 |
|
Role of Genes and Environments for Explaining Alzheimer Disease
Margaret Gatz, PhD;
Chandra A. Reynolds, PhD;
Laura Fratiglioni, MD, PhD;
Boo Johansson, PhD;
James A. Mortimer, PhD;
Stig Berg, PhD;
Amy Fiske, PhD;
Nancy L. Pedersen, PhD
Arch Gen Psychiatry. 2006;63:168-174.
Context 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.
Design Five-group quantitative genetic model: male monozygotic twins, female monozygotic twins, male dizygotic twins, female dizygotic twins, and unlike-sex twins.
Setting and Participants 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.
Main Outcome Measures 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.
Author Affiliations: Department of Psychology, University of Southern California, Los Angeles (Drs Gatz, Fiske, and Pedersen); Department of Medical Epidemiology and Biostatistics (Drs Gatz and Pedersen) and Aging Research Center (Dr Fratiglioni), Karolinska Institutet, Stockholm, Sweden; Department of Psychology, University of California at Riverside (Dr Reynolds); Department of Psychology, Göteborg University, Göteborg, Sweden (Dr Johansson); Department of Epidemiology and Biostatistics, University of South Florida, Tampa (Dr Mortimer); Institute of Gerontology, School of Health Sciences, Jönköping University, Jönköping, Sweden (Dr Berg); and Department of Psychology, West Virginia University, Morgantown (Dr Fiske).
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter
What's this?
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Vascular Factors and Markers of Inflammation in Offspring With a Parental History of Late-Onset Alzheimer Disease
van Exel et al.
Arch Gen Psychiatry 2009;66:1263-1270.
ABSTRACT
| FULL TEXT
Parental history of Alzheimer disease associated with lower plasma apolipoprotein E levels
van Vliet et al.
Neurology 2009;73:681-687.
ABSTRACT
| FULL TEXT
Voxel-based analysis of cerebral glucose metabolism in mono- and dizygotic twins discordant for Alzheimer disease
Virta et al.
J. Neurol. Neurosurg. Psychiatry 2009;80:259-266.
ABSTRACT
| FULL TEXT
GAB2 as an Alzheimer Disease Susceptibility Gene: Follow-up of Genomewide Association Results
Schjeide et al.
Arch Neurol 2009;66:250-254.
ABSTRACT
| FULL TEXT
Genetic Epidemiology in Aging Research
Fallin and Matteini
J Gerontol A Biol Sci Med Sci 2009;0:gln021v1-gln021.
ABSTRACT
| FULL TEXT
Bibliography: Geriatric Psychiatry
Focus 2009;7:46-48.
FULL TEXT
Mid- and Late-Life Diabetes in Relation to the Risk of Dementia: A Population-Based Twin Study
Xu et al.
Diabetes 2009;58:71-77.
ABSTRACT
| FULL TEXT
Geographical Differences in the Occurrence of Alzheimer's Disease Mortality: United States Versus Puerto Rico
Figueroa et al.
AM J ALZHEIMERS DIS OTHER DEMEN 2008;23:462-469.
ABSTRACT
Association study of the NEDD9 gene with the risk of developing Alzheimer's and Parkinson's disease
Chapuis et al.
Hum Mol Genet 2008;17:2863-2867.
ABSTRACT
| FULL TEXT
Doctors' health and fitness to practise: performance problems in doctors and cognitive impairments
Pitkanen et al.
Occup Med (Lond) 2008;58:328-333.
ABSTRACT
| FULL TEXT
Evidence that common variation in NEDD9 is associated with susceptibility to late-onset Alzheimer's and Parkinson's disease
Li et al.
Hum Mol Genet 2008;17:759-767.
ABSTRACT
| FULL TEXT
n-3 Fatty acid erythrocyte membrane content, APOE {varepsilon}4, and cognitive variation: an observational follow-up study in late adulthood
Whalley et al.
Am. J. Clin. Nutr. 2008;87:449-454.
ABSTRACT
| FULL TEXT
Physical Exercise at Midlife and Risk of Dementia Three Decades Later: A Population-Based Study of Swedish Twins
Andel et al.
Journals of Gerontology Series A: Biological Sciences and Medical Sciences 2008;63:62-66.
ABSTRACT
| FULL TEXT
Genome-wide linkage analysis of 723 affected relative pairs with late-onset Alzheimer's disease
Hamshere et al.
Hum Mol Genet 2007;16:2703-2712.
ABSTRACT
| FULL TEXT
Clinicopathological concordance and discordance in three monozygotic twin pairs with familial Alzheimer's disease
Brickell et al.
J. Neurol. Neurosurg. Psychiatry 2007;78:1050-1055.
ABSTRACT
| FULL TEXT
Decreased Catalytic Activity of the Insulin-degrading Enzyme in Chromosome 10-Linked Alzheimer Disease Families
Kim et al.
J. Biol. Chem. 2007;282:7825-7832.
ABSTRACT
| FULL TEXT
New Alzheimer's disease locus on chromosome 8
Giedraitis et al.
J. Med. Genet. 2006;43:931-935.
ABSTRACT
| FULL TEXT
Genetic Susceptibility to Retinopathy of Prematurity
Bizzarro et al.
Pediatrics 2006;118:1858-1863.
ABSTRACT
| FULL TEXT
Dementia--Epidemiological Considerations, Nomenclature, and a Tacit Consensus Definition
Breitner
J Geriatr Psychiatry Neurol 2006;19:129-136.
ABSTRACT
The Genetic Contribution to Alzheimer Disease
JWatch Neurology 2006;2006:6-6.
FULL TEXT
The Genetic Contribution to Alzheimer Disease
JWatch Psychiatry 2006;2006:6-6.
FULL TEXT
|
