Impact of Sample Selection on APOE ∈4 Allele Frequency: A Comparison of Two Alzheimer's Disease Samples
This study is supported in part by National Institute of Aging Grants R01 AG07584, U01 AG06781, and P50 AG05136.
Previous versions of this manuscript were presented as a Young Investigator Oral Presentation at the American Psychiatric Association Annual Meeting, Philadelphia, Pennsylvania, in May 1994, and as a poster at the Fourth International Conference on Alzheimer's Disease and Related Disorders, Minneapolis, Minnesota, in August 1994.
Abstract
OBJECTIVE: In a highly selected sample of unrelated Alzheimer's disease (AD) patients, we found that the APOE ∈4 allele frequency was higher than previously reported. Differing selection and ascertainment criteria may lead to these differences. To address this possibility, we compared the ∈4 allele frequency in two samples of AD patients selected from the same geographical area.
SETTING AND PARTICIPANTS: Cases (n = 55) and controls (n = 99) from a research clinic-based sample were compared with subjects (n = 537) from a community-based AD patient sample. The samples consisted of unrelated cases who met NINCDS/ADRDA criteria for probable AD.
DESIGN AND MEASUREMENTS: Clinical characteristics and APOE genotype data were obtained from AD cases and controls from both samples.
RESULTS: Frequency of APOE ∈4 allele in the research cases compared with the community cases (0.45 vs 0.36) was nearly significant. We compared demographic and clinical characteristics that might account for this difference and found that the research cases were younger, had an earlier age of onset, and had more advanced disease than the community cases. After onset age was controlled, there was no overall difference between ∈4 allele frequency of the two samples.
CONCLUSIONS: We found that the ∈4 allele frequency tended to be higher in the research AD sample compared the community-based sample. The two samples differed in several demographic and clinical characteristics. We conclude that research-based samples may lead to enrollment of younger patients with more severe disease who have higher APOE ∈4 allele load. This potential selection bias must be considered in the interpretation of studies of APOE allele frequency.
