Dataset Information

A new efficient method to detect genetic interactions for lung cancer GWAS.

ABSTRACT:

Background

Genome-wide association studies (GWAS) have proven successful in predicting genetic risk of disease using single-locus models; however, identifying single nucleotide polymorphism (SNP) interactions at the genome-wide scale is limited due to computational and statistical challenges. We addressed the computational burden encountered when detecting SNP interactions for survival analysis, such as age of disease-onset. To confront this problem, we developed a novel algorithm, called the Efficient Survival Multifactor Dimensionality Reduction (ES-MDR) method, which used Martingale Residuals as the outcome parameter to estimate survival outcomes, and implemented the Quantitative Multifactor Dimensionality Reduction method to identify significant interactions associated with age of disease-onset.

Methods

To demonstrate efficacy, we evaluated this method on two simulation data sets to estimate the type I error rate and power. Simulations showed that ES-MDR identified interactions using less computational workload and allowed for adjustment of covariates. We applied ES-MDR on the OncoArray-TRICL Consortium data with 14,935 cases and 12,787 controls for lung cancer (SNPs?=?108,254) to search over all two-way interactions to identify genetic interactions associated with lung cancer age-of-onset. We tested the best model in an independent data set from the OncoArray-TRICL data.

Results

Our experiment on the OncoArray-TRICL data identified many one-way and two-way models with a single-base deletion in the noncoding region of BRCA1 (HR 1.24, P?=?3.15?×?10^-15), as the top marker to predict age of lung cancer onset.

Conclusions

From the results of our extensive simulations and analysis of a large GWAS study, we demonstrated that our method is an efficient algorithm that identified genetic interactions to include in our models to predict survival outcomes.

SUBMITTER: Luyapan J

PROVIDER: S-EPMC7596958 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Publications

A new efficient method to detect genetic interactions for lung cancer GWAS.

Luyapan Jennifer J Ji Xuemei X Li Siting S Xiao Xiangjun X Zhu Dakai D Duell Eric J EJ Christiani David C DC Schabath Matthew B MB Arnold Susanne M SM Zienolddiny Shanbeh S Brunnström Hans H Melander Olle O Thornquist Mark D MD MacKenzie Todd A TA Amos Christopher I CI Gui Jiang J

BMC medical genomics 20201030 1

<h4>Background</h4>Genome-wide association studies (GWAS) have proven successful in predicting genetic risk of disease using single-locus models; however, identifying single nucleotide polymorphism (SNP) interactions at the genome-wide scale is limited due to computational and statistical challenges. We addressed the computational burden encountered when detecting SNP interactions for survival analysis, such as age of disease-onset. To confront this problem, we developed a novel algorithm, calle ...[more]

PMID: 33126877

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Dataset Information

A new efficient method to detect genetic interactions for lung cancer GWAS.

Background

Methods

Results

Conclusions

Publications

A new efficient method to detect genetic interactions for lung cancer GWAS.

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