Further evidence of a maternal parent-of-origin effect on chromosome 10 in late-onset Alzheimer's disease

• Published in: American journal of medical genetics. Part B, Neuropsychiatric genetics Neuropsychiatric genetics, 2006-07, Vol.141B (5), p.537-540
• Main Authors: Bassett, Susan Spear, Avramopoulos, Dimitrios, Perry, Rodney T., Wiener, Howard, Watson Jr, Bracie, Go, Rodney C. P., Fallin, M. Daniele
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - genetics; Alzheimer's disease; Biological and medical sciences; Chromosomes, Human, Pair 10 - genetics; Classical genetics, quantitative genetics, hybrids; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Family Health; Female; Fundamental and applied biological sciences. Psychology; genetic imprinting; Genetic Linkage; Genetics of eukaryotes. Biological and molecular evolution; Genome, Human; Human; human chromosome 10; Humans; linkage; Lod Score; Male; Medical sciences; Microsatellite Repeats - genetics; Mothers; Neurology; Pedigree
• ISSN: 1552-4841; 1552-485X
• DOI: 10.1002/ajmg.b.30350

The chromosome 10q region has recently received a great deal of attention in late‐onset Alzheimer's disease (LOAD), given the growing evidence of linkage to LOAD, or to A‐beta levels, reported by several groups. In a recent paper we reported evidence of linkage in this region in our subset of the NIMH AD genetics initiative pedigrees, approaching genome‐wide significance (non‐parametric LOD score = 3.27), when only families with maternal disease origin were analyzed [Bassett et al. (2002); Am J Med Genet 114:679–686]. We have now extended this work, using an independent subset of NIMH AD pedigrees from the University of Alabama at Birmingham (UAB), and show further evidence of linkage using parent‐of‐origin information. As in our Hopkins sample, maternal but not paternal pedigrees show significantly increased linkage in the chromosome 10q region compared to the unstratified sample. Combining data from our previous fine‐mapping work on this region and five new markers genotyped in all pedigrees results in a non‐parametric LOD score of 3.73 in the same region, a value that reaches genome wide significance for linkage, with an empirical P value = 0.003. These results support our earlier findings and narrow the region of interest. In combination with findings from other groups, these results provide further evidence that this chromosome 10 region harbors a gene implicated in LOAD, and our use of parent‐of‐origin information has been useful in further narrowing the region of interest. © 2006 Wiley‐Liss, Inc.