Incorporating Hardy-Weinberg Equilibrium Law to Enhance the Association Strength for Ordinal Trait Genetic Study

doi:10.1111/ahg.12142

CSpace > 系统科学研究所

	Incorporating Hardy-Weinberg Equilibrium Law to Enhance the Association Strength for Ordinal Trait Genetic Study
	Zhang, Wei; Li, Qizhai
	2016-03-01
发表期刊	ANNALS OF HUMAN GENETICS
ISSN	0003-4800
卷号	80 期号:2 页码:102-112
摘要	The conventional method to examine whether genetic variants are associated with the ordinal traits is the proportional odds model. Such analyses are often conducted by assuming an additive genetic mode of inheritance. However, how the genetic variants influence the risk of occurrence of a disease is impossible to know in practice. Using an improper model might result in a low-power test, thus it reduces the probability of detecting the deleterious genetic markers. To address these concerns, we propose a two-phase procedure (TPP) for ordinal trait genetic studies. In the first phase, we used a linear combination to weight the Hardy-Weinberg equilibrium tests in case groups and formed an omnibus test to classify the genetic models. Then based on the chosen model, the corresponding score test was used to identify the associations. To control the false positive rate, we derived the joint distribution of the test used for selecting the genetic model and that used for identifying the associations. We also obtained the closed forms of two other robust tests, MAX3 and CHI2. Extensive computer simulations were carried out and the results showed that the true selection rates of genetic models are satisfactory and the proposed TPP is more robust than MAX3 and CHI2. Finally, we demonstrated the advantage of our proposed method by applying it to analyse the antibody reactivity to cyclic citrullinated peptides data.
关键词	Genetic model proportional odds model score test two-phase procedure association studies
DOI	10.1111/ahg.12142
语种	英语
资助项目	National Science Foundation of China[11371353] ; National Science Foundation of China[61134013] ; Strategic Priority Program of the Chinese Academy of Sciences[XDB13040600]
WOS研究方向	Genetics & Heredity
WOS类目	Genetics & Heredity
WOS记录号	WOS:000371626400003
出版者	WILEY-BLACKWELL
引用统计
文献类型	期刊论文
条目标识符	http://ir.amss.ac.cn/handle/2S8OKBNM/22202
专题	系统科学研究所
通讯作者	Li, Qizhai
作者单位	Chinese Acad Sci, Acad Math & Syst Sci, Key Lab Syst & Control, Beijing, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Wei,Li, Qizhai. Incorporating Hardy-Weinberg Equilibrium Law to Enhance the Association Strength for Ordinal Trait Genetic Study[J]. ANNALS OF HUMAN GENETICS,2016,80(2):102-112.
APA	Zhang, Wei,&Li, Qizhai.(2016).Incorporating Hardy-Weinberg Equilibrium Law to Enhance the Association Strength for Ordinal Trait Genetic Study.ANNALS OF HUMAN GENETICS,80(2),102-112.
MLA	Zhang, Wei,et al."Incorporating Hardy-Weinberg Equilibrium Law to Enhance the Association Strength for Ordinal Trait Genetic Study".ANNALS OF HUMAN GENETICS 80.2(2016):102-112.