Association studies in consanguineous populations.
To study the genetic determinism of multifactorial diseases in large panmictic populations, a strategy consists in looking for an association with markers closely linked to candidate genes. A distribution of marker genotypes different in patients and controls may indicate that the candidate gene is involved in the disease. In panmictic populations, the power to detect the role of a candidate gene depends on the gametic disequilibrium with the marker locus. In consanguineous populations, we show that it depends on the inbreeding coefficient F as well. Inbreeding increases the power to detect the role of a recessive or quasi-recessive disease-susceptibility factor. The gain in power turns out to be greater for small values of the gametic disequilibrium. Moreover, even in the absence of gametic disequilibrium, the presence of inbreeding may allow to detect the role of a recessive factor. Ignoring inbreeding when it exists may lead to reject falsely a recessive model if the mode of inheritance is inferred on the distribution of genotypes among patients.
Génin
E
E
INSERM U 155 and Insitut National d'Etudes Démographiques, Paris, France.
Clerget-Darpoux
F
F
D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003241:Consanguinity; D004198:Disease Susceptibility; D005260:Female; D005787:Gene Frequency; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D008040:Genetic Linkage; D005819:Genetic Markers; D005828:Genetics, Population; D005838:Genotype; D006801:Humans; D008297:Male; D011336:Probability
D005819:Genetic Markers