Bertram et al. (301.7), evaluated Alzheimer’s disease (AD) candidate genes and AD chromosomal regions of interest (`30 cM) from the whole genome scans available from the National Institutes of Mental Health-Alzheimer Disease ((NIMH-AD) Genetics Initiative Program. These NIMH population samples, consisting of about 500 sibling pairs, is one of the largest AD study populations collected to date. This rather large and well characterized sample has, therefore, sufficient statistical power to score genes potentially involved in the etiopathogenesis of aging, AD and other neurodegenerative disorders.
The authors performed this genome scan analysis at three potential sites on 1000 subjects [obtained from 300 NMIH-AD participating families. In summary, these analyses revealed 16 novel, putative AD chromosomal regions of interest involving unlinked genetic loci on human chromosomes 1, 3, 4, 5, 6, 8, 9, 10, 11, 12, 13, 16, 21 and X.
FASTLINK and the Sibship Disequilibrium Test (SDT; a family-based association test that can be used in the absence of parental data ) was also used to score for potential AD genetic loci in these analyses. To confirm that this approach was valid, results of LOD scoring, affected pedigree member analysis, and sib-pair analysis supported ApoE-4 as a strong risk factor for AD (previously known). A ~30 cM region on chromosome 10 showed linkage to AD with a log of the odds (LOD) score of 2-3. Interestingly, the newly discovered nicastrin gene and the gene for presenilin-2 (PS2) both lie in rather close proximity on the long arm of human chromosome 1, another potential AD locus. (See also Tanzi et al., Blacker et al).—Walter Lukiw
References: Session 301.7. Bertram DL, Blacker J, Jones D, Keeney K, Mullin S, Basu S, Yhu R, Go M, McInnis RE, Tanzi. Testing for genetic association and linkage in Alzheimer disease: Results of the NIMH study.
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