title: Role of genes and environments for explaining Alzheimer disease.
abstract: 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.
authors.affiliation: Department of Psychology, University of Southern California, Los Angeles 90089-1061, USA. gatz@usc.edu
authors.forename: Margaret
authors.initials: M
authors.lastname: Gatz
authors.forename: Chandra A
authors.initials: CA
authors.lastname: Reynolds
authors.forename: Laura
authors.initials: L
authors.lastname: Fratiglioni
authors.forename: Boo
authors.initials: B
authors.lastname: Johansson
authors.forename: James A
authors.initials: JA
authors.lastname: Mortimer
authors.forename: Stig
authors.initials: S
authors.lastname: Berg
authors.forename: Amy
authors.initials: A
authors.lastname: Fiske
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Pedersen
mesh_terms: 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