For linkage analysis, a variance components approach was used to calculate multipoint LOD scores at 1 cM intervals across the genome using SOLAR v2.0.4 (Almasy and Blangero, 1998; S.F.B.R, 2009). Variance components linkage analysis assumes that phenotypes are normally distributed, and violations of this assumption can result in inflated LOD scores. To protect against this possibility, simulations were conducted in which a single genetic locus was simulated under the null hypothesis of no linkage across 50,000 trials to derive empirical p-values. These p-values were used to determine the significance of the reported LOD scores (Blangero et al., 2000).
