellite marker screen across 74 cM on chromosome 12 with 15 markers in 585 multiplex families consisting of 994 affected sibpairs and 213 other affected relative pairs. Analyses across the entire data set did not reveal significant evidence of linkage. However, suggestive linkage was observed in several subsets. In the 91 families where no affected individuals carry an ApoE ε4 allele, an HLOD score of 1.55 was generated at D12S1042. We further examined the linkage data considering the proposed linkages to chromosome 9 (D9S741) and chromosome 10 (α-catenin gene). There was a modest (P = 0.20) increase in the LOD score for D12S368 (MLOD = 1.70) when using the D9S741 LOD scores as a covariate and a highly significant (P <; 0.001) increase in the MLOD score (4.19) for D12S1701 in autopsy-confirmed families (n = 228) when using α-catenin LOD scores as a covariate. In both cases, families with no evidence of linkage to D9S741 or α-catenin demonstrated most of the evidence of linkage to chromosome 12, suggesting locus heterogeneity. Taken together, our data suggest that the 16 cM region between D12S1042 and D12S368 should be the subject of further detailed genomic efforts for the disease.

Original languageEnglish
Pages (from-to)280-285
Number of pages6
JournalMolecular Psychiatry
Volume11
Issue number3
DOIs
StatePublished - Mar 1 2006
Externally publishedYes

Fingerprint

Catenins
Chromosomes, Human, Pair 12
Alzheimer Disease
Chromosomes, Human, Pair 10
Chromosomes, Human, Pair 9
Information Storage and Retrieval
Apolipoproteins E
Neurodegenerative Diseases
Microsatellite Repeats
Autopsy
Chromosomes
Alleles
Genes

Keywords

  • Alzheimer disease
  • Covariate analysis
  • Genetics
  • Genome screen
  • Linkage

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health

Cite this

Liang, X., Schnetz-Boutaud, N., Kenealy, S. J., Jiang, L., Bartlett, J., Lynch, B., ... Haines, J. L. (2006). Covariate analysis of late-onset Alzheimer disease refines the chromosome 12 locus. Molecular Psychiatry, 11(3), 280-285. https://doi.org/10.1038/sj.mp.4001766

Covariate analysis of late-onset Alzheimer disease refines the chromosome 12 locus. / Liang, X.; Schnetz-Boutaud, N.; Kenealy, S. J.; Jiang, L.; Bartlett, J.; Lynch, B.; Gaskell, P. C.; Gwirtsman, H.; McFarland, L.; Bembe, M. L.; Bronson, P.; Gilbert, John; Martin, Eden R; Pericak-Vance, Margaret A; Haines, J. L.

In: Molecular Psychiatry, Vol. 11, No. 3, 01.03.2006, p. 280-285.

Research output: Contribution to journalArticle

Liang, X, Schnetz-Boutaud, N, Kenealy, SJ, Jiang, L, Bartlett, J, Lynch, B, Gaskell, PC, Gwirtsman, H, McFarland, L, Bembe, ML, Bronson, P, Gilbert, J, Martin, ER, Pericak-Vance, MA & Haines, JL 2006, 'Covariate analysis of late-onset Alzheimer disease refines the chromosome 12 locus', Molecular Psychiatry, vol. 11, no. 3, pp. 280-285. https://doi.org/10.1038/sj.mp.4001766
Liang X, Schnetz-Boutaud N, Kenealy SJ, Jiang L, Bartlett J, Lynch B et al. Covariate analysis of late-onset Alzheimer disease refines the chromosome 12 locus. Molecular Psychiatry. 2006 Mar 1;11(3):280-285. https://doi.org/10.1038/sj.mp.4001766
Liang, X. ; Schnetz-Boutaud, N. ; Kenealy, S. J. ; Jiang, L. ; Bartlett, J. ; Lynch, B. ; Gaskell, P. C. ; Gwirtsman, H. ; McFarland, L. ; Bembe, M. L. ; Bronson, P. ; Gilbert, John ; Martin, Eden R ; Pericak-Vance, Margaret A ; Haines, J. L. / Covariate analysis of late-onset Alzheimer disease refines the chromosome 12 locus. In: Molecular Psychiatry. 2006 ; Vol. 11, No. 3. pp. 280-285.
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