Detecting rare and common haplotype-environment interaction under uncertainty of gene-environment independence assumption.
Biometrics
; 73(1): 344-355, 2017 03.
Article
en En
| MEDLINE
| ID: mdl-27478935
ABSTRACT
Finding rare variants and gene-environment interactions (GXE) is critical in dissecting complex diseases. We consider the problem of detecting GXE where G is a rare haplotype and E is a nongenetic factor. Such methods typically assume G-E independence, which may not hold in many applications. A pertinent example is lung cancer-there is evidence that variants on Chromosome 15q25.1 interact with smoking to affect the risk. However, these variants are associated with smoking behavior rendering the assumption of G-E independence inappropriate. With the motivation of detecting GXE under G-E dependence, we extend an existing approach, logistic Bayesian LASSO, which assumes G-E independence (LBL-GXE-I) by modeling G-E dependence through a multinomial logistic regression (referred to as LBL-GXE-D). Unlike LBL-GXE-I, LBL-GXE-D controls type I error rates in all situations; however, it has reduced power when G-E independence holds. To control type I error without sacrificing power, we further propose a unified approach, LBL-GXE, to incorporate uncertainty in the G-E independence assumption by employing a reversible jump Markov chain Monte Carlo method. Our simulations show that LBL-GXE has power similar to that of LBL-GXE-I when G-E independence holds, yet has well-controlled type I errors in all situations. To illustrate the utility of LBL-GXE, we analyzed a lung cancer dataset and found several significant interactions in the 15q25.1 region, including one between a specific rare haplotype and smoking.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fumar
/
Biometría
/
Interacción Gen-Ambiente
/
Neoplasias Pulmonares
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Biometrics
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos