Dataset Information

A two-stage testing strategy for detecting genes×environment interactions in association studies.

ABSTRACT: Identifying gene×environment (G×E) interactions, especially when rare variants are included in genome-wide association studies, is a major challenge in statistical genetics. However, the detection of G×E interactions is very important for understanding the etiology of complex diseases. Although currently some statistical methods have been developed to detect the interactions between genes and environment, the detection of the interactions for the case of rare variants is still limited. Therefore, it is particularly important to develop a new method to detect the interactions between genes and environment for rare variants. In this study, we extend an existing method of adaptive combination of P-values (ADA) and design a novel strategy (called iSADA) for testing the effects of G×E interactions for rare variants. We propose a new two-stage test to detect the interactions between genes and environment in a certain region of a chromosome or even for the whole genome. First, the score statistic is used to test the associations between trait value and the interaction terms of genes and environment and obtain the original P-values. Then, based on the idea of the ADA method, we further construct a full test statistic via the P-values of the preliminary tests in the first stage, so that we can comprehensively test the interactions between genes and environment in the considered genome region. Simulation studies are conducted to compare our proposed method with other existing methods. The results show that the iSADA has higher power than other methods in each case. A GAW17 data set is also applied to illustrate the applicability of the new method.

SUBMITTER: Zhou J

PROVIDER: S-EPMC8496220 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BACKGROUND: Association mapping studies offer great promise to identify polymorphisms associated with phenotypes and for understanding the genetic basis of quantitative trait variation. To date, almost all association mapping studies based on structured plant populations examined the main effects of genetic factors on the trait but did not deal with interactions between genetic factors and environment. In this paper, we propose a methodological prospect of mixed linear models to analyze genotype by environment interaction effects using association mapping designs. First, we simulated datasets to assess the power of linear mixed models to detect interaction effects. This simulation was based on two association panels composed of 90 inbreds (pearl millet) and 277 inbreds (maize). RESULTS: Based on the simulation approach, we reported the impact of effect size, environmental variation, allele frequency, trait heritability, and sample size on the power to detect the main effects of genetic loci and diverse effect of interactions implying these loci. Interaction effects specified in the model included SNP by environment interaction, ancestry by environment interaction, SNP by ancestry interaction and three way interactions. The method was finally used on real datasets from field experiments conducted on the two considered panels. We showed two types of interactions effects contributing to genotype by environment interactions in maize: SNP by environment interaction and ancestry by environment interaction. This last interaction suggests differential response at the population level in function of the environment. CONCLUSIONS: Our results suggested the suitability of mixed models for the detection of diverse interaction effects. The need of samples larger than that commonly used in current plant association studies is strongly emphasized to ensure rigorous model selection and powerful interaction assessment. The use of ancestry interaction component brought valuable information complementary to other available approaches.

Dataset Information

A two-stage testing strategy for detecting genes×environment interactions in association studies.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets