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• W2615706473 abstract "We read with interest your approved guidance on the key issues which should be considered in preparing a genetic association study to be acceptable for publication in Thorax .1,2 While we agree with several points in this guidance, other points we consider to be exaggerated or, at best, controversial. We note that, in the eight genetic association studies published in Thorax since 2004, some of them do not conform to this guidance with regard to population size, number of polymorphisms studied, and their functionality. This is seen clearly in the latest published association study by Yarden and colleagues3 who examined four polymorphisms in the TNFα gene in patients with cystic fibrosis. Three of the studied polymorphisms were without functional information; no assessment of linkage disequilibrium, haplotype analysis or correction for multiple comparisons had been performed; and the population size—even after pooling the two different ethnic groups—showed that the study was underpowered.With regard to the population size required in your guidance, the numbers in table 1 are too high (regardless of the typing error that caused the cases required for minor allele frequencies of 0.2 and 0.4 to be reversed). The reason for this is the unusual use of 90% power instead of the widely applied 80%. In fact, 80% power is the default for the online genetic power calculator you yourself provided in your editorial. Using this default of 80%, much smaller numbers of cases could be obtained and considered as having enough power. For example, with the relative risk set at 2, only 130 or 170 cases are required when the “minor allele frequency” is 0.4 and 0.2, respectively. We therefore think …" @default.
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• W2615706473 date "2005-10-01" @default.
• W2615706473 modified "2023-09-26" @default.
• W2615706473 title "Assessing the validity of genetic association studies." @default.
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