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Using case‐control designs for genome‐wide screening for associations between genetic markers and disease susceptibility loci
Author(s) -
Yang Quanhe,
Khoury Muin J.,
Atkinson Michael,
Sun Fengzhu,
Cheng Rong,
Flanders W. Dana
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.13701707128
Subject(s) - genetics , allele , linkage disequilibrium , locus (genetics) , biology , odds ratio , genetic marker , population , genetic association , confidence interval , case control study , genotype , gene , haplotype , single nucleotide polymorphism , medicine , environmental health
Abstract We used a case‐control design to scan the genome for any associations between genetic markers and disease susceptibility loci using the first two replicates of the Mycenaean population from the GAW11 (Problem 2) data. Using a case‐control approach, we constructed a series of 2‐by‐3 tables for each allele of every marker on all six chromosomes. Odds ratios (ORs) and 95% confidence intervals (95% CI) were estimated for all alleles of every marker. We selected the one allele for which the estimated OR had the minimum p‐value to plot in the graph. Among these selected ORs, we calculated 95% CI for those that had a p‐value ≤ adjusted α level. Significantly high ORs were taken to indicate an association between a marker locus and a suspected disease‐susceptibility gene. For the Mycenaean population, the case‐control design identified allele number 1 of marker 24 on chromosome 1 to be associated with a disease susceptibility gene, OR = 2.10 (95% CI 1.66–2.62). Our approach failed to show any other significant association between case‐control status and genetic markers. Stratified analysis on the environmental risk factor (E1) provided no further evidence of significant association other than allele 1 of marker 24 on chromosome 1. These data indicate the absence of linkage disequilibrium for markers flanking loci A, B, and C. Finally, we examined the effect of gene×environment (G×E) interaction for the identified allele. Our results provided no evidence of G×E interaction, but suggested that the environmental exposure alone was a risk factor for the disease.