A major project of this section is the development of new statistical genetics methodology as prompted by the needs of our applied studies. This year Dr. Bailey-Wilson worked on development of several new methods. We have continued our collaboration with Dr. Silvano Presciuttini from the University of Pisa, on the development of simplified, approximate and stepwise procedures for using genetic markers to differentiate siblings and other types of relative pairs from unrelated individuals. This methodology has applications in linkage analysis and in forensics. This collaboration has also initiated a new project, development of better methods for predicting mutation carrier status for BRCA1 in Italian families and a paper has been published this year on this work. The third project, in collaboration with Dr. Jim Malley at CIT, NIH, is the development of a new method for family based association tests that appears considerably more powerful than the TDT but more robust to false positives than is case-control association. Extensive simulation studies have been performed to test the performance of this method. Two papers demonstrating the properties of this methods were recently published. The fourth project, also in collaboration with Dr. Malley and with Dr. Dan Naiman of Johns Hopkins University (on sabbatical at NHGRI with Dr. Bailey-Wilson), is an application of less conservative methods of correcting for multiple testing in human genetics analysis. This method has been applied to Genetic Analysis Workshop data and a paper was published this fiscal year. A new project to develop propensity scores in linkage analyses as a method for inclusion of covariate effects has been initiated in conjunction with Betty Doan and Yin Yao. This method appears promising in that it is generally more powerful than including the covariates directly into the model, and does not have strongly inflated Type I error rates. Two manuscripts have been submitted. Finally, work is being done in this section to improve upon the computer implementation of various existing analysis methods. These projects are ongoing.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Intramural Research (Z01)
Project #
1Z01HG000153-06
Application #
6988648
Study Section
(IDRB)
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2004
Total Cost
Indirect Cost
Name
Human Genome Research
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Holzinger, Emily R; Verma, Shefali S; Moore, Carrie B et al. (2017) Discovery and replication of SNP-SNP interactions for quantitative lipid traits in over 60,000 individuals. BioData Min 10:25
Kim, Yoonhee; Doan, Betty Q; Duggal, Priya et al. (2007) Normalization of microarray expression data using within-pedigree pool and its effect on linkage analysis. BMC Proc 1 Suppl 1:S152
NCI-NHGRI Working Group on Replication in Association Studies; Chanock, Stephen J; Manolio, Teri et al. (2007) Replicating genotype-phenotype associations. Nature 447:655-60
Mandal, Diptasri M; Sorant, Alexa J M; Atwood, Larry D et al. (2006) Allele frequency misspecification: effect on power and Type I error of model-dependent linkage analysis of quantitative traits under random ascertainment. BMC Genet 7:21
Manolio, Teri A; Bailey-Wilson, Joan E; Collins, Francis S (2006) Genes, environment and the value of prospective cohort studies. Nat Rev Genet 7:812-20
Marroni, F; Pichler, I; De Grandi, A et al. (2006) Population isolates in South Tyrol and their value for genetic dissection of complex diseases. Ann Hum Genet 70:812-21
Gillanders, E M; Pearson, J V; Sorant, A J M et al. (2006) The value of molecular haplotypes in a family-based linkage study. Am J Hum Genet 79:458-68
Doan, Betty Q; Sorant, Alexa J M; Frangakis, Constantine E et al. (2006) Covariate-based linkage analysis: application of a propensity score as the single covariate consistently improves power to detect linkage. Eur J Hum Genet 14:1018-26
Doan, Betty Q; Frangakis, Constantine E; Shugart, Yin Y et al. (2005) Application of the propensity score in a covariate-based linkage analysis of the Collaborative Study on the Genetics of Alcoholism. BMC Genet 6 Suppl 1:S33
Bailey-Wilson, Joan; Almasy, Laura; de Andrade, Mariza et al. (2005) Genetic Analysis Workshop 14: microsatellite and single-nucleotide polymorphism marker loci for genome-wide scans. BMC Genet 6 Suppl 1:S1

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