IMPROVEMENT OF THE POWER TO DETECT COMPLEX DISEASE GENES BY REGIONAL INFERENCE PROCEDURES

Theoretical studies and simulations suggest that ''true'' linkage peak s are longer than ''false'' peaks of the same significance level. Our goal for this study was to improve the power oflinkage detection by us ing a regional criterion for linkage; that is, requiring more than one p-value in a given region to pass a threshold. We tested this method by determining the power and type I error for finding the underlying l oci on chromosomes 5 and 8 that contribute to the variability of Q1 (a fter adjusting Q1 for covariates). We used the Haseman-Elston sib-pair statistic to test for linkage of all 367 markers to the adjusted Q1 t rait in 100 replicates. We compared the regional inference procedure t o that of the Lander and Kruglyak (LK) criteria for significant and su ggestive linkage. For example, the power to detect the chromosome 5 lo cus was 48% for the LK criterion for significant linkage (p less than or equal to 0.0001) and 63% when we required two p-values out of five consecutive ones to be less than or equal to 0.001. The type I error w as not more than 5% for either method (2% for the LK and 5% for our cr iterion). This suggests that using a criterion based on length may imp rove the power oflinkage detection for complex traits. (C) 1997 Wiley- Liss, Inc.