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Genetic dissection of a complex trait
Author(s) -
Lin Jennifer H.,
Hinrichs Anthony,
Liu KuangYu,
Bierut Laura,
Suarez Brian K.
Publication year - 1999
Publication title -
genetic epidemiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.301
H-Index - 98
eISSN - 1098-2272
pISSN - 0741-0395
DOI - 10.1002/gepi.13701707103
Subject(s) - linkage disequilibrium , biology , genetics , allele , contingency table , transmission disequilibrium test , trait , population , quantitative trait locus , phenotype , linkage (software) , genetic association , genetic linkage , disequilibrium , genetic heterogeneity , genotype , evolutionary biology , gene , haplotype , single nucleotide polymorphism , statistics , demography , mathematics , medicine , computer science , programming language , sociology , ophthalmology
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×environment interaction. Logistic analysis designed to clarify the relationship between disease phenotype and two risk factors (El 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.