Biostatistics Advance Access originally published online on May 22, 2007
Biostatistics 2008 9(1):114-127; doi:10.1093/biostatistics/kxm016
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A score test for linkage analysis of ordinal traits based on IBD sharing
Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL 35294, USA rfeng{at}ms.soph.uab.edu
Department of Epidemiology and Public Health, Yale University, New Haven, CT 06520, USA and Jiangxi Normal University, Nanchang, People's Republic of China
* To whom correspondence should be addressed.
Statistical methods for linkage analysis are well established for both binary and quantitative traits. However, numerous diseases including cancer and psychiatric disorders are rated on discrete ordinal scales. To analyze pedigree data with ordinal traits, we recently proposed a latent variable model which has higher power to detect linkage using ordinal traits than methods using the dichotomized traits. The challenge with the latent variable model is that the likelihood is usually very complicated, and as a result, the computation of the likelihood ratio statistic is too intensive for large pedigrees. In this paper, we derive a computationally efficient score statistic based on the identity-by-decent sharing information between relatives. Using simulation studies, we examined the asymptotic distribution of the test statistic and the power of our proposed test under various levels of heritability. We compared the computing time as well as power of the score test with the likelihood ratio test. We then applied our method for the Collaborative Study on the Genetics of Alcoholism and performed a genome scan to map susceptibility genes for alcohol dependence. We found a strong linkage signal on chromosome 4.
Keywords: COGA; IBD; Linkage analysis; Ordinal traits; Score test
Received October 27, 2006; revised March 27, 2007; accepted for publication April 11, 2007.