scholarly journals A network algorithm for the X chromosomal exact test for Hardy-Weinberg equilibrium with multiple alleles

2020 ◽  
Author(s):  
Jan Graffelman ◽  
Leonardo Ortoleva
Keyword(s):  
Permutation Test ◽  
Statistical Methodology ◽  
Enumeration Algorithm ◽  
Test Procedures ◽  
Multiple Alleles ◽  
Exact Test ◽  
Weinberg Equilibrium ◽  
Network Algorithm ◽  
Hardy Weinberg Equilibrium ◽  
Chromosomal Variants

AbstractStatistical methodology for testing Hardy-Weinberg equilibrium at X chromosomal variants has recently experienced considerable development. Up to a few years ago, testing X chromosomal variants for equilibrium was basically done by applying autosomal test procedures to females only. At present, male alleles can be taken into account in asymptotic and exact test procedures for both the bi- and multiallelic case. However, current X chromosomal exact procedures for multiple alleles rely on a classical full enumeration algorithm and are computationally expensive, and in practice not feasible for more than three alleles. In this article we extend the autosomal network algorithm for exact Hardy-Weinberg testing with multiple alleles to the X chromosome, achieving considerable reduction in computation times for multiallelic variants with up to five alleles. The performance of the X-chromosomal network algorithm is assessed in a simulation study. Beyond four alleles, a permutation test is, in general, the more feasible approach. A detailed description of the algorithm is given and examples of X chromosomal indels and microsatellites are discussed.

scholarly journals Multi-allelic Exact tests for Hardy-Weinberg equilibrium that account for gender

2017 ◽  
Author(s):  
Jan Graffelman ◽  
Bruce Weir
Keyword(s):  
Permutation Test ◽  
Statistical Tests ◽  
Enumeration Algorithm ◽  
Test Procedures ◽  
Allelic Variants ◽  
Multiple Alleles ◽  
Exact Test ◽  
Weinberg Equilibrium ◽  
Hardy Weinberg Equilibrium ◽  
And Gender

Statistical tests for Hardy-Weinberg equilibrium are important elementary tools in genetic data analysis. X-chromosomal variants have long been tested by applying autosomal test procedures to females only, and gender is usually not considered when testing autosomal variants for equilibrium. Recently, we proposed specific X-chromosomal exact test procedures for bi-allelic variants that include the hemizygous males, as well as autosomal tests that consider gender. In this paper we present the extension of the previous work for variants with multiple alleles. A full enumeration algorithm is used for the exact calculations of tri-allelic variants. For variants with many alternate alleles we use a permutation test. Some empirical examples with data from the 1000 genomes project are discussed.

scholarly journals ABCB1 variants C3435T and T129C are not associated with colorectal cancer risk

2019 ◽  
Vol 19 (3) ◽  
pp. 2476-2483 ◽  
Author(s):  
Areej M Al Qahtani ◽  
Ayat B Al-Ghafari ◽  
Huda A Al Doghaither ◽  
Anas H Alzahrani ◽  
Ulfat M Omar ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Saudi Arabia ◽  
Goodness Of Fit ◽  
Allele Frequencies ◽  
Genotype Distribution ◽  
Exact Test ◽  
Weinberg Equilibrium ◽  
Pcr Rflp ◽  
Hardy Weinberg Equilibrium ◽  
And Control

Background: Colorectal cancer (CRC) is one of the most prevalent cancers in Saudi Arabia that is highly characterized with poor survival rate and advanced metastasis. Many studies contribute this poor outcome to the expression of ABC transporters on the surface of cancer cells.Objectives: In this study, two ABCB1 variants, C3435T and T129C, were examined to evaluate their contribution to CRC risk.Methods: 125 subjects (62 CRC patients and 63 healthy controls) were involved. The DNA was isolated and analyzed with PCR-RFLP to determine the different genotypes. The hardy-Weinberg equilibrium was performed to determine genotype distribution and allele frequencies. Fisher’s exact test (two-tailed) was used to compare allele frequencies between patients and control subjects. Results: The study showed that for SNP C3435T, the population of both CRC patients and controls were out of Hardy-Weinberg equilibrium. Genotype distribution for CRC patients was (Goodness of fit χ2 = 20, df= 1, P≤0.05), whereas, for the controls the genotype distribution was (Goodness of fit χ2 = 21, df =1, P ≤0.05). For SNP T129C, all subjects showed normal (TT) genotype.Conclusion: There was no significant association between ABCB1 3435C>T and 129T>C polymorphisms with CRC risk.Keywords: Colorectal cancer, ABCB1 gene, SNP C3435T, SNP T129C, PCR-RFLP, Saudi Arabia.

scholarly journals New Equivalence Tests for Hardy–Weinberg Equilibrium and Multiple Alleles

Stats ◽  
2020 ◽  
Vol 3 (1) ◽  
pp. 34-39
Author(s):  
Vladimir Ostrovski
Keyword(s):  
Bootstrap Method ◽  
Real Data ◽  
Data Sets ◽  
Test Statistics ◽  
Finite Sample ◽  
Multiple Alleles ◽  
Weinberg Equilibrium ◽  
Equivalence Tests ◽  
Hardy Weinberg Equilibrium ◽  
The Bootstrap Method

We consider testing equivalence to Hardy–Weinberg Equilibrium in case of multiple alleles. Two different test statistics are proposed for this test problem. The asymptotic distribution of the test statistics is derived. The corresponding tests can be carried out using asymptotic approximation. Alternatively, the variance of the test statistics can be estimated by the bootstrap method. The proposed tests are applied to three real data sets. The finite sample performance of the tests is studied by simulations, which are inspired by the real data sets.

An Unconditional Exact Test for the Hardy-Weinberg Equilibrium Law: Sample-Space Ordering Using the Bayes Factor

Genetics ◽  
2001 ◽  
Vol 158 (2) ◽  
pp. 875-883
Author(s):  
Luis E Montoya-Delgado ◽  
Telba Z Irony ◽  
Carlos A de B. Pereira ◽  
Martin R Whittle
Keyword(s):  
Bayes Factor ◽  
Statistical Tests ◽  
Sample Space ◽  
P Value ◽  
Type I ◽  
Weighted Likelihood ◽  
Asymptotic Results ◽  
Exact Test ◽  
Weinberg Equilibrium ◽  
Hardy Weinberg Equilibrium

Abstract Much forensic inference based upon DNA evidence is made assuming that the Hardy-Weinberg equilibrium (HWE) is valid for the genetic loci being used. Several statistical tests to detect and measure deviation from HWE have been devised, each having advantages and limitations. The limitations become more obvious when testing for deviation within multiallelic DNA loci is attempted. Here we present an exact test for HWE in the biallelic case, based on the ratio of weighted likelihoods under the null and alternative hypotheses, the Bayes factor. This test does not depend on asymptotic results and minimizes a linear combination of type I and type II errors. By ordering the sample space using the Bayes factor, we also define a significance (evidence) index, P value, using the weighted likelihood under the null hypothesis. We compare it to the conditional exact test for the case of sample size n = 10. Using the idea under the method of χ2 partition, the test is used sequentially to test equilibrium in the multiple allele case and then applied to two short tandem repeat loci, using a real Caucasian data bank, showing its usefulness.

scholarly journals Robust, flexible, and scalable tests for Hardy-Weinberg Equilibrium across diverse ancestries

2020 ◽  
Author(s):  
Alan M. Kwong ◽  
Thomas W. Blackwell ◽  
Jonathon LeFaive ◽  
Mariza de Andrade ◽  
John Barnard ◽  
...  
Keyword(s):  
Population Structure ◽  
Statistical Power ◽  
Software Tool ◽  
Population Heterogeneity ◽  
Alternative Methods ◽  
Real Sequence ◽  
Exact Test ◽  
Weinberg Equilibrium ◽  
Hardy Weinberg Equilibrium ◽  
The Impact

ABSTRACTTraditional Hardy-Weinberg equilibrium (HWE) tests (the χ2 test and the exact test) have long been used as a metric for evaluating genotype quality, as technical artifacts leading to incorrect genotype calls often can be identified as deviations from HWE. However, in datasets comprised of individuals from diverse ancestries, HWE can be violated even without genotyping error, complicating the use of HWE testing to assess genotype data quality. In this manuscript, we present the Robust Unified Test for HWE (RUTH) to test for HWE while accounting for population structure and genotype uncertainty, and evaluate the impact of population heterogeneity and genotype uncertainty on the standard HWE tests and alternative methods using simulated and real sequence datasets. Our results demonstrate that ignoring population structure or genotype uncertainty in HWE tests can inflate false positive rates by many orders of magnitude. Our evaluations demonstrate different tradeoffs between false positives and statistical power across the methods, with RUTH consistently amongst the best across all evaluations. RUTH is implemented as a practical and scalable software tool to rapidly perform HWE tests across millions of markers and hundreds of thousands of individuals while supporting standard VCF/BCF formats. RUTH is publicly available at https://www.github.com/statgen/ruth.

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