title: Problems of reporting genetic associations with complex outcomes.
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.
authors.affiliation: Department of Epidemiology and Public Health, University College London, WC1E 6BT, London, UK. h.colhoun@public-health.ucl.ac.uk
authors.forename: Helen M
authors.initials: HM
authors.lastname: Colhoun
authors.forename: Paul M
authors.initials: PM
authors.lastname: McKeigue
authors.forename: George
authors.initials: G
authors.lastname: Davey Smith
mesh_terms: D000483:Alleles; D003327:Coronary Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D005828:Genetics, Population; D006801:Humans; D011110:Polymorphism, Genetic; D017594:Publication Bias; D012107:Research Design