Statistical models for genetics data are often surprisingly challenging, and often require advanced and new statistical methods. This project investigates two such areas: extension of a scheme for estimation of linkage from transmission/disequilibrium data, and a new comprehensive approach to genome scans. This project is the first to estimate TDT linkage and association model parameters from data collected jointly from both parents and all affected children. Using a series of realistic simulations we show that our TDT estimation methods are essentially as powerful and robust as the classical TDT, while our confidence intervals for linkage and association provide significantly new useful information. 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. We have recently extended the approach to sampling plans that use allele transmision data from both parents. Simulations confirm that this approach give increased power to detecting association and linkage (separately).[1] J.E.Bailey-Wilson, J.D.Malley et al.: Comparison of Novel and Existing Methods for Detection of Linkage Disequilibrium Using Parent-Child Trios in GAW 12 Genetic Isolate Simulated Data. Genetic Epidemiology, 21(Suppl 1): S378-S383 (2001). [2] Estimation of Linkage and Association from Allele Transmission Data, (in revision) Biometrical Journal (2002).The genome scan technology involves the use of importance sampling to accurately estimate the level of significance for multiple testing using many markers, several thousand at a time. It is shown to be significantly more efficient than naive Monte Carlo testing, and handles the case of unequally spaced markers. Previous work in this area used large deivation probabilistic methods that did not address the case of unequally spaced markers. Also, the importance sampling approach extends to multiple testing in Hardy-Weinberg problems, multiple allele TDT testing, and many other mutiple testing problems in genetics. [3] Results were presented as an invited talk at the Intl. Gen. Epi. Soc. meeting in Garmisch-Partenkirschen, Germany (Sept. 2001). [4] Malley, Naiman and Bailey-Wilson (2002) Comprehensive Method for Genome Scanning. (in revision) Human Heredity.

Agency
National Institute of Health (NIH)
Institute
Center for Information Technology (CIT)
Type
Intramural Research (Z01)
Project #
1Z01CT000268-04
Application #
6725205
Study Section
(MSCL)
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2002
Total Cost
Indirect Cost
Name
Computer Research and Technology
Department
Type
DUNS #
City
State
Country
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
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
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; 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

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