Multiple etiologies for Alzheimer disease are revealed by segregation analysis
Abstract
We have evaluated several transmission models for Alzheimer disease (AD), using the logistic regressive approach in 401 nuclear families of consecutively ascertained and rigorously diagnosed probands. Models postulating no major gene effect, random environmental transmission, recessive inheritance, and sporadic occurrence were rejected under varied assumptions regarding the associations among sex, age, and major gene susceptibility. Transmission of the disorder was not fully explained by a single Mendelian model for all families. Stratification of families as early- and late-onset by using the median of family mean onset ages showed that, regardless of the model studied, two groups of families fit better than a single group. AD in early-onset families is transmitted as an autosomal dominant trait with full penetrance in both sexes and has a gene frequency of 1.5%. Dominant inheritance also gave the best fit of the data in late-onset families, but this hypothesis was rejected, suggesting the presence of heterogeneity within this subset. Our study also revealed that genetically nonsusceptible males and females develop AD, indicating the presence of phenocopies within early-onset and late-onset groups. Moreover, our results suggest that the higher risk to females is not solely due to their increased longevity. 50 refs., 5 tabs.
- Authors:
-
- Harvard Medical School, Boston, MA (United States)
- Erasmus Univ., Rotterdam (Netherlands)
- Publication Date:
- OSTI Identifier:
- 56846
- Resource Type:
- Journal Article
- Journal Name:
- American Journal of Human Genetics
- Additional Journal Information:
- Journal Volume: 55; Journal Issue: 5; Other Information: PBD: Nov 1994
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 55 BIOLOGY AND MEDICINE, BASIC STUDIES; HEREDITARY DISEASES; ETIOLOGY; HUMAN POPULATIONS; GENETIC EFFECTS; SEX DEPENDENCE; AGE DEPENDENCE; GENETICS; STATISTICAL MODELS; HUMAN CHROMOSOME 14; HUMAN CHROMOSOME 19; HUMAN CHROMOSOME 21
Citation Formats
Rao, V S, Connor-Lacke, L, Cupplies, L A, Growdon, J H, Farrer, L A, and Duijn, C.M. van. Multiple etiologies for Alzheimer disease are revealed by segregation analysis. United States: N. p., 1994.
Web.
Rao, V S, Connor-Lacke, L, Cupplies, L A, Growdon, J H, Farrer, L A, & Duijn, C.M. van. Multiple etiologies for Alzheimer disease are revealed by segregation analysis. United States.
Rao, V S, Connor-Lacke, L, Cupplies, L A, Growdon, J H, Farrer, L A, and Duijn, C.M. van. 1994.
"Multiple etiologies for Alzheimer disease are revealed by segregation analysis". United States.
@article{osti_56846,
title = {Multiple etiologies for Alzheimer disease are revealed by segregation analysis},
author = {Rao, V S and Connor-Lacke, L and Cupplies, L A and Growdon, J H and Farrer, L A and Duijn, C.M. van},
abstractNote = {We have evaluated several transmission models for Alzheimer disease (AD), using the logistic regressive approach in 401 nuclear families of consecutively ascertained and rigorously diagnosed probands. Models postulating no major gene effect, random environmental transmission, recessive inheritance, and sporadic occurrence were rejected under varied assumptions regarding the associations among sex, age, and major gene susceptibility. Transmission of the disorder was not fully explained by a single Mendelian model for all families. Stratification of families as early- and late-onset by using the median of family mean onset ages showed that, regardless of the model studied, two groups of families fit better than a single group. AD in early-onset families is transmitted as an autosomal dominant trait with full penetrance in both sexes and has a gene frequency of 1.5%. Dominant inheritance also gave the best fit of the data in late-onset families, but this hypothesis was rejected, suggesting the presence of heterogeneity within this subset. Our study also revealed that genetically nonsusceptible males and females develop AD, indicating the presence of phenocopies within early-onset and late-onset groups. Moreover, our results suggest that the higher risk to females is not solely due to their increased longevity. 50 refs., 5 tabs.},
doi = {},
url = {https://www.osti.gov/biblio/56846},
journal = {American Journal of Human Genetics},
number = 5,
volume = 55,
place = {United States},
year = {Tue Nov 01 00:00:00 EST 1994},
month = {Tue Nov 01 00:00:00 EST 1994}
}