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The Sib TDT Adjusted For Age Of Disease Onset
Author(s) -
Ghosh Saurabh,
Reich Theodore
Publication year - 2004
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1046/j.1529-8817.2004.00090.x
Subject(s) - covariate , statistic , linkage (software) , proportional hazards model , allele , disease , genetics , statistics , age of onset , biology , medicine , mathematics , gene
Summary Since the Sib‐TDT (Spielman & Ewens, 1998) ignores age of disease onset, there could be loss of power in detecting linkage. In this article, we propose an adjustment for age of onset using the Cox Proportional Hazard Model (Cox, 1972) with the marker allele as a covariate. The test statistic for linkage is identical to the traditional Sib‐TDT. Monte‐Carlo simulations are performed under different disease models to assess the increase in power of the age‐adjusted Sib‐TDT compared to the traditional Sib‐TDT. We extend our method to multiallelic markers. An application using data on Alzheimer's Disease is also presented.