Composite kernel machine regression based on likelihood ratio test for joint testing of genetic and gene–environment interaction effect

Biometrics ◽  
2019 ◽  
Vol 75 (2) ◽  
pp. 625-637 ◽  
Author(s):  
Ni Zhao ◽  
Haoyu Zhang ◽  
Jennifer J. Clark ◽  
Arnab Maity ◽  
Michael C. Wu
Author(s):  
Shuo Jiao

This chapter presents set-based approaches that focus on identifying G X E interactions rather than set-based approaches that are based primarily on detecting G main effects (e.g., via marginal effects). The author reviews both his own research and the development of his Set Based Gene EnviRonment InterAction test (SBERIA), as well as another set-based G X E approach referred to as GESAT. GESAT extends the variance component test of the SNP-set Kernel Association Test (SKAT) to evaluate G x E effects while incorporating the main SNP effects as covariates. While both of these approaches (SBERIA and GESAT) have outperformed other benchmark methods (e.g., likelihood ratio test) and have been demonstrated to retain the appropriate Type 1 error rate, in this chapter the author conducts simulation studies to compare findings for SBERIA and GESAT approaches, and identifies associated strengths and limitations of the respective methods.


1997 ◽  
Vol 78 (01) ◽  
pp. 457-461 ◽  
Author(s):  
S E Humphries ◽  
A Panahloo ◽  
H E Montgomery ◽  
F Green ◽  
J Yudkin

2020 ◽  
Vol 16 (5) ◽  
pp. 457-470 ◽  
Author(s):  
Mohammad H. Zafarmand ◽  
Parvin Tajik ◽  
René Spijker ◽  
Charles Agyemang

Background: The body of evidence on gene-environment interaction (GEI) related to type 2 diabetes (T2D) has grown in the recent years. However, most studies on GEI have sought to explain variation within individuals of European ancestry and results among ethnic minority groups are inconclusive. Objective: To investigate any interaction between a gene and an environmental factor in relation to T2D among ethnic minority groups living in Europe and North America. Methods: We systematically searched Medline and EMBASE databases for the published literature in English up to 25th March 2019. The screening, data extraction and quality assessment were performed by reviewers independently. Results: 1068 studies identified through our search, of which nine cohorts of six studies evaluating several different GEIs were included. The mean follow-up time in the included studies ranged from 5 to 25.7 years. Most studies were relatively small scale and few provided replication data. All studies included in the review included ethnic minorities from North America (Native-Americans, African- Americans, and Aboriginal Canadian), none of the studies in Europe assessed GEI in relation to T2D incident in ethnic minorities. The only significant GEI among ethnic minorities was HNF1A rs137853240 and smoking on T2D incident among Native-Canadians (Pinteraction = 0.006). Conclusion: There is a need for more studies on GEI among ethnicities, broadening the spectrum of ethnic minority groups being investigated, performing more discovery using genome-wide approaches, larger sample sizes for these studies by collaborating efforts such as the InterConnect approach, and developing a more standardized method of reporting GEI studies are discussed.


Author(s):  
Andrey Ziyatdinov ◽  
Jihye Kim ◽  
Dmitry Prokopenko ◽  
Florian Privé ◽  
Fabien Laporte ◽  
...  

Abstract The effective sample size (ESS) is a metric used to summarize in a single term the amount of correlation in a sample. It is of particular interest when predicting the statistical power of genome-wide association studies (GWAS) based on linear mixed models. Here, we introduce an analytical form of the ESS for mixed-model GWAS of quantitative traits and relate it to empirical estimators recently proposed. Using our framework, we derived approximations of the ESS for analyses of related and unrelated samples and for both marginal genetic and gene-environment interaction tests. We conducted simulations to validate our approximations and to provide a quantitative perspective on the statistical power of various scenarios, including power loss due to family relatedness and power gains due to conditioning on the polygenic signal. Our analyses also demonstrate that the power of gene-environment interaction GWAS in related individuals strongly depends on the family structure and exposure distribution. Finally, we performed a series of mixed-model GWAS on data from the UK Biobank and confirmed the simulation results. We notably found that the expected power drop due to family relatedness in the UK Biobank is negligible.


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