Role of genes and environments for explaining Alzheimer disease.
Level 3 - non-randomized controlled study
Large population-based twin cohort study using quantitative genetic modeling
PubMed 16461860 · doi:10.1001/archpsyc.63.2.168
What was done
All twin pairs aged 65 years and older from the Swedish Twin Registry (11,884 pairs) were screened for cognitive dysfunction. Suspected dementia cases and their co-twins received complete clinical diagnostic evaluations for Alzheimer disease (AD), yielding 392 pairs where one or both members were affected. A five-group quantitative genetic model (male monozygotic, female monozygotic, male dizygotic, female dizygotic, and unlike-sex pairs) was used to estimate age-adjusted heritability and shared versus nonshared environmental influences.
What was found
Heritability of AD was estimated to be 58% in the full model and 79% in the best-fitting model, with nonshared environmental influences explaining the balance of variation. There were no significant differences in prevalence or heritability between men and women after controlling for age. Among concordant pairs, intrapair difference in age at onset was significantly larger in dizygotic pairs than in monozygotic pairs.
Why it matters
This study provides large population-based confirmation that genetic variation strongly influences Alzheimer disease risk and onset age across sexes, while establishing that nonshared environmental factors account for a substantial remaining fraction of risk.
Limits
The study is restricted to the Swedish population, potentially limiting generalizability to other demographic or ancestral groups. The abstract does not identify specific environmental exposures, specific genetic variants, or biomarker profiles.
Cited by
- contradicts Only about 10% to 15% of the risk for chronic disease is genetic, while 85% to 90% is determined by environmental and lifestyle factors.