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Title: 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:
; ; ; ;  [1];  [2]
  1. Harvard Medical School, Boston, MA (United States)
  2. 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}
}