DNAprint Genomics (DNAG)

[mingwan0]

Here is an article that has been accepted for publication by the American Journal of Human Genetics. There is clearly growing interest in MALD:

Linkage Analysis of a Complex Disease through Use of Admixed Populations

Xiaofeng Zhu,1 Richard S. Cooper,1 and Robert C. Elston2

1Department of Preventive Medicine and Epidemiology, Loyola University Medical Center, Maywood, IL; and 2Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland

Received September 2, 2003; accepted for publication March 12, 2004; electronically published May 6, 2004.

Linkage disequilibrium arising from the recent admixture of genetically distinct populations can be potentially useful in mapping genes for complex diseases. McKeigue has proposed a method that conditions on parental admixture to detect linkage. We show that this method tests for linkage only under specific assumptions, such as equal admixture in the parental generation and admixture that occurs in a single generation. In practice, these assumptions are unlikely to hold for natural populations, resulting in an inflation of the type I error rate when testing for linkage by this method. In this article, we generalize McKeigue's approach of testing for linkage to allow two different admixture models: (1) intermixture admixture and (2) continuous gene flow. We calculate the sample size required for a genomewide search by this method under different disease models: multiplicative, additive, recessive, and dominant. Our results show that the sample size required to obtain 90% power to detect a putative mutant allele at a genomewide significance level of 5% can usually be achieved in practice if informative markers are available at a density of 2 cM.