[Competing risks of death and Hardy-Weinberg equilibrium in case-control studies of gene-disease association].
OBJECTIVE
To study the impact of competing risks on Hardy-Weinberg equilibrium and their consequences in case-control studies of gene-late onset disease association.


METHODS
Based on a population born in Hardy-Weinberg equilibrium for a particular gene, the genetic composition when the gene is associated with a lethal early-onset disease and its consequences on a late-onset disease can be deduced. Odds ratios estimates are unbiased in case-control studies when controls are sampled by density, even if the controls are in Hardy-Weinberg disequilibrium.


RESULTS
An example in which a mutant gene is associated with early mortality is presented, producing a departure from Hardy-Weinberg equilibrium; as a result, controls in later ages are in disequilibrium, producing an odds ratio equal to 1.61.


CONCLUSIONS
Although the main causes of Hardy-Weinberg disequilibrium in controls are selection bias or genotyping error, a competing risk of death associated with the mutant gene would also result in Hardy-Weinberg disequilibrium among controls.
Llorca
Javier
J
Medicina Preventiva y Salud Pública, Facultad de Medicina, Universidad de Cantabria, Santander, Spain. llorcaj@unican.es
Prieto-Salceda
Dolores
D
Combarros
Onofre
O
Dierssen-Sotos
Trinidad
T
Berciano
José
J
D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics; D016022:Case-Control Studies; D030342:Genetic Diseases, Inborn / Q000235:genetics* / Q000401:mortality*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics*; D008957:Models, Genetic; D009154:Mutation; D016017:Odds Ratio; D015983:Selection Bias