Generalized genetic association study with samples of related individuals

DOI10.1214/11-AOAS465zbMATH Open1228.62140arXiv1111.5487MaRDI QIDQ652373FDOQ652373

Authors: William W. L. Wong, Xin Gao, Flavio Schenkel, Zeny Z. Feng 

Publication date: 14 December 2011

Published in: The Annals of Applied Statistics (Search for Journal in Brave)

Abstract: Genetic association study is an essential step to discover genetic factors that are associated with a complex trait of interest. In this paper we present a novel generalized quasi-likelihood score (GQLS) test that is suitable for a study with either a quantitative trait or a binary trait. We use a logistic regression model to link the phenotypic value of the trait to the distribution of allelic frequencies. In our model, the allele frequencies are treated as a response and the trait is treated as a covariate that allows us to leave the distribution of the trait values unspecified. Simulation studies indicate that our method is generally more powerful in comparison with the family-based association test (FBAT) and controls the type I error at the desired levels. We apply our method to analyze data on Holstein cattle for an estimated breeding value phenotype, and to analyze data from the Collaborative Study of the Genetics of Alcoholism for alcohol dependence. The results show a good portion of significant SNPs and regions consistent with previous reports in the literature, and also reveal new significant SNPs and regions that are associated with the complex trait of interest.

Full work available at URL: https://arxiv.org/abs/1111.5487

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zbMATH Keywords

logistic regressionquasi-likelihoodgenetic association testkinship-inbreeding coefficient

Mathematics Subject Classification ID

Nonparametric hypothesis testing (62G10) Applications of statistics to biology and medical sciences; meta analysis (62P10) Hypothesis testing in multivariate analysis (62H15) Generalized linear models (logistic models) (62J12) Genetics and epigenetics (92D10) Testing in survival analysis and censored data (62N03)

Cites Work

• Title not available (Why is that?)
• Quasi-likelihood and its application. A general approach to optimal parameter estimation
• Multiple outputation: inference for complex clustered data by averaging analyses from independent data
• Generalized genetic association study with samples of related individuals

Cited In (8)

• Unifying genetic association tests via regression: Prospective and retrospective, parametric and nonparametric, and genotype‐ and allele‐based tests
• A generalized robust allele‐based genetic association test
• SNP selection for predicting a quantitative trait
• The generalized odds ratio as a measure of genetic risk effect in the analysis and meta-analysis of association studies
• Association study for the relationship between a haplotype or haplotype set and multiple quantitative responses
• Generalized genetic association study with samples of related individuals
• A genome-wide association study of multiple longitudinal traits with related subjects
• The power of generalized odds ratio in assessing association in genetic studies with known mode of inheritance

Uses Software

• R
• KinInbcoef
• CFC

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