Statistical models for genetics data are often surprisingly challenging, and often requires advanced and new statistical methods. This project investigates a simple, widely used test (the TDT) for detecting association and/or linkage from parent child data. The transmission/disequilibrium test (TDT) has widespread use in statistical genetics, as it does not make any assumptions regarding mode of inheritance, penetrance rates, marker or disease allele frequencies or population stratification. It is understood to have high power for detecting association and/or linkage, and is very simple to apply. However, it does not directly estimate any of the underlying parameters in the allele transmission probability model, nor provide for follow-up estimation when the null model of no association or linkage as been rejected. This project is the first to estimate TDT model parameters, thereby solving a long-standing problem in statistical genetics. We introduce a new parametrization of the model, and show that the TDT has in fact rather low power over a broad range of the parameter space. Using a series of realistic simulations we show that our methods are essentially as powerful and robust as the classical TDT, while our confidence intervals for linkage and association provide significantly new useful information. Using a second new parameterization we introduce a likelihood ratio test and show that it is uniformaly more powerful than the TDT when testing for linkage. All results were thorougly tested using a series of realistic simulations and models, and demonstrated that our estimation methods are a valuable contribution to practical genetics data analysis.[1] Malley, Redner, Severini, Badner, Bailey-Wilson, Pajevic (2000). Estimation of Association and Linkage from Transmission/disequilibrium (TDT) Data. Under review at the American Journal of Human Genetics.

National Institute of Health (NIH)
Center for Information Technology (CIT)
Intramural Research (Z01)
Project #
Application #
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Computer Research and Technology
United States
Zip Code
Konig, I R; Malley, J D; Weimar, C et al. (2007) Practical experiences on the necessity of external validation. Stat Med 26:5499-511
Gupta, Vaijayanti; Parisi, Michael; Sturgill, David et al. (2006) Global analysis of X-chromosome dosage compensation. J Biol 5:3
Stojanov, Silvia; Hoffmann, Florian; Kery, Anja et al. (2006) Cytokine profile in PFAPA syndrome suggests continuous inflammation and reduced anti-inflammatory response. Eur Cytokine Netw 17:90-7
O'Hanlon, Terrance P; Rider, Lisa G; Mamyrova, Gulnara et al. (2006) HLA polymorphisms in African Americans with idiopathic inflammatory myopathy: allelic profiles distinguish patients with different clinical phenotypes and myositis autoantibodies. Arthritis Rheum 54:3670-81
Mamyrova, Gulnara; O'Hanlon, Terrance P; Monroe, Jason B et al. (2006) Immunogenetic risk and protective factors for juvenile dermatomyositis in Caucasians. Arthritis Rheum 54:3979-87
O'Hanlon, Terrance P; Carrick, Danielle Mercatante; Targoff, Ira N et al. (2006) Immunogenetic risk and protective factors for the idiopathic inflammatory myopathies: distinct HLA-A, -B, -Cw, -DRB1, and -DQA1 allelic profiles distinguish European American patients with different myositis autoantibodies. Medicine (Baltimore) 85:111-27
O'Hanlon, Terrance P; Carrick, Danielle Mercatante; Arnett, Frank C et al. (2005) Immunogenetic risk and protective factors for the idiopathic inflammatory myopathies: distinct HLA-A, -B, -Cw, -DRB1 and -DQA1 allelic profiles and motifs define clinicopathologic groups in caucasians. Medicine (Baltimore) 84:338-49
Parisi, Michael; Nuttall, Rachel; Edwards, Pamela et al. (2004) A survey of ovary-, testis-, and soma-biased gene expression in Drosophila melanogaster adults. Genome Biol 5:R40
O'Hanlon, Terrance; Koneru, Bhanu; Bayat, Elham et al. (2004) Immunogenetic differences between Caucasian women with and those without silicone implants in whom myositis develops. Arthritis Rheum 50:3646-50
Jerebko, Anna K; Summers, Ronald M; Malley, James D et al. (2003) Computer-assisted detection of colonic polyps with CT colonography using neural networks and binary classification trees. Med Phys 30:52-60

Showing the most recent 10 out of 24 publications