TY - JOUR
T1 - Evaluation of candidate genes in case-control studies
T2 - A statistical method to account for related subjects
AU - Slager, S. L.
AU - Schaid, D. J.
N1 - Funding Information:
This research was supported by the United States Public Health Service, National Institutes of Health contract grant number DE13276.
PY - 2001
Y1 - 2001
N2 - Traditional case-control studies provide a powerful and efficient method for evaluation of association between candidate genes and disease. The sampling of cases from multiplex pedigrees, rather than from a catchment area, can increase the likelihood that genetic cases are selected. However, use of all the related cases without accounting for their biological relationship can increase the type I error rate of the statistical test. To overcome this problem, we present an analysis method that is used to compare genotype frequencies between cases and controls, according to a trend in proportions as the dosage of the risk allele increases. This method uses the appropriate variance to account for the correlated family data, thus maintaining the correct type I error rate. The magnitude of the association is estimated by the odds ratio, with the variance of the odds ratio also accounting for the correlated data. Our method makes efficient use of data collected from multiplex families and should prove useful for the analysis of candidate genes among families sampled for linkage studies. An application of our method, to family data from a prostate cancer study, is presented to illustrate the method's utility.
AB - Traditional case-control studies provide a powerful and efficient method for evaluation of association between candidate genes and disease. The sampling of cases from multiplex pedigrees, rather than from a catchment area, can increase the likelihood that genetic cases are selected. However, use of all the related cases without accounting for their biological relationship can increase the type I error rate of the statistical test. To overcome this problem, we present an analysis method that is used to compare genotype frequencies between cases and controls, according to a trend in proportions as the dosage of the risk allele increases. This method uses the appropriate variance to account for the correlated family data, thus maintaining the correct type I error rate. The magnitude of the association is estimated by the odds ratio, with the variance of the odds ratio also accounting for the correlated data. Our method makes efficient use of data collected from multiplex families and should prove useful for the analysis of candidate genes among families sampled for linkage studies. An application of our method, to family data from a prostate cancer study, is presented to illustrate the method's utility.
UR - http://www.scopus.com/inward/record.url?scp=0034994415&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034994415&partnerID=8YFLogxK
U2 - 10.1086/320608
DO - 10.1086/320608
M3 - Article
C2 - 11353403
AN - SCOPUS:0034994415
SN - 0002-9297
VL - 68
SP - 1457
EP - 1462
JO - American journal of human genetics
JF - American journal of human genetics
IS - 6
ER -