Accounting for disease model uncertainty in mapping heterogeneous traits--a Bayesian model averaging approach.
Hum Hered
; 69(4): 242-53, 2010.
Article
em En
| MEDLINE
| ID: mdl-20339303
ABSTRACT
BACKGROUND:
Locus heterogeneity, wherein a disease can be caused in different individuals by different genes and/or environmental factors, is a ubiquitous feature of complex traits. A Bayesian approach has been proposed to account for variable rates of heterogeneity across families in a parametric linkage analysis setup [Biswas and Lin J Am Stat Assoc 2006;1011341-1351]. As with any parametric approach, its application requires specification of the disease model, which limits its practical utility.METHODS:
We address this limitation by proposing a Bayesian model averaging (BMA) approach. We consider a finite number of disease models and treat the model as an unknown parameter. In practice, we use simple single-locus disease models as various categories for model.RESULTS:
Our simulations as well as analysis of Genetic Analysis Workshop 13 simulated data show that BMA retains at least 80% of the power that is obtained by analyzing under the true disease model. The coverage probability of interval for disease gene is maintained around the nominal level. Finally, we apply BMA to a Late-Onset Alzheimer's Disease dataset and find evidence for linkage on chromosomes 19, 9, and 21.CONCLUSION:
We conclude that the BMA approach utilizing simple single-locus models for averaging is effective for mapping heterogeneous traits.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Teorema de Bayes
/
Incerteza
/
Doença de Alzheimer
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Hum Hered
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos