Up to this point we considered only families consisting of trios. Our method extends to more general family-based designs. Larger pedigrees can be split into trios. When one or more parent is not genotyped, transmissions can be inferred, provided a sufficient number of relatives have been sampled [38]. When families include multiple affected siblings, the contributions of multiple transmissions are independent if there are no disease loci in the region under examination. Nonindependence due to linkage is usually handled using a robust Huber–White variance estimation [39, 40]. This method makes an empirical adjustment to the variance/covariance matrix of the parameter estimate to account for the correlation among siblings [41-43].
