Design considerations in a sib-pair study of linkage for susceptibility loci in cancer

BMC Medical Genetics

Table 6 Comparison of two-point vs. multipoint linkage scores under various non-null simulation conditions.

Simulation Model	Marker Interval	Z _c	Z _p	Z _mc	Z _mp
No Heterogeneity ^a	5 cM	3.26	3.24	3.62	3.60
	10 cM	2.94	2.91	2.85	3.36
	20 cM	2.36	2.30	2.14	2.52
Locus Heterogeneity^b	5 cM	3.10	3.08	3.75	3.53
	10 cM	2.76	2.70	2.72	3.13
	20 cM	2.05	2.01	1.91	2.23
Marker Heterogeneity – Mild^c	5 cM	2.80	2.72	3.57	3.24
	10 cM	2.62	2.54	2.59	2.99
	20 cM	2.22	2.13	2.14	2.35
Marker Heterogeneity- Severe^d	5 cM	2.10	1.95	2.61	2.35
	10 cM	1.70	1.56	1.49	1.86
	20 cM	1.42	1.27	1.18	1.33

All simulations employed 20 replicates of 500 families with 2 affected and 2 unaffected sibs, all sibs typed, no parents or children typed.
^a Baseline risk of 0.018, a relative risk to carriers of 20, allele frequency of 0.003, with a lifetime penetrance of 0.27, no genetic heterogeneity.
^b Baseline risk of 0.018, a relative risk to carriers of 20, allele frequency of 0.003, with a lifetime penetrance of 0.27, and a less common (allele frequency 0.001), equally penetrant unlinked predisposition syndrome.
^c Two populations modeled in an 80%/20% mixture: 1) marker allele frequencies for all markers [0.25,0.25,0.25,0.25], disease allele 0.00325; 2) marker alleles [0.4,0.3,0.2,0.1], disease allele 0.002.
^d Two populations modeled in an 80%/20% mixture: 1) marker allele frequencies for all markers [0.25,0.25,0.25,0.25], disease allele 0.0035; 2) marker alleles [0.4,0.3,0.2,0.1], disease allele 0.001.

ISSN: 1471-2350