Identification of susceptibility loci contributing to a complex disease using conventional segregation, linkage, and association methods.
We set out to apply conventional analytic methods to a GAW data set of nuclear families with an oligogenic disease that has a population prevalence of 0.023. We chose methods generally applied to disorders with at least one major gene. Our approaches included: 1) complex segregation analysis under two models of ascertainment, 2) linkage analysis assuming either a single-locus trait with possible genetic heterogeneity or a two-locus trait, and 3) allelic association studies using both a case/control approach and the haplotype relative risk (HRR) test. The association study was the only analysis of the three that provided evidence for genes playing a role in the etiology of this disorder.
Falk
C T
CT
Laboratory of Population Genetics, New York Blood Center, NY 10021, USA.
Ashley
A
A
Lamb
N
N
Sherman
S L
SL
D000483:Alleles; D016022:Case-Control Studies; D002874:Chromosome Mapping / Q000379:methods*; D002878:Chromosomes, Human, Pair 1; D002895:Chromosomes, Human, Pair 5; D005260:Female; D005808:Genes, Recessive; D030342:Genetic Diseases, Inborn / Q000453:epidemiology / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D006239:Haplotypes; D006801:Humans; D008126:Lod Score; D008297:Male; D008957:Models, Genetic; D015995:Prevalence; D018570:Risk Assessment