Problems of reporting genetic associations with complex outcomes


Colhoun, HM; McKeigue, PM; Smith, GD; (2003) Problems of reporting genetic associations with complex outcomes. Lancet, 361 (9360). pp. 865-872. ISSN 0140-6736 DOI: https://doi.org/10.1016/S0140-6736(03)12715-8

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Abstract

Inability to replicate many results has led to increasing scepticism about the value of simple association study designs for detection of genetic variants contributing to common complex traits. Much attention has been drawn to the problems that might, in theory, bedevil this approach, including confounding from population structure, misclassification of outcome, and allelic heterogeneity. Other researchers have argued that absence of replication may indicate true heterogeneity in gene-disease associations. We suggest that the most important factors underlying inability to replicate these associations are publication bias, failure to attribute results to chance, and inadequate sample sizes, problems that are all rectifiable. Without changes to present practice, we risk wastage of scientific effort and rejection of a potentially useful research strategy.

Item Type: Article
Keywords: Alpha-adducin gene, converting enzyme gene, linkage, disequilibrium, essential-hypertension, blood-pressure, population stratification, myocardial-infarction, japanese, population, common disease, human genome, Alleles, Coronary Disease, genetics, Genetics, Population, Human, Polymorphism (Genetics), Publication Bias, Research Design, Variation (Genetics), genetics
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Non-Communicable Disease Epidemiology
PubMed ID: 12642066
Web of Science ID: 181466600027
URI: http://researchonline.lshtm.ac.uk/id/eprint/16792

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