Dataset Information

Fitting Proportional Odds Model to Case-Control data with Incorporating Hardy-Weinberg Equilibrium.

ABSTRACT: Genetic association studies have been proved to be an efficient tool to reveal the aetiology of many human complex diseases and traits. When the phenotype is binary, the logistic regression model is commonly employed to evaluate the association strength of the genetic variants predispose to human diseases because the maximum likelihood estimator of the odds ratio based on case-control data is equivalent to that from the same model by taking the data as being arisen prospectively. This equivalence does not hold for the proportional odds model and using it to analyze the case-control data directly often results in a substantial bias. Through putting a parameter of the minor allele frequency in the modified likelihood function under the condition that the Hardy-Weinberg equilibrium law holds within controls, a consistent estimator is obtained. On the basis of it, we construct a score test statistic to test whether the genetic variant is associated with the diseases. Simulation studies show that the proposed estimator has smaller mean squared error than the existing methods when the genetic effect size is away from zero and the proposed test statistic has a good control of type I error rate and is more powerful than the existing procedures. Application to 45 single nucleotide polymorphisms located in the region of TRAF1-C5 genes for the association with four-level anticyclic citrullinated protein antibody from Genetic Analysis Workshop 16 further demonstrates its performance.

SUBMITTER: Zhang W

PROVIDER: S-EPMC4660314 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Fitting Proportional Odds Model to Case-Control data with Incorporating Hardy-Weinberg Equilibrium.

Zhang Wei W Zhang Zehui Z Li Xinmin X Li Qizhai Q

Scientific reports 20151126

Genetic association studies have been proved to be an efficient tool to reveal the aetiology of many human complex diseases and traits. When the phenotype is binary, the logistic regression model is commonly employed to evaluate the association strength of the genetic variants predispose to human diseases because the maximum likelihood estimator of the odds ratio based on case-control data is equivalent to that from the same model by taking the data as being arisen prospectively. This equivalenc ...[more]

PMID: 26607176

Similar Datasets

Project description:Objective: Departure from Hardy Weinberg Equilibrium (HWE) may occur due to a variety of causes, including purifying selection, inbreeding, population substructure, copy number variation or genotyping error. We searched for specific characteristics of HWE-departure due to genotyping error. Methods: Genotypes of a random set of genetic variants were obtained from the Exome Aggregation Consortium (ExAC) database. Variants with <80% successful genotypes or with minor allele frequency (MAF) <1% were excluded. HWE-departure (d-HWE) was considered significant at p < 10E-05 and classified as d-HWE with loss of heterozygosity (LoH d-HWE) or d-HWE with excess heterozygosity (gain of heterozygosity: GoH d-HWE). Missing genotypes, variant type (single nucleotide polymorphism (SNP) vs. insertion/deletion); MAF, standard deviation (SD) of MAF across populations (MAF-SD) and copy number variation were evaluated for association with HWE-departure. Results: The study sample comprised 3,204 genotype distributions. HWE-departure was observed in 134 variants: LoH d-HWE in 41 (1.3%), GoH d-HWE in 93 (2.9%) variants. LoH d-HWE was more likely in variants located within deletion polymorphisms (p < 0.001) and in variants with higher MAF-SD (p = 0.0077). GoH d-HWE was associated with low genotyping rate, with variants of insertion/deletion type and with high MAF (all at p < 0.001). In a sub-sample of 2,196 variants with genotyping rate >98%, LoH d-HWE was found in 29 (1.3%) variants, but no GoH d-HWE was detected. The findings of the non-random distribution of HWE-violating SNPs along the chromosome, the association with common deletion polymorphisms and indel-variant type, and the finding of excess heterozygotes in genomic regions that are prone to cross-hybridization were confirmed in a large sample of short variants from the 1,000 Genomes Project. Conclusions: We differentiated between two types of HWE-departure. GoH d-HWE was suggestive for genotyping error. LoH d-HWE, on the contrary, pointed to natural variabilities such as population substructure or common deletion polymorphisms.

Dataset Information

Fitting Proportional Odds Model to Case-Control data with Incorporating Hardy-Weinberg Equilibrium.

Publications

Fitting Proportional Odds Model to Case-Control data with Incorporating Hardy-Weinberg Equilibrium.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets