Two important aspects of statistical genetics research are development of new methods and application of such methods to datasets. In many cases, statistical research focuses on development, and ignores delivery of the methods to the potential users. Recently the P1 and colleagues have proposed a conceptual basis for unifying """"""""model-based"""""""" and """"""""model-free"""""""" linkage and linkage disequilibrium (LD) analysis for genetic epidemiology studies of dichotomous traits. The approach has been used in practice by the PT, in numerous practical applications, but can be very cumbersome to apply using the existing software packages, making them inaccessible to the broader community of scientists who might wish to apply them in practice. To this end, as part of this application, it is proposed to develop and distribute software which can automatically perform these analyses in a simple and straightforward manner. By making powerful techniques accessible (at least in their most general form) to those without substantial statistical and computing training, an important service will be provided to the community of gene mappers, and those trying to detect linkage and/or LD in their own datasets. Furthermore, such methods can allow for post-hoc analysis of errors in genotyping, errors in genetic marker maps, and errors in the assumed genotype-phenotype relationship at the locus under study. Joint analysis of multiple genes will also be incorporated in the software, through the use of statistical models recently described by the PT. Additionally, software packages will be developed for simulation of more realistic datasets, allowing investigators to more accurately predict the chance for successful mapping within a specified study design. Software to simulate the evolution of gene sequences in populations will be made available, such that users can evaluate the effects of different assumptions about population parameters on allelic complexity, gene diversity, and levels of LD, and software will be developed for simulation and ascertainment of pedigrees from populations, conditional on models of joint genetic and environmental etiology of common traits (qualitative and quantitative). These programs will be distributed as part of the expanded ANALYZE software package to be developed in this proposed project.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH063749-02
Application #
6539287
Study Section
Mammalian Genetics Study Section (MGN)
Program Officer
Moldin, Steven Owen
Project Start
2001-07-10
Project End
2006-06-30
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
2
Fiscal Year
2002
Total Cost
$367,875
Indirect Cost
Name
Columbia University (N.Y.)
Department
Psychiatry
Type
Schools of Medicine
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032
Hiekkalinna, Tero; Göring, Harald H H; Lambert, Brian et al. (2012) On the statistical properties of family-based association tests in datasets containing both pedigrees and unrelated case-control samples. Eur J Hum Genet 20:217-23
Weiss, Kenneth M; Buchanan, Anne V (2011) Is life law-like? Genetics 188:761-71
Weiss, Kenneth M; Buchanan, Anne V; Lambert, Brian W (2011) The Red Queen and her king: cooperation at all levels of life. Am J Phys Anthropol 146 Suppl 53:3-18
Hiekkalinna, Tero; Schäffer, Alejandro A; Lambert, Brian et al. (2011) PSEUDOMARKER: a powerful program for joint linkage and/or linkage disequilibrium analysis on mixtures of singletons and related individuals. Hum Hered 71:256-66
Weiss, Kenneth M; Lambert, Brian W (2011) When the time seems ripe: eugenics, the annals, and the subtle persistence of typological thinking. Ann Hum Genet 75:334-43
Weiss, Kenneth M; Long, Jeffrey C (2009) Non-Darwinian estimation: my ancestors, my genes' ancestors. Genome Res 19:703-10
Paunio, Tiina; Arajärvi, Ritva; Terwilliger, Joseph D et al. (2009) Linkage analysis of schizophrenia controlling for population substructure. Am J Med Genet B Neuropsychiatr Genet 150B:827-35
Lambert, Brian W; Terwilliger, Joseph D; Weiss, Kenneth M (2008) ForSim: a tool for exploring the genetic architecture of complex traits with controlled truth. Bioinformatics 24:1821-2
Weiss, Kenneth M (2008) Tilting at quixotic trait loci (QTL): an evolutionary perspective on genetic causation. Genetics 179:1741-56
Haghighi, F; Bach-Mizrachi, H; Huang, Y Y et al. (2008) Genetic architecture of the human tryptophan hydroxylase 2 Gene: existence of neural isoforms and relevance for major depression. Mol Psychiatry 13:813-20

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