Family studies also permit the investigation of parent-of-origin-specific effects, as have been reported for structural variants62,63. If not properly accounted for, such effects could mask associations and diminish the proportion of heritability explained. High-density SNP data in extended pedigrees can be used to localize predisposition genes, as unexpectedly long runs of identity-by-state sharing among affected relatives suggest true IBD that is probably due to an underlying genetic cause64. Linkage data can also enhance the power of high-density GWA scans by essentially relaxing P-value thresholds in the few instances in which suggestive findings overlap but are not definitive65. Family studies may also be useful in identifying gene–gene interactions, because affected relatives are more likely to share two nearby epistatic loci in linkage disequilibrium that would be unlinked in unrelated individuals66,67.
