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The analysis had four main steps, and parameters were estimated with the method of maximum likelihood using SAS PROC MIXED, version 9.1 (SAS Institute Inc ,Cary, NC).
The population recombination parameter was estimated with the method of Hudson and Kaplan [ 101] based on the minimum number of recombination events in a sample (RM) using DnaSP v. 5.10.00 [ 94].
Frequency of null alleles per locus and population was estimated with the method of Brookfield [ 38] as implemented in Micro-Checker v.2.2.3 [ 61], which does not require detecting null allele homozygotes.
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We estimate with the method of moments the most likely values of αN and βN given the variant frequencies at each marker site.
In contrast to George et al. [ 34] who used a Monte-Carlo method, the gametic IBD matrix was estimated with the recursive method of Pong-Wong et al., [ 35] (software available on request from the author), which uses the closest fully informative or phase-known flanking marker to estimate the IBD at the putative QTL.
The survival curves of recurrences were estimated with the Kaplan Meier method, and the significance of differences between survival rates, for patients with different genotypes and endocrine treatment, was assessed by log-rank test.
The diffusion coefficient of the protein, Dprot, was estimated with the Hydropro method, 49) as the sum of the diffusion coefficient of the two domains, setting the temperature to 298.15 K, the viscosity to that of water at 298.15 K (0.890 cP), and the bead radii of the protein to 3.2 Å.
Estimated with the Kaplan Meier method, after 10 years of follow-up 68% of patients were still alive (overall survival).
This agrees with the method of Firth (1993) which eliminates first-order bias in parameter estimates, with the method of Clogg et al.
The lower precision in all population parameters when estimated with the CC method is because only 50% of the data were used in this analysis.
Both OS and LFS were estimated with the Kaplan Meier method and comparisons among subgroups of patients were performed using the log-rank test.
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