We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Genetic studies on chromosome 12 in late-onset Alzheimer disease.
- Authors
Wu, William S.; Holmans, Peter; Wavrant-DeVrieze, Fabienne; Shears, Shantia; Kehoe, Patrick; Crook, Richard; Booth, Jeremy; Williams, Nigel; Perez-Tur, Jordi; Roehl, Kimberely; Fenton, Iain; Chartier-Harlin, Marie-Christine; Lovestone, Simon; Williams, Julie; Hutton, Mike; Hardy, John; Owen, Michael J.; Goate, Alison; Wu, W S; Holmans, P
- Abstract
<bold>Context: </bold>The only genetic locus universally accepted to be important as a risk factor for late-onset Alzheimer disease (AD) is the apolipoprotein E (APOE) locus on chromosome 19. However, this locus does not account for all the risk in late-onset disease, and a recent report has suggested a second locus on chromosome 12p11-12.<bold>Objective: </bold>To look for evidence of linkage on chromosome 12 and to test for the presence of the new locus in an independent sample of familial late-onset AD cases.<bold>Design: </bold>Retrospective cohort study. As part of a 20-centimorgan genome screen (approximately equal to 200 markers), we tested a series of 18 genetic markers on chromosome 12 and carried out multipoint, nonparametric lod score and exclusion analyses.<bold>Setting: </bold>Clinic populations in the continental United States selected from the National Institute of Mental Health AD Genetics Consortium.<bold>Patients: </bold>We selected samples for DNA analysis from affected sibling pairs, 497 subjects from 230 families with 2 or more affected individuals with probable or definite AD with onset ages older than 60 years (mean+/-SD, 75+/-6 years). Within the families, we used the 2 probable or definitely affected individuals. In families with more than 2 such cases available, we used all of them; in families with only 2 such cases in which unaffected individuals were available, we also sampled the oldest unaffected individual and used genotype data from this unaffected individual to check for nonpaternity and genotyping errors.<bold>Main Outcome Measure: </bold>Presence of linkage or locus on chromosome 12.<bold>Results: </bold>Although linkage analyses confirmed the presence of a genetic susceptibility factor at the APOE locus in these families with late-onset AD, we were unable to confirm the presence of a locus close to the marker D12S1042. A moderate lod score (1.91) was found near D12S98 close to the alpha2-macroglobulin locus in the affected pairs in which both members did not possess an APOE epsilon4 allele.<bold>Conclusions: </bold>APOE remains the only locus established to be a risk factor for late-onset AD. We were unable to confirm that a locus on chromosome 12p11-12 has a major effect on risk for late-onset AD, although an effect smaller than that for APOE cannot be excluded.
- Subjects
GENETICS of Alzheimer's disease; FAMILIAL diseases; CHROMOSOMES; MEMORY disorders in old age
- Publication
JAMA: Journal of the American Medical Association, 1998, Vol 280, Issue 7, p619
- ISSN
0098-7484
- Publication type
journal article
- DOI
10.1001/jama.280.7.619