Role of genes and environments for explaining Alzheimer disease.
BACKGROUND
Twin studies using selected samples have shown high heritability for Alzheimer disease (AD).


OBJECTIVE
To evaluate genetic and environmental influences on AD in a fully ascertained population of older twins, including like- and unlike-sex pairs.


METHODS
Five-group quantitative genetic model: male monozygotic twins, female monozygotic twins, male dizygotic twins, female dizygotic twins, and unlike-sex twins.


METHODS
All twins in the Swedish Twin Registry aged 65 years and older. The study included 11,884 twin pairs, among whom were 392 pairs in which 1 or both members had AD.


METHODS
All individuals were screened for cognitive dysfunction. Suspected cases of dementia and their co-twins received complete clinical diagnostic evaluations for AD. Estimates of heritability, shared environmental influences, and nonshared environmental influences, adjusting for age, were derived from the twin data.


RESULTS
Heritability for AD was estimated to be 58% in the full model and 79% in the best-fitting model, with the balance of variation explained by nonshared environmental influences. There were no significant differences between men and women in prevalence or heritability after controlling for age. Within pairs concordant for AD, intrapair difference in age at onset was significantly greater in dizygotic than in monozygotic pairs, suggesting genetic influences on timing of the disease.


CONCLUSIONS
In the largest twin study to date, we confirmed that heritability for AD is high and that the same genetic factors are influential for both men and women. However, nongenetic risk factors also play an important role and might be the focus for interventions to reduce disease risk or delay disease onset.
Gatz
Margaret
M
Department of Psychology, University of Southern California, Los Angeles 90089-1061, USA. gatz@usc.edu
Reynolds
Chandra A
CA
Fratiglioni
Laura
L
Johansson
Boo
B
Mortimer
James A
JA
Berg
Stig
S
Fiske
Amy
A
Pedersen
Nancy L
NL
D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics*; D015331:Cohort Studies; D004200:Diseases in Twins / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000209:etiology / Q000235:genetics; D006801:Humans; D008297:Male; D008957:Models, Genetic; D010641:Phenotype; D015995:Prevalence; D012042:Registries / Q000706:statistics & numerical data; D012307:Risk Factors; D012737:Sex Factors; D012931:Social Environment; D013548:Sweden / Q000453:epidemiology; D014429:Twins, Dizygotic / Q000235:genetics; D014430:Twins, Monozygotic / Q000235:genetics