Journal
EUROPEAN JOURNAL OF HUMAN GENETICS
Volume 9, Issue 4, Pages 301-306Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.ejhg.5200625
Keywords
TDT; RC-TDT; linkage disequilibrium; missing genotypes; censored traits; FBAT
Funding
- NIMH NIH HHS [MH59532-02, U01 MH46281, U01 MH46290, U01 MH46373] Funding Source: Medline
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With possibly incomplete nuclear families, the family based association test (FBAT) method allows one to evaluate any test statistic that can be expressed as the sum of products (covariance) between an arbitrary function of an offspring's genotype with an arbitrary function of the offspring's phenotype. We derive expressions needed to calculate the mean and variance of these test statistics under the null hypothesis of no linkage. To give some guidance on using the FBAT method, we present three simple data analysis strategies for different phenotypes: dichotomous (affection status), quantitative and censored (eg, the age of onset). We illustrate the approach by applying it to candidate gene data of the NIMH Alzheimer Disease Initiative. We show that the RC-TDT is equivalent to a special case of the FBAT method. This result allows us to generalise the RC-TDT to dominant, recessive and multi-allelic marker codings. Simulations compare the resulting FBAT tests to the RC-TDT and the S-TDT. The FBAT software is freely available.
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