Implications of the Co-Dominance Model for Hardy-Weinberg Testing in Genetic Association Studies.

IF 1.1 4区 生物学 Q4 GENETICS & HEREDITY Human Heredity Pub Date : 2024-03-02 DOI:10.1159/000537832
Stefan Wellek, Martina Mueller-Nurasyid, Konstantin Strauch
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Abstract

Introduction: The standard way of using tests for compatibility of genetic markers with the Hardy-Weinberg equilibrium (HWE) assumptionvas a means of quality control in genetic association studies (GAS) is to vcarry out this step of preliminary data analysis with the sample of non-diseased vindividuals only. We show that this strategy has no rational basis whenever the genotype--phenotype relation for avmarker under consideration satisfies the assumption of co-dominance.

Methods/results: The justification of this statement is the fact rigorously shown here that under co-dominance, the genotype distribution of a diallelic marker is in HWE among the controls if and only if the same holds true for the cases.

Conclusion: The major practical consequence of that theoretical result is that under the co-dominance model, testing for HWE should be done both for cases and controls aiming to establish the combined (intersection) hypothesis of compatibility of both underlying genotype distributions with the HWE assumption. A particularly useful procedure serving this purpose is obtained through applying the confidence-interval inclusion rule derived by Wellek, Goddard and Ziegler (Biom J. 2010; 52:253-270) to both samples separately and combining these two tests by means of the intersection-union principle.

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共显性模型对遗传关联研究中哈迪-温伯格测试的影响。
导言:在遗传关联研究(GAS)中,检验遗传标记是否符合哈代-温伯格平衡(HWE)假设的标准方法是,只对未患病个体样本进行初步数据分析。我们的研究表明,只要所研究的基因型与表型的关系满足共显性假设,这种策略就没有合理的依据:方法/结果:这一说法的依据是本文严格证明的事实,即在共显性条件下,当且仅当病例的基因型分布同样成立时,二重标记的基因型分布在对照组中处于 HWE 状态:该理论结果的主要实际结果是,在共显性模型下,应同时对病例和对照进行 HWE 检测,以建立两个基本基因型分布与 HWE 假设相容的组合(交叉)假设。Wellek, Goddard and Ziegler(Biom J. 2010; 52:253-270)得出的置信区间包含规则可分别应用于两个样本,并通过交集-联合原则将这两个检验结合起来。
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来源期刊
Human Heredity
Human Heredity 生物-遗传学
CiteScore
2.50
自引率
0.00%
发文量
12
审稿时长
>12 weeks
期刊介绍: Gathering original research reports and short communications from all over the world, ''Human Heredity'' is devoted to methodological and applied research on the genetics of human populations, association and linkage analysis, genetic mechanisms of disease, and new methods for statistical genetics, for example, analysis of rare variants and results from next generation sequencing. The value of this information to many branches of medicine is shown by the number of citations the journal receives in fields ranging from immunology and hematology to epidemiology and public health planning, and the fact that at least 50% of all ''Human Heredity'' papers are still cited more than 8 years after publication (according to ISI Journal Citation Reports). Special issues on methodological topics (such as ‘Consanguinity and Genomics’ in 2014; ‘Analyzing Rare Variants in Complex Diseases’ in 2012) or reviews of advances in particular fields (‘Genetic Diversity in European Populations: Evolutionary Evidence and Medical Implications’ in 2014; ‘Genes and the Environment in Obesity’ in 2013) are published every year. Renowned experts in the field are invited to contribute to these special issues.
期刊最新文献
Place of concordance-discordance model in evaluating NGS performance. Implications of the Co-Dominance Model for Hardy-Weinberg Testing in Genetic Association Studies. Joint Linkage and Association Analysis Using GENEHUNTER-MODSCORE with an Application to Familial Pancreatic Cancer. Investigation of Recessive Effects of Coding Variants on Common Clinical Phenotypes in Exome-Sequenced UK Biobank Participants. comorbidPGS: An R Package Assessing Shared Predisposition between Phenotypes Using Polygenic Scores.
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