Fan Xia1, Ji-Yuan Zhou, Wing Kam Fung. 1. Department of Statistics and Actuarial Science, The University of Hong Kong, Hong Kong.
Abstract
MOTIVATION: For a diallelic marker locus, the transmission disequilibrium test (TDT) is a simple and powerful design for genetic studies. The TDT was originally proposed for use in families with both parents available (complete nuclear families) and has further been extended to 1-TDT for use in families with only one of the parents available (incomplete nuclear families). Currently, the increasing interest of the influence of parental imprinting on heritability indicates the importance of incorporating imprinting effects into the mapping of association variants. RESULTS: In this article, we extend the TDT-type statistics to incorporate imprinting effects and develop a series of new test statistics in a general two-stage framework for association studies. Our test statistics enjoy the nature of family-based designs that need no assumption of Hardy-Weinberg equilibrium. Also, the proposed methods accommodate complete and incomplete nuclear families with one or more affected children. In the simulation study, we verify the validity of the proposed test statistics under various scenarios, and compare the powers of the proposed statistics with some existing test statistics. It is shown that our methods greatly improve the power for detecting association in the presence of imprinting effects. We further demonstrate the advantage of our methods by the application of the proposed test statistics to a rheumatoid arthritis dataset. CONTACT: wingfung@hku.hk SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
MOTIVATION: For a diallelic marker locus, the transmission disequilibrium test (TDT) is a simple and powerful design for genetic studies. The TDT was originally proposed for use in families with both parents available (complete nuclear families) and has further been extended to 1-TDT for use in families with only one of the parents available (incomplete nuclear families). Currently, the increasing interest of the influence of parental imprinting on heritability indicates the importance of incorporating imprinting effects into the mapping of association variants. RESULTS: In this article, we extend the TDT-type statistics to incorporate imprinting effects and develop a series of new test statistics in a general two-stage framework for association studies. Our test statistics enjoy the nature of family-based designs that need no assumption of Hardy-Weinberg equilibrium. Also, the proposed methods accommodate complete and incomplete nuclear families with one or more affected children. In the simulation study, we verify the validity of the proposed test statistics under various scenarios, and compare the powers of the proposed statistics with some existing test statistics. It is shown that our methods greatly improve the power for detecting association in the presence of imprinting effects. We further demonstrate the advantage of our methods by the application of the proposed test statistics to a rheumatoid arthritis dataset. CONTACT: wingfung@hku.hk SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Authors: Sally John; Neil Shephard; Guoying Liu; Eleftheria Zeggini; Manqiu Cao; Wenwei Chen; Nisha Vasavda; Tracy Mills; Anne Barton; Anne Hinks; Steve Eyre; Keith W Jones; William Ollier; Alan Silman; Neil Gibson; Jane Worthington; Giulia C Kennedy Journal: Am J Hum Genet Date: 2004-05-20 Impact factor: 11.025
Authors: Christopher I Amos; Wei Vivien Chen; Elaine Remmers; Katherine A Siminovitch; Michael F Seldin; Lindsey A Criswell; Annette T Lee; Sally John; Neil D Shephard; Jane Worthington; Francois Cornelis; Robert M Plenge; Ann B Begovich; Thomas D Dyer; Daniel L Kastner; Peter K Gregersen Journal: BMC Proc Date: 2007-12-18