Influence of apolipoprotein E genotype on the transmission of Alzheimer disease in a community-based sample

Journal Article · Mon Jan 01 00:00:00 EST 1996 · American Journal of Human Genetics

OSTI ID:232387

Jarvik, G P; Larson, E B; Goddard, K ^[1]

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1. Univ. of Washington Medical Center, Seattle, WA (United States); and others

The {epsilon}4 allele of the apolipoprotein E locus (APOE) has been found to be an important predictor of Alzheimer disease (AD). However, linkage analysis has not clarified the role of APOE in the transmission of AD. The results of the current study provide evidence that the pattern of transmission of memory disorders differs in nuclear families in which the AD-affected proband did carry an {epsilon}4 allele versus those families in which the AD-affected proband did not carry an {epsilon}4 allele. Further, risk of AD due to APOE genotype in the probands is modified by family history of memory disorders, suggesting gene-by-gene interactions. Family history remained a significant predictor of AD for affected probands with some, but not all, APOE genotypes in a logistic regression analysis. Though nonadditive in the prediction of AD, APOE genotype and family history acted additively in the prediction of age at AD onset. The results of complex segregation analysis were inconsistent with Mendelian segregation of memory disorders both in families of affected probands who did or did not carry an {epsilon}4 allele, yet these two groups had significantly different parameter estimates for their transmission models. These results are consistent with gene-by-gene interactions, but also could result from common elements in the familial environment. 41 refs., 1 fig., 7 tabs.

• OSTI ID: 232387
• Journal Information: American Journal of Human Genetics, Vol. 58, Issue 1; Other Information: PBD: Jan 1996
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
99 MATHEMATICS
COMPUTERS
INFORMATION SCIENCE
MANAGEMENT
LAW
MISCELLANEOUS
APOLIPOPROTEINS
GENES
PATIENTS
GENOTYPE
HEREDITARY DISEASES
MENTAL DISORDERS
NERVOUS SYSTEM DISEASES
GENETICS
AGE DEPENDENCE
PARAMETRIC ANALYSIS
MATHEMATICAL MODELS
GENETIC MAPPING
GENE MUTATIONS
HUMAN CHROMOSOMES
STATISTICS