FBAT

Introduction

FBAT implements a broad class of Family Based Association Tests, adjusted for population admixture. FBAT features include:

· Uses data from nuclear families, sibships, pedigrees, or any combination; provides unbiased tests with or without founder genotypes.

· Analyzes dichotomous, measured, or time-to-onset traits and multiple traits; trait definition can be optimized.

· Analyzes markers on the x-chromosome with same options as autosomal marker analysis

· Offers bi-allelic and multi-allelic tests of association using standard genetic models (additive, dominant, recessive or genotype).

· Offers large sample and Monte-Carlo exact tests of the null hypothesis: no linkage and no association; offers large sample test of H0: no association.

· Estimates allele frequencies; checks Mendelian consistency.

· Tests multiple markers using haplotypes; estimates haplotype frequencies and linkage disequilibrium between pairs of markers.

· Offers three multi-marker tests for testing multiple markers simultaneously, without resolving phase or assuming no recombination.

· Offers two multiple trait tests.

· Interactive and command driven program using standard pedigree data files; phenotype file is optional.

Download Software

FBAT 2.0.4 beta is available for the following platforms:

FBAT is available for the following platforms:

A copy of older version (V1.7.3) of FBAT is also available for the following platforms:

Documentation for FBAT is included in the above packages. In addition, the following two documents for FBAT are also available online. Please read the user's manual if you are not sure how to uncompress the archives.

Family-Based association tests and the FBAT-Toolkit 2.0.4 Beta: A word documentation describing the new feature for analyzing rare variants in version 2.0.4, the basis of the FBAT/PBAT tests and a user manual for FBAT.
Family-Based association tests and the FBAT-Toolkit: A word documentation describing the basis of the FBAT/PBAT tests and a user manual for FBAT.
A tour of FBAT (MS Word file): A tutorial for the new FBAT user with four sample data sets.
Technical report1 (postsrcipt file): "The family based association test method: computing means and variances for general statistics."
Technical report2 (pdf file): "Family based tests for associating haplotypes with general phenotype data."

References

*Main methods papers relating to FBAT

Xiao Ding, Christoph Lange, Xin Xu, Nan Laird (2007) Family-based association tests with longitudinal measurements: a comparison of several approaches. Submitted.

Horvath S, Xu X and Laird N (2001) The family based association test method: strategies for studying general genotype-phenotype associations. Euro J Hum Gen 9: 301-306.

Horvath, S, Xu, X, Lake, S, Silverman, E, Weiss, S, and Laird, N (2004) Tests for Associating Haplotypes with General Phenotype Data: Application to Asthma Genetics. Gen Epi 26: 61-69.

Laird NM, Horvath S and Xu X (2000) Implementing a unified approach to family based tests of association. Genetic Epi 19(Suppl 1): S36-S42.

Laird NM, Kraft P, van Steen, K and Lange, C.(2005) Testing for association in genetic studies in E. Silverman et al., Eds, Hodder Arnold: Boston, MA, 27-46.

Lake S, Blacker, and Laird N (2001) Family based tests in the presence of association. Amer J Hum Gen 67:1515-1525.

Lange C, Silverman EK, Xu X, Weiss ST, Laird NM (2003) A multivariate family-based association test using generalized estimating equations: FBAT-GEE Biostatistics 4:195-306.

Lunetta KL, Farone SV, Biederman J, and Laird NM (2000) Family based tests of association and linkage using unaffected sibs, covariates and interactions. Amer J Hum Gen 66: 605-614.

Rabinowitz D and Laird NM (2000) A unified approach to adjusting association tests for population admixture with arbitrary pedigree structure and arbitrary missing marker information. Human Heredity 504:227-233.

Rakovski, C, Xu, X, Lazarus, R and Laird NM (2007) A new multi-marker test for family based association studies. Genet Epidemiol, 31(1): p. 9-17.

Xu, X, Rakovski, C. and Laird, NM. (2008). “An Efficient Family-Based Association Test using Multiple Markers” To appear, Human Heridity.

*Other methods papers related to FBAT and PBAT

Horvath S, Laird NM, Knapp M (2000) The transmission/disequilibrium test and parental genotype reconstruction for X-chromosomal markers. Amer J Human Gen 66:1161¨C1167.

Horvath S, Wei E, Xu X, Palmer L, and Baur M. (2001) Family-based association test method I: Age of onset traits and covariates. Genetic Epi Suppl (GAW 2000) 9:36-42.

Lake S and Laird N (2004) Tests of gene-environment interaction for case-parent triads with general environmental exposures. Ann Hum Genet 68:55-64.

Lange C, Blacker D and Laird NM (2003) Family-based association tests for survival and time-to-onset analysis. Statist Med 22: 179-189.

Lange C, DeMeo D and Laird NM (2002) Power calculations for a general class of family-based association tests: Quantitative traits. Am J Hum Genet 71:575-584.

Lange C and Laird NM (2002) Power calculations for a general class of family-based association tests: Dichotomous traits. Am J Hum Genet 67:575-584.

Lange C and Laird NM (2002) On a general class of conditional tests for family based association studies in genetics: The asymptotic distribution, the conditional power, and optimality considerations. Gen Epi 23:1-16

Lange C, DeMeo D, Silverman E, Weiss S and Laird NM (2004) PBAT: tools for family-based association studies Am J Hum Genet 74:367-9.

Lange C, DeMeo D, Silverman E, Weiss S and Laird NM (2003) Using the noninformative families in family-based association tests: a powerful new testing strategy. Am J Hum Genet 73:801-11.

Lange C, Lyon H, DeMeo D, Raby BA, Silverman E and Weiss S (2003) A new powerful non-parametric two-stage approach for testing multiple phenotypes in family-based association studies. Human Heredity 56:10-17.

Van Steen, K, Laird, NM, Lange,C et al., Genomic screening and replication using the same data set in family-based studies. Nat Genet. 37:683-91.

Yang Q, Xu X and Laird NM (2003) Power Evaluation for Family-Based Tests of Association with Incomplete Parental Genotypes. Genetics 164: 399-406.

*Reference for the SDT

Horvath S and Laird NM (1998) A Discordant sibship test for disequilibrium and linkage: No need for parental data. Amer J Hum Gen 63: 1886-97.

*Applications

DeMeo DM, Lange C, Silverman EK, Senter JM, Drazen JM, Barth MJ, Laird N, and Weiss ST. (2002) Univariate and multivariate family based analysis of the ARG130GLN polymorphism of the il13 gene in the childhood asthma management program. Genetic Epi 23:335-348.

Lyon H, Lange C, Silverman EK, Senter JM, Drazen JM, Barth MJ, Laird N, and Weiss ST. (2004) Univariate and multivariate family based analysis of the il10 gene in the childhood asthma management program. Genetic Epi 26:155-165.

Saunders AJ, Bertram L, Mullin K, Sampson AJ, Latifzai K, Basu S, Jones J, Kinney D, MacKenzie-Ingano L, Yu S, Albert MS, Moscarillo TJ, Go RC, Bassett SS, Daly MJ, Laird NM, Wang X, Velicelebi G, Wagner SL, Becker DK, Tanzi RE, Blacker D. (2003) Genetic association of Alzheimer disease with multiple polymorphisms in alpha-2-macroblobulin. Hum Mol Genet 12:2765-76.

Silverman EK, Kwiatkowski DJ, Sylvia JS, Lazarus R, Drazen JM, Lange C, Laird NM, Weiss ST. (2003) Family-based association analysis of beta2-adrenergic receptor polymorphisms in the childhood asthma management program. J Allergy Clin Immunol. 112:870-6.

Smoller JW, Rosenbaum JF, Biederman J, Kennedy J, Dai D, Racette SR, Laird NM, Kagan J, Snidman N, Hirshfeld-Becker D, Tsuang MT, Sklar PB, Slaugenhaupt SA. (2003) Association of a genetic marker at the corticotropin-releasing hormone locus with behavioral inhibition. Biol Psychiatry 54: 1376-81.

Smoller JW, Yamaki LH, Faterness JA, Biederman J, Racette S, Laird NM et al., (2005) The corticotrophin-releasing hormone gene and behavioral inhibition in children at risk for panic disorder. Biol Psychiatry 57:1485-92.