Linkage analysis involving high densities of markers, where clusters of markers are in linkage disequilibrium (LD), can falsely inflate the evidence for genetic sharing among siblings when neither parent is genotyped 4. To alleviate these concerns, we analyzed a pruned set of 16,311 highly polymorphic, high-quality autosomal SNPs which were filtered to remove any instances in which two nearby markers were correlated with r2>0.1, providing a marker density of ~0.25cM (see Methods). In this analysis of 878 families, four genomic regions showed LOD scores in excess of 2.0 and one region, 20p13, exceeded the formal genome-wide significance threshold of 3.6 5 (maximum LOD, 3.81; Figure 1a, Supplementary Table 2). Restricting analysis to only those families with both parents genotyped (784 families) showed that these results are not an artifact of missing parental data (Figure 1b). We further tested the stability of these results by varying the recombination map and halving the marker density by placing every other marker into two non-overlapping SNP sets (Methods Summary); all analyses showed consistent and strong linkage to the same regions (data not shown).
