Am J Epidemiol 2003; 158:397-400.
Copyright © 2003 by Johns
Hopkins Bloomberg School of Public Health
ORIGINAL CONTRIBUTIONS |
Searching for Disease-Susceptibility Loci by Testing for Hardy-Weinberg Disequilibrium in a Gene Bank of Affected Individuals
From the Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan.
The future of genetic studies of complex human diseases will rely more and more on the epidemiologic association paradigm. The author proposes to scan the genome for disease-susceptibility gene(s) by testing for deviation from Hardy-Weinberg equilibrium in a gene bank of affected individuals. A power formula is presented, which is very accurate as revealed by Monte Carlo simulations. If the disease-susceptibility gene is recessive with an allele frequency of 
0.5 or dominant with an allele frequency of 
0.5, the number of subjects needed by the present method is smaller than that needed by using a case-parents design (using either the transmission/disequilibrium test or the 2-df likelihood ratio test). However, the method cannot detect genes with a multiplicative mode of inheritance, and the validity of the method relies on the assumption that the source population from which the cases arise is in Hardy-Weinberg equilibrium. Thus, it is prone to produce false positive and false negative results. Nevertheless, the method enables rapid gene hunting in an existing gene bank of affected individuals with no extra effort beyond simple calculations.
disease susceptibility; epidemiologic methods; gene library; genetics; genome; Hardy-Weinberg equilibrium; Monte Carlo method; polymorphism, single nucleotide
Abbreviations: Abbreviation: HWT, Hardy-Weinberg disequilibrium test.
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