Genetic dissection of a complex trait.
A number of genetic and statistical tools were applied to various partitions of the simulated data to identify susceptibility loci, relevant environmental factors, and their interaction(s). The distribution of genotypes at D1G24 among affected children in the first population was found to differ significantly from Hardy-Weinberg expectation. Two transmission/disequilibrium tests identified the preferential transmission of allele 1 as the source of the disequilibrium. Simple contingency table analysis revealed a positive association between exposure to environmental factor E1 and disease phenotype. Multipoint linkage analyses on various subsets of the data identified three "signal" regions (in addition to the aforementioned D1G24) localized at D1G9-10, D3G45, and D5G38. The even numbered chromosomes appeared to be devoid of susceptibility loci. Further analyses of subsamples of affected sib pairs, selected according to their disease phenotype and their exposure to E1, clarified some linkage relationships, particularly for D3G45, thereby suggesting the presence of a specific gene x environment interaction. Logistic analysis designed to clarify the relationship between disease phenotype and two risk factors (E1 exposure and the presence of allele 1 at D1G24) in the first population, revealed a significantly negative interaction which, upon learning the details of the generating model, we now attribute to the presence of heterogeneity.
Lin
J H
JH
Division of Biostatistics, Washington University School of Medicine, St. Louis, MO 63110, USA.
Hinrichs
A
A
Liu
K Y
KY
Bierut
L
L
Suarez
B K
BK
D004777:Environment; D008040:Genetic Linkage; D005820:Genetic Testing; D006801:Humans; D016013:Likelihood Functions; D015810:Linkage Disequilibrium; D008957:Models, Genetic; D010641:Phenotype; D012984:Software